Chronic stable angina treatment anti-lipid agents: Difference between revisions

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__NOTOC__
{{Chronic stable angina}}
{{Chronic stable angina}}


'''Editor-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:mgibson@perfuse.org] Phone:617-632-7753;  '''Associate Editor(s)-In-Chief:''' [[Lakshmi Gopalakrishnan|Lakshmi Gopalakrishnan, M.B.B.S.]]
'''Editor-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com] Phone:617-632-7753;  '''Associate Editor(s)-In-Chief:''' [[Lakshmi Gopalakrishnan|Lakshmi Gopalakrishnan, M.B.B.S.]]


==Overview==
==Overview==
[[Statins]] by inhibiting [[HMG-CoA reductase]] subsequently reduce serum cholesterol levels and have been shown to be effective in the primary prevention of various [[Hyperlipidemia|hyperlipidemias]] and secondary prevention of [[ischemic heart disease]].<ref name="pmid7968073"> (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=7968073 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)] ''Lancet'' 344 (8934):1383-9. PMID: [http://pubmed.gov/7968073 7968073]</ref><ref name="pmid16214597">Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16214597 Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.] ''Lancet'' 366 (9493):1267-78. [http://dx.doi.org/10.1016/S0140-6736(05)67394-1 DOI:10.1016/S0140-6736(05)67394-1] PMID: [http://pubmed.gov/16214597 16214597]</ref> The most commonly used statins are [[simvastatin]], [[atorvastatin]], [[pravastatin]] and [[rosuvastatin]]. The incidence of major cardiovascular mortality was '''reduced by 30%''' with the use of [[simvastatin]]<ref name="pmid7968073"> (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=7968073 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)] ''Lancet'' 344 (8934):1383-9. PMID: [http://pubmed.gov/7968073 7968073]</ref> and [[pravastatin]]<ref name="pmid11034935">Sacks FM, Tonkin AM, Shepherd J, Braunwald E, Cobbe S, Hawkins CM et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11034935 Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project.] ''Circulation'' 102 (16):1893-900. PMID: [http://pubmed.gov/11034935 11034935]</ref><ref name="pmid9841303"> (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9841303 Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group.] ''N Engl J Med'' 339 (19):1349-57. [http://dx.doi.org/10.1056/NEJM199811053391902 DOI:10.1056/NEJM199811053391902] PMID: [http://pubmed.gov/9841303 9841303]</ref> in patients with [[coronary artery disease]] and therefore may be used for both primary and secondary prevention.<ref name="pmid15358046">Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15358046 Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.] ''J Am Coll Cardiol'' 44 (3):720-32. [http://dx.doi.org/10.1016/j.jacc.2004.07.001 DOI:10.1016/j.jacc.2004.07.001] PMID: [http://pubmed.gov/15358046 15358046]</ref><ref name="pmid11277825">Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11277825 Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.] ''JAMA'' 285 (13):1711-8. PMID: [http://pubmed.gov/11277825 11277825]</ref><ref name="pmid12686036">Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12686036 Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.] ''Lancet'' 361 (9364):1149-58. [http://dx.doi.org/10.1016/S0140-6736(03)12948-0 DOI:10.1016/S0140-6736(03)12948-0] PMID: [http://pubmed.gov/12686036 12686036]</ref><ref name="pmid15755765">LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15755765 Intensive lipid lowering with atorvastatin in patients with stable coronary disease.] ''N Engl J Med'' 352 (14):1425-35. [http://dx.doi.org/10.1056/NEJMoa050461 DOI:10.1056/NEJMoa050461] PMID: [http://pubmed.gov/15755765 15755765]</ref> However, there are no trials specifically performed on patients with stable angina but they form a significant portion in other major trials studying the efficacy of lipid-lowering drugs on the overall mortality from cardiovascular events.<ref name="pmid12114036">Heart Protection Study Collaborative Group (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12114036 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.] ''Lancet'' 360 (9326):7-22. [http://dx.doi.org/10.1016/S0140-6736(02)09327-3 DOI:10.1016/S0140-6736(02)09327-3] PMID: [http://pubmed.gov/12114036 12114036]</ref> In patients with [[HDL|low HDL]] and [[triglyceride|high triglycerides]] as an adjunctive to [[statin|statin therapy]], [[Fibrate|fibrates]] or [[niacin]] may be used.<ref name="pmid12716814">Robins SJ, Rubins HB, Faas FH, Schaefer EJ, Elam MB, Anderson JW et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12716814 Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT).] ''Diabetes Care'' 26 (5):1513-7. PMID: [http://pubmed.gov/12716814 12716814]</ref>  
[[Statins]] by inhibiting [[HMG-CoA reductase]] subsequently reduce serum cholesterol levels and have been shown to be effective in the primary prevention of various [[Hyperlipidemia|hyperlipidemias]] and secondary prevention of [[ischemic heart disease]].<ref name="pmid7968073"> (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=7968073 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)] ''Lancet'' 344 (8934):1383-9. PMID: [http://pubmed.gov/7968073 7968073]</ref><ref name="pmid16214597">Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16214597 Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.] ''Lancet'' 366 (9493):1267-78. [http://dx.doi.org/10.1016/S0140-6736(05)67394-1 DOI:10.1016/S0140-6736(05)67394-1] PMID: [http://pubmed.gov/16214597 16214597]</ref> The most commonly used statins are [[simvastatin]], [[atorvastatin]], [[pravastatin]] and [[rosuvastatin]]. The incidence of major cardiovascular mortality was reduced by 30% with the use of [[simvastatin]]<ref name="pmid7968073"> (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=7968073 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)] ''Lancet'' 344 (8934):1383-9. PMID: [http://pubmed.gov/7968073 7968073]</ref> and [[pravastatin]]<ref name="pmid11034935">Sacks FM, Tonkin AM, Shepherd J, Braunwald E, Cobbe S, Hawkins CM et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11034935 Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project.] ''Circulation'' 102 (16):1893-900. PMID: [http://pubmed.gov/11034935 11034935]</ref><ref name="pmid9841303"> (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9841303 Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group.] ''N Engl J Med'' 339 (19):1349-57. [http://dx.doi.org/10.1056/NEJM199811053391902 DOI:10.1056/NEJM199811053391902] PMID: [http://pubmed.gov/9841303 9841303]</ref> in patients with [[coronary artery disease]] and therefore may be used for both primary and secondary prevention.<ref name="pmid15358046">Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15358046 Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.] ''J Am Coll Cardiol'' 44 (3):720-32. [http://dx.doi.org/10.1016/j.jacc.2004.07.001 DOI:10.1016/j.jacc.2004.07.001] PMID: [http://pubmed.gov/15358046 15358046]</ref><ref name="pmid11277825">Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11277825 Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.] ''JAMA'' 285 (13):1711-8. PMID: [http://pubmed.gov/11277825 11277825]</ref><ref name="pmid12686036">Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12686036 Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.] ''Lancet'' 361 (9364):1149-58. [http://dx.doi.org/10.1016/S0140-6736(03)12948-0 DOI:10.1016/S0140-6736(03)12948-0] PMID: [http://pubmed.gov/12686036 12686036]</ref><ref name="pmid15755765">LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15755765 Intensive lipid lowering with atorvastatin in patients with stable coronary disease.] ''N Engl J Med'' 352 (14):1425-35. [http://dx.doi.org/10.1056/NEJMoa050461 DOI:10.1056/NEJMoa050461] PMID: [http://pubmed.gov/15755765 15755765]</ref> However, there are no trials specifically performed on patients with stable angina but they form a significant portion in other major trials studying the efficacy of lipid-lowering drugs on the overall mortality from cardiovascular events.<ref name="pmid12114036">Heart Protection Study Collaborative Group (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12114036 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.] ''Lancet'' 360 (9326):7-22. [http://dx.doi.org/10.1016/S0140-6736(02)09327-3 DOI:10.1016/S0140-6736(02)09327-3] PMID: [http://pubmed.gov/12114036 12114036]</ref> In patients with [[HDL|low HDL]] and [[triglyceride|high triglycerides]] as an adjunctive to [[statin|statin therapy]], [[Fibrate|fibrates]] or [[niacin]] may be used.<ref name="pmid12716814">Robins SJ, Rubins HB, Faas FH, Schaefer EJ, Elam MB, Anderson JW et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12716814 Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT).] ''Diabetes Care'' 26 (5):1513-7. PMID: [http://pubmed.gov/12716814 12716814]</ref>  


==Mechanisms of benefit==
==Anti-lipid Agents==
*[[Statins]] competitively inhibit [[HMG-CoA reductase]] that is the rate-limiting enzyme of cholesterol synthesis and hence reduce intracellular cholesterol levels, subsequently, leading to '''increased clearance of serum [[LDL]]'''.<ref name="pmid3464957">Ma PT, Gil G, Südhof TC, Bilheimer DW, Goldstein JL, Brown MS (1986) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3464957 Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits.] ''Proc Natl Acad Sci U S A'' 83 (21):8370-4. PMID: [http://pubmed.gov/3464957 3464957]</ref> <ref name="pmid15358046">Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15358046 Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.] ''J Am Coll Cardiol'' 44 (3):720-32. [http://dx.doi.org/10.1016/j.jacc.2004.07.001 DOI:10.1016/j.jacc.2004.07.001] PMID: [http://pubmed.gov/15358046 15358046]</ref>
===Mechanisms of Benefit===
*[[Statins]] competitively inhibit [[HMG-CoA reductase]] that is the rate-limiting enzyme of cholesterol synthesis and hence reduce intracellular cholesterol levels, subsequently, leading to increased clearance of serum [[LDL]].<ref name="pmid3464957">Ma PT, Gil G, Südhof TC, Bilheimer DW, Goldstein JL, Brown MS (1986) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3464957 Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits.] ''Proc Natl Acad Sci U S A'' 83 (21):8370-4. PMID: [http://pubmed.gov/3464957 3464957]</ref><ref name="pmid15358046">Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15358046 Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.] ''J Am Coll Cardiol'' 44 (3):720-32. [http://dx.doi.org/10.1016/j.jacc.2004.07.001 DOI:10.1016/j.jacc.2004.07.001] PMID: [http://pubmed.gov/15358046 15358046]</ref>


*Direct evidence of statin-based cholesterol lowering effect on [[atherosclerosis]] was presented in the ASTEROID trial, which demonstrated reduction in [[LDL|LDL-C]] with accompanied significant increase in [[HDL-C]] and subsequently resulting in the '''regression of [[atherosclerosis|atheroma]]''' in patients with [[coronary artery disease]].<ref name="pmid16533939">Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM et al. (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16533939 Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial.] ''JAMA'' 295 (13):1556-65. [http://dx.doi.org/10.1001/jama.295.13.jpc60002 DOI:10.1001/jama.295.13.jpc60002] PMID: [http://pubmed.gov/16533939 16533939]</ref>
*Direct evidence of statin-based cholesterol lowering effect on [[atherosclerosis]] was presented in the ''ASTEROID trial'', which demonstrated reduction in [[LDL|LDL-C]] with accompanied significant increase in [[HDL-C]] and subsequently resulting in the regression of [[atherosclerosis|atheroma]] in patients with [[coronary artery disease]].<ref name="pmid16533939">Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM et al. (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16533939 Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial.] ''JAMA'' 295 (13):1556-65. [http://dx.doi.org/10.1001/jama.295.13.jpc60002 DOI:10.1001/jama.295.13.jpc60002] PMID: [http://pubmed.gov/16533939 16533939]</ref>


*It has been postulated that [[statins]] have '''anti-inflammatory''' and '''anti-thrombotic''' effects.<ref name="pmid10523396">Faggiotto A, Paoletti R (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10523396 State-of-the-Art lecture. Statins and blockers of the renin-angiotensin system: vascular protection beyond their primary mode of action.] ''Hypertension'' 34 (4 Pt 2):987-96. PMID: [http://pubmed.gov/10523396 10523396]</ref> <ref name="pmid12590901">Bonetti PO, Lerman LO, Napoli C, Lerman A (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12590901 Statin effects beyond lipid lowering--are they clinically relevant?] ''Eur Heart J'' 24 (3):225-48. PMID: [http://pubmed.gov/12590901 12590901]</ref> <ref name="pmid9613915">Rosenson RS, Tangney CC (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9613915 Antiatherothrombotic properties of statins: implications for cardiovascular event reduction.] ''JAMA'' 279 (20):1643-50. PMID: [http://pubmed.gov/9613915 9613915]</ref> <ref name="pmid15635109">Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15635109 C-reactive protein levels and outcomes after statin therapy.] ''N Engl J Med'' 352 (1):20-8. [http://dx.doi.org/10.1056/NEJMoa042378 DOI:10.1056/NEJMoa042378] PMID: [http://pubmed.gov/15635109 15635109]</ref>
*It has been postulated that [[statins]] have anti-inflammatory and anti-thrombotic effects.<ref name="pmid10523396">Faggiotto A, Paoletti R (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10523396 State-of-the-Art lecture. Statins and blockers of the renin-angiotensin system: vascular protection beyond their primary mode of action.] ''Hypertension'' 34 (4 Pt 2):987-96. PMID: [http://pubmed.gov/10523396 10523396]</ref><ref name="pmid12590901">Bonetti PO, Lerman LO, Napoli C, Lerman A (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12590901 Statin effects beyond lipid lowering--are they clinically relevant?] ''Eur Heart J'' 24 (3):225-48. PMID: [http://pubmed.gov/12590901 12590901]</ref><ref name="pmid9613915">Rosenson RS, Tangney CC (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9613915 Antiatherothrombotic properties of statins: implications for cardiovascular event reduction.] ''JAMA'' 279 (20):1643-50. PMID: [http://pubmed.gov/9613915 9613915]</ref><ref name="pmid15635109">Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15635109 C-reactive protein levels and outcomes after statin therapy.] ''N Engl J Med'' 352 (1):20-8. [http://dx.doi.org/10.1056/NEJMoa042378 DOI:10.1056/NEJMoa042378] PMID: [http://pubmed.gov/15635109 15635109]</ref>


*'''Non-lipid related properties''' of statins might be modulated by interference with isoprenoid synthesis or specific actions of some statins that block cell adhesion receptors and subsequently help to prevent [[atherosclerosis]] via:<ref name="pmid9892578">Furberg CD (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9892578 Natural statins and stroke risk.] ''Circulation'' 99 (2):185-8. PMID: [http://pubmed.gov/9892578 9892578]</ref>
*Non-lipid related properties of statins might be modulated by interference with isoprenoid synthesis or specific actions of some statins that block cell adhesion receptors and subsequently help to prevent [[atherosclerosis]] via:<ref name="pmid9892578">Furberg CD (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9892578 Natural statins and stroke risk.] ''Circulation'' 99 (2):185-8. PMID: [http://pubmed.gov/9892578 9892578]</ref>
:*improving endothelial function,
:*improving endothelial function,
:*modulate inflammatory responses,
:*modulate inflammatory responses,
Line 19: Line 21:
:*increase [[nitric oxide]] bioavailability.
:*increase [[nitric oxide]] bioavailability.


*The non-lipid properties of statins have shown to provide myocardial protection and hence lower the risk of procedural myocardial injury in elective coronary intervention. Such '''short-term myocardial protection''' is achieved by pre-treatment with [[atorvastatin]] 40mg/day for 7 days.<ref name="pmid15277322">Pasceri V, Patti G, Nusca A, Pristipino C, Richichi G, Di Sciascio G et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15277322 Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention: results from the ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) study.] ''Circulation'' 110 (6):674-8. [http://dx.doi.org/10.1161/01.CIR.0000137828.06205.87 DOI:10.1161/01.CIR.0000137828.06205.87] PMID: [http://pubmed.gov/15277322 15277322]</ref>
*The non-lipid properties of statins have shown to provide myocardial protection and hence lower the risk of procedural myocardial injury in elective coronary intervention. Such short-term myocardial protection is achieved by pre-treatment with [[atorvastatin]] 40mg/day for 7 days.<ref name="pmid15277322">Pasceri V, Patti G, Nusca A, Pristipino C, Richichi G, Di Sciascio G et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15277322 Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention: results from the ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) study.] ''Circulation'' 110 (6):674-8. [http://dx.doi.org/10.1161/01.CIR.0000137828.06205.87 DOI:10.1161/01.CIR.0000137828.06205.87] PMID: [http://pubmed.gov/15277322 15277322]</ref>


*Long-term statin therapy have shown to reduce major cardiovascular events such as [[MI]], [[stroke]], and risk of [[revascularization]] in patients with different serum cholesterol levels.<ref name="pmid11034935">Sacks FM, Tonkin AM, Shepherd J, Braunwald E, Cobbe S, Hawkins CM et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11034935 Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project.] ''Circulation'' 102 (16):1893-900. PMID: [http://pubmed.gov/11034935 11034935]</ref> <ref name="pmid12114036">Heart Protection Study Collaborative Group (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12114036 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.] ''Lancet'' 360 (9326):7-22. [http://dx.doi.org/10.1016/S0140-6736(02)09327-3 DOI:10.1016/S0140-6736(02)09327-3] PMID: [http://pubmed.gov/12114036 12114036]</ref> <ref name="pmid15325833">Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15325833 Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.] ''Lancet'' 364 (9435):685-96. [http://dx.doi.org/10.1016/S0140-6736(04)16895-5 DOI:10.1016/S0140-6736(04)16895-5] PMID: [http://pubmed.gov/15325833 15325833]</ref>
*Long-term statin therapy have shown to reduce major cardiovascular events such as [[MI]], [[stroke]], and risk of [[revascularization]] in patients with different serum cholesterol levels.<ref name="pmid11034935">Sacks FM, Tonkin AM, Shepherd J, Braunwald E, Cobbe S, Hawkins CM et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11034935 Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project.] ''Circulation'' 102 (16):1893-900. PMID: [http://pubmed.gov/11034935 11034935]</ref><ref name="pmid12114036">Heart Protection Study Collaborative Group (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12114036 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.] ''Lancet'' 360 (9326):7-22. [http://dx.doi.org/10.1016/S0140-6736(02)09327-3 DOI:10.1016/S0140-6736(02)09327-3] PMID: [http://pubmed.gov/12114036 12114036]</ref><ref name="pmid15325833">Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15325833 Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.] ''Lancet'' 364 (9435):685-96. [http://dx.doi.org/10.1016/S0140-6736(04)16895-5 DOI:10.1016/S0140-6736(04)16895-5] PMID: [http://pubmed.gov/15325833 15325833]</ref>


*Population-based cohort analysis, reported in patients with [[atherosclerosis]], the use of statins have been associated with a reduction in the risk of subsequent [[sepsis]].<ref name="pmid16458766">Hackam DG, Mamdani M, Li P, Redelmeier DA (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16458766 Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis.] ''Lancet'' 367 (9508):413-8. [http://dx.doi.org/10.1016/S0140-6736(06)68041-0 DOI:10.1016/S0140-6736(06)68041-0] PMID: [http://pubmed.gov/16458766 16458766]</ref>
*Population-based cohort analysis, reported in patients with [[atherosclerosis]], the use of statins have been associated with a reduction in the risk of subsequent [[sepsis]].<ref name="pmid16458766">Hackam DG, Mamdani M, Li P, Redelmeier DA (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16458766 Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis.] ''Lancet'' 367 (9508):413-8. [http://dx.doi.org/10.1016/S0140-6736(06)68041-0 DOI:10.1016/S0140-6736(06)68041-0] PMID: [http://pubmed.gov/16458766 16458766]</ref>


*[[Torcetrapib]], by inhibiting cholesteryl ester transfer protein (CETP), '''markedly increases [[HDL|HDL-C]]''' levels and also decreases [[LDL|LDL-C]] levels, both when administered as monotherapy and when used concomitantly with [[statins]] and hence, may be effective in treating patients with [[HDL|low HDL]] levels.<ref name="pmid15071125">Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15071125 Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol.] ''N Engl J Med'' 350 (15):1505-15. [http://dx.doi.org/10.1056/NEJMoa031766 DOI:10.1056/NEJMoa031766] PMID: [http://pubmed.gov/15071125 15071125]</ref><ref name="pmid17387129">Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17387129 Effect of torcetrapib on the progression of coronary atherosclerosis.] ''N Engl J Med'' 356 (13):1304-16. [http://dx.doi.org/10.1056/NEJMoa070635 DOI:10.1056/NEJMoa070635] PMID: [http://pubmed.gov/17387129 17387129]</ref><ref name="pmid17630038">Bots ML, Visseren FL, Evans GW, Riley WA, Revkin JH, Tegeler CH et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17630038 Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial.] ''Lancet'' 370 (9582):153-60. [http://dx.doi.org/10.1016/S0140-6736(07)61088-5 DOI:10.1016/S0140-6736(07)61088-5] PMID: [http://pubmed.gov/17630038 17630038]</ref>
*[[Torcetrapib]], by inhibiting cholesteryl ester transfer protein (CETP), markedly increases [[HDL|HDL-C]] levels and also decreases [[LDL|LDL-C]] levels, both when administered as monotherapy and when used concomitantly with [[statins]] and hence, may be effective in treating patients with [[HDL|low HDL]] levels.<ref name="pmid15071125">Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15071125 Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol.] ''N Engl J Med'' 350 (15):1505-15. [http://dx.doi.org/10.1056/NEJMoa031766 DOI:10.1056/NEJMoa031766] PMID: [http://pubmed.gov/15071125 15071125]</ref><ref name="pmid17387129">Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17387129 Effect of torcetrapib on the progression of coronary atherosclerosis.] ''N Engl J Med'' 356 (13):1304-16. [http://dx.doi.org/10.1056/NEJMoa070635 DOI:10.1056/NEJMoa070635] PMID: [http://pubmed.gov/17387129 17387129]</ref><ref name="pmid17630038">Bots ML, Visseren FL, Evans GW, Riley WA, Revkin JH, Tegeler CH et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17630038 Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial.] ''Lancet'' 370 (9582):153-60. [http://dx.doi.org/10.1016/S0140-6736(07)61088-5 DOI:10.1016/S0140-6736(07)61088-5] PMID: [http://pubmed.gov/17630038 17630038]</ref>


==Indications==
===Indications===
*In all patients with [[coronary artery disease]], statins are indicated both for primary and secondary prevention, irrespective of the serum cholesterol concentrations, owing to its property of reducing over-all cardiovascular mortality.<ref name="pmid11034935">Sacks FM, Tonkin AM, Shepherd J, Braunwald E, Cobbe S, Hawkins CM et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11034935 Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project.] ''Circulation'' 102 (16):1893-900. PMID: [http://pubmed.gov/11034935 11034935]</ref><ref name="pmid15358046">Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15358046 Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.] ''J Am Coll Cardiol'' 44 (3):720-32. [http://dx.doi.org/10.1016/j.jacc.2004.07.001 DOI:10.1016/j.jacc.2004.07.001] PMID: [http://pubmed.gov/15358046 15358046]</ref><ref name="pmid12114036">Heart Protection Study Collaborative Group (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12114036 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.] ''Lancet'' 360 (9326):7-22. [http://dx.doi.org/10.1016/S0140-6736(02)09327-3 DOI:10.1016/S0140-6736(02)09327-3] PMID: [http://pubmed.gov/12114036 12114036]</ref><ref name="pmid15325833">Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15325833 Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.] ''Lancet'' 364 (9435):685-96. [http://dx.doi.org/10.1016/S0140-6736(04)16895-5 DOI:10.1016/S0140-6736(04)16895-5] PMID: [http://pubmed.gov/15325833 15325833]</ref><ref name="pmid16214597">Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16214597 Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.] ''Lancet'' 366 (9493):1267-78. [http://dx.doi.org/10.1016/S0140-6736(05)67394-1 DOI:10.1016/S0140-6736(05)67394-1] PMID: [http://pubmed.gov/16214597 16214597]</ref>
*In all patients with [[coronary artery disease]], statins are indicated both for primary and secondary prevention, irrespective of the serum cholesterol concentrations, owing to its property of reducing over-all cardiovascular mortality.<ref name="pmid11034935">Sacks FM, Tonkin AM, Shepherd J, Braunwald E, Cobbe S, Hawkins CM et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11034935 Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project.] ''Circulation'' 102 (16):1893-900. PMID: [http://pubmed.gov/11034935 11034935]</ref><ref name="pmid15358046">Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15358046 Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.] ''J Am Coll Cardiol'' 44 (3):720-32. [http://dx.doi.org/10.1016/j.jacc.2004.07.001 DOI:10.1016/j.jacc.2004.07.001] PMID: [http://pubmed.gov/15358046 15358046]</ref><ref name="pmid12114036">Heart Protection Study Collaborative Group (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12114036 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.] ''Lancet'' 360 (9326):7-22. [http://dx.doi.org/10.1016/S0140-6736(02)09327-3 DOI:10.1016/S0140-6736(02)09327-3] PMID: [http://pubmed.gov/12114036 12114036]</ref><ref name="pmid15325833">Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15325833 Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.] ''Lancet'' 364 (9435):685-96. [http://dx.doi.org/10.1016/S0140-6736(04)16895-5 DOI:10.1016/S0140-6736(04)16895-5] PMID: [http://pubmed.gov/15325833 15325833]</ref><ref name="pmid16214597">Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16214597 Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.] ''Lancet'' 366 (9493):1267-78. [http://dx.doi.org/10.1016/S0140-6736(05)67394-1 DOI:10.1016/S0140-6736(05)67394-1] PMID: [http://pubmed.gov/16214597 16214597]</ref>


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*[[Fibrate|Fibrates]] are also beneficial in patients with [[diabetes]] or [[Syndrome X|metabolic syndrome X]].<ref name="pmid12716814">Robins SJ, Rubins HB, Faas FH, Schaefer EJ, Elam MB, Anderson JW et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12716814 Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT).] ''Diabetes Care'' 26 (5):1513-7. PMID: [http://pubmed.gov/12716814 12716814]</ref>  
*[[Fibrate|Fibrates]] are also beneficial in patients with [[diabetes]] or [[Syndrome X|metabolic syndrome X]].<ref name="pmid12716814">Robins SJ, Rubins HB, Faas FH, Schaefer EJ, Elam MB, Anderson JW et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12716814 Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT).] ''Diabetes Care'' 26 (5):1513-7. PMID: [http://pubmed.gov/12716814 12716814]</ref>  


==Contra-indications==
===Contraindications===
All [[statins]] are contra-indicated in pregnancy and breastfeeding. Use of statin during early pregnancy has been associated to cause congenital anomalies in the fetus.
All [[statins]] are contra-indicated in pregnancy and breastfeeding. Use of statin during early pregnancy has been associated to cause congenital anomalies in the fetus.


==Drug interactions==
===Drug Interactions===
Concomitant use of [[fibrate|Fibrates]], antibiotics (such as [[Clarithromycin|clarithromycin]] and [[Erythromycin|erythromycin]]), anti-fungals (such as [[ketaconazole]] and [[itraconazole]] with any of the [[statins]], increases the risk of [[myopathy]] and subsequent [[rhabdomyolysis]].<ref name="pmid15572716">Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15572716 Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs.] ''JAMA'' 292 (21):2585-90. [http://dx.doi.org/10.1001/jama.292.21.2585 DOI:10.1001/jama.292.21.2585] PMID: [http://pubmed.gov/15572716 15572716]</ref><ref name="pmid12386136">Prueksaritanont T, Tang C, Qiu Y, Mu L, Subramanian R, Lin JH (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12386136 Effects of fibrates on metabolism of statins in human hepatocytes.] ''Drug Metab Dispos'' 30 (11):1280-7. PMID: [http://pubmed.gov/12386136 12386136]</ref> However, the use of [[fenofibrate]] has not shown to interfere with the catabolism of [[pravastatin]], hence is less likely to increase the risk of [[myopathy]] when used in concomitantly with statins.<ref name="pmid10709162">Pan WJ, Gustavson LE, Achari R, Rieser MJ, Ye X, Gutterman C et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10709162 Lack of a clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers.] ''J Clin Pharmacol'' 40 (3):316-23. PMID: [http://pubmed.gov/10709162 10709162]</ref>
Concomitant use of [[fibrate|Fibrates]], antibiotics (such as [[Clarithromycin|clarithromycin]] and [[Erythromycin|erythromycin]]), anti-fungals (such as [[ketaconazole]] and [[itraconazole]] with any of the [[statins]], increases the risk of [[myopathy]] and subsequent [[rhabdomyolysis]].<ref name="pmid15572716">Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15572716 Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs.] ''JAMA'' 292 (21):2585-90. [http://dx.doi.org/10.1001/jama.292.21.2585 DOI:10.1001/jama.292.21.2585] PMID: [http://pubmed.gov/15572716 15572716]</ref><ref name="pmid12386136">Prueksaritanont T, Tang C, Qiu Y, Mu L, Subramanian R, Lin JH (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12386136 Effects of fibrates on metabolism of statins in human hepatocytes.] ''Drug Metab Dispos'' 30 (11):1280-7. PMID: [http://pubmed.gov/12386136 12386136]</ref> However, the use of [[fenofibrate]] has not shown to interfere with the catabolism of [[pravastatin]], hence is less likely to increase the risk of [[myopathy]] when used in concomitantly with statins.<ref name="pmid10709162">Pan WJ, Gustavson LE, Achari R, Rieser MJ, Ye X, Gutterman C et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10709162 Lack of a clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers.] ''J Clin Pharmacol'' 40 (3):316-23. PMID: [http://pubmed.gov/10709162 10709162]</ref>


==Dosage==
===Dosage===
*In patients with stable angina, an intensive lipid-lowering therapy with [[atorvastatin]] 80 mg/day has shown to provide significant clinical benefit and improve prognosis. However, this occurred with a greater incidence of elevated aminotransferase levels ''(from 0.2 to 1.2%;p<0.001)''.<ref name="pmid15755765">LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15755765 Intensive lipid lowering with atorvastatin in patients with stable coronary disease.] ''N Engl J Med'' 352 (14):1425-35. [http://dx.doi.org/10.1056/NEJMoa050461 DOI:10.1056/NEJMoa050461] PMID: [http://pubmed.gov/15755765 15755765]</ref><ref name="pmid16287954">Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16287954 High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial.] ''JAMA'' 294 (19):2437-45. [http://dx.doi.org/10.1001/jama.294.19.2437 DOI:10.1001/jama.294.19.2437] PMID: [http://pubmed.gov/16287954 16287954]</ref>
*In patients with stable angina, an intensive lipid-lowering therapy with [[atorvastatin]] 80 mg/day has shown to provide significant clinical benefit and improve prognosis. However, this occurred with a greater incidence of elevated aminotransferase levels (from 0.2 to 1.2%;p<0.001).<ref name="pmid15755765">LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15755765 Intensive lipid lowering with atorvastatin in patients with stable coronary disease.] ''N Engl J Med'' 352 (14):1425-35. [http://dx.doi.org/10.1056/NEJMoa050461 DOI:10.1056/NEJMoa050461] PMID: [http://pubmed.gov/15755765 15755765]</ref><ref name="pmid16287954">Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16287954 High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial.] ''JAMA'' 294 (19):2437-45. [http://dx.doi.org/10.1001/jama.294.19.2437 DOI:10.1001/jama.294.19.2437] PMID: [http://pubmed.gov/16287954 16287954]</ref>


*Dose reduction of [[statin]] with the addition of cholesterol absorption inhibitor such as [[ezetimibe]] is indicated when adequate lipid control is not achieved with the highest [[statin]] dose or wherein [[statins]] are poorly tolerated.<ref name="pmid14627172">Wierzbicki AS (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14627172 Ezetimibe: a new addition to lipid-lowering therapy.] ''Int J Clin Pract'' 57 (8):653-5. PMID: [http://pubmed.gov/14627172 14627172]</ref>
*Dose reduction of [[statin]] with the addition of cholesterol absorption inhibitor such as [[ezetimibe]] is indicated when adequate lipid control is not achieved with the highest [[statin]] dose or wherein [[statins]] are poorly tolerated.<ref name="pmid14627172">Wierzbicki AS (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14627172 Ezetimibe: a new addition to lipid-lowering therapy.] ''Int J Clin Pract'' 57 (8):653-5. PMID: [http://pubmed.gov/14627172 14627172]</ref>


==Adverse effects==
===Adverse Effects===
*[[Rhabdomyolysis]].<ref name="pmid15572716">Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15572716 Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs.] ''JAMA'' 292 (21):2585-90. [http://dx.doi.org/10.1001/jama.292.21.2585 DOI:10.1001/jama.292.21.2585] PMID: [http://pubmed.gov/15572716 15572716]</ref>
*[[Rhabdomyolysis]].<ref name="pmid15572716">Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15572716 Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs.] ''JAMA'' 292 (21):2585-90. [http://dx.doi.org/10.1001/jama.292.21.2585 DOI:10.1001/jama.292.21.2585] PMID: [http://pubmed.gov/15572716 15572716]</ref>


*High dose [[atorvastatin]] is associated with greater incidence of elevated aminotransferases. Hence, [[LFT|liver function tests]] should be regularly monitored.<ref name="pmid15755765">LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15755765 Intensive lipid lowering with atorvastatin in patients with stable coronary disease.] ''N Engl J Med'' 352 (14):1425-35. [http://dx.doi.org/10.1056/NEJMoa050461 DOI:10.1056/NEJMoa050461] PMID: [http://pubmed.gov/15755765 15755765]</ref>
*High dose [[atorvastatin]] is associated with greater incidence of elevated aminotransferases. Hence, [[LFT|liver function tests]] should be regularly monitored.<ref name="pmid15755765">LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15755765 Intensive lipid lowering with atorvastatin in patients with stable coronary disease.] ''N Engl J Med'' 352 (14):1425-35. [http://dx.doi.org/10.1056/NEJMoa050461 DOI:10.1056/NEJMoa050461] PMID: [http://pubmed.gov/15755765 15755765]</ref>


*In patients undergoing [[CABG|coronary bypass surgery]], '''peri-operative statin withdrawal''' have been associated with increased frequency of cardiac events.<ref name="pmid17631090">Schouten O, Hoeks SE, Welten GM, Davignon J, Kastelein JJ, Vidakovic R et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17631090 Effect of statin withdrawal on frequency of cardiac events after vascular surgery.] ''Am J Cardiol'' 100 (2):316-20. [http://dx.doi.org/10.1016/j.amjcard.2007.02.093 DOI:10.1016/j.amjcard.2007.02.093] PMID: [http://pubmed.gov/17631090 17631090]</ref>
*In patients undergoing [[CABG|coronary bypass surgery]], peri-operative statin withdrawal have been associated with increased frequency of cardiac events.<ref name="pmid17631090">Schouten O, Hoeks SE, Welten GM, Davignon J, Kastelein JJ, Vidakovic R et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17631090 Effect of statin withdrawal on frequency of cardiac events after vascular surgery.] ''Am J Cardiol'' 100 (2):316-20. [http://dx.doi.org/10.1016/j.amjcard.2007.02.093 DOI:10.1016/j.amjcard.2007.02.093] PMID: [http://pubmed.gov/17631090 17631090]</ref>


==Supportive trial data==
===Supportive Trial Data===
*In the '''Scandinavian Simvastatin Survival Study (4S)''', 4444 patients with [[coronary heart disease]] were randomized to a double-blind treatment of either, simvastatin or placebo. The goal of the study was to assess the effect of [[simvastatin]] on mortality and morbidity. Researchers reported that there was a 30% relative risk reduction in mortality from all cardiovascular causes with the use of simvastatin.<ref name="pmid7968073"> (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=7968073 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)] ''Lancet'' 344 (8934):1383-9. PMID: [http://pubmed.gov/7968073 7968073]</ref>
*In the ''Scandinavian Simvastatin Survival Study (4S)'', 4444 patients with [[coronary heart disease]] were randomized to a double-blind treatment of either, simvastatin or placebo. The goal of the study was to assess the effect of [[simvastatin]] on mortality and morbidity. Researchers reported that there was a 30% relative risk reduction in mortality from all cardiovascular causes with the use of simvastatin.<ref name="pmid7968073"> (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=7968073 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)] ''Lancet'' 344 (8934):1383-9. PMID: [http://pubmed.gov/7968073 7968073]</ref>


*In the '''ASCOT-LLA trial''', 19,342 patients, aged 40-79 years, who reported at least three cardiovascular risk factors were randomized to receive one of two antihypertensive regimens, [[atorvastatin]] or placebo. The purpose of this study was to assess the benefit of [[atorvastatin]] in the prevention of coronary and stroke events amongst [[hypertension|hypertensive]] patients with a total cholesteroal of ≤6.5 mmol/L. The primary endpoint from total cardiovascular events ''(389 atorvastatin vs 486 placebo, 0.79 [0.69-0.90], p=0.0005)'', total coronary events ''(178 vs 247, 0.71 [0.59-0.86], p=0.0005)'' and stroke ''(89 vs 121, 0.73 [0.56-0.96], p=0.024)'', during a median follow-up of 3.3 years, was significantly reduced with [[atorvastatin]].<ref name="pmid12686036">Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12686036 Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.] ''Lancet'' 361 (9364):1149-58. [http://dx.doi.org/10.1016/S0140-6736(03)12948-0 DOI:10.1016/S0140-6736(03)12948-0] PMID: [http://pubmed.gov/12686036 12686036]</ref>  
*In the ''ASCOT-LLA'' trial, 19,342 patients, aged 40-79 years, who reported at least three cardiovascular risk factors were randomized to receive one of two antihypertensive regimens, [[atorvastatin]] or placebo. The purpose of this study was to assess the benefit of [[atorvastatin]] in the prevention of coronary and stroke events amongst [[hypertension|hypertensive]] patients with a total cholesteroal of ≤6.5 mmol/L. The primary endpoint from total cardiovascular events (389 atorvastatin vs 486 placebo, 0.79 [0.69-0.90], p=0.0005), total coronary events (178 vs 247, 0.71 [0.59-0.86], p=0.0005) and stroke (89 vs 121, 0.73 [0.56-0.96], p=0.024), during a median follow-up of 3.3 years, was significantly reduced with [[atorvastatin]].<ref name="pmid12686036">Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12686036 Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.] ''Lancet'' 361 (9364):1149-58. [http://dx.doi.org/10.1016/S0140-6736(03)12948-0 DOI:10.1016/S0140-6736(03)12948-0] PMID: [http://pubmed.gov/12686036 12686036]</ref>  


*In the '''Heart Protection Study''', 20,536 patients, aged 40-80 years, with [[coronary artery disease]], other occlusive arterial disease, or [[diabetes]] were randomized to receive either, [[simvastatin]] or placebo. The goal of the study was to assess the effect of [[simvastatin]] on mortality. Researchers observed that adding simvastatin reduced the rates of [[MI]] ''(8.7% vs 11.8; p<0.0001)'', [[stroke]] ''(4.3% vs 5.7%; p<0.0001)'' and [[revascularization]] ''(9.1% vs 11.7%; p<0.0001)''. The annual excess risk of [[myopathy]] was about 0.01%.<ref name="pmid12114036">Heart Protection Study Collaborative Group (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12114036 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.] ''Lancet'' 360 (9326):7-22. [http://dx.doi.org/10.1016/S0140-6736(02)09327-3 DOI:10.1016/S0140-6736(02)09327-3] PMID: [http://pubmed.gov/12114036 12114036]</ref>
*In the ''Heart Protection'' Study, 20,536 patients, aged 40-80 years, with [[coronary artery disease]], other occlusive arterial disease, or [[diabetes]] were randomized to receive either, [[simvastatin]] or placebo. The goal of the study was to assess the effect of [[simvastatin]] on mortality. Researchers observed that adding simvastatin reduced the rates of [[MI]] (8.7% vs 11.8; p<0.0001), [[stroke]] (4.3% vs 5.7%; p<0.0001) and [[revascularization]] (9.1% vs 11.7%; p<0.0001). The annual excess risk of [[myopathy]] was about 0.01%.<ref name="pmid12114036">Heart Protection Study Collaborative Group (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12114036 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.] ''Lancet'' 360 (9326):7-22. [http://dx.doi.org/10.1016/S0140-6736(02)09327-3 DOI:10.1016/S0140-6736(02)09327-3] PMID: [http://pubmed.gov/12114036 12114036]</ref>


*In the '''ASTEROID trial''', which assessed the effect of intensive [[statin|statin therapy]] on the progression atherosclerosis, demonstrated that use of very high-intensity statin therapy resulted in significant regression of [[atherosclerosis]].<ref name="pmid16533939">Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM et al. (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16533939 Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial.] ''JAMA'' 295 (13):1556-65. [http://dx.doi.org/10.1001/jama.295.13.jpc60002 DOI:10.1001/jama.295.13.jpc60002] PMID: [http://pubmed.gov/16533939 16533939]</ref>
*In the ''ASTEROID'' trial, which assessed the effect of intensive [[statin|statin therapy]] on the progression atherosclerosis, demonstrated that use of very high-intensity statin therapy resulted in significant regression of [[atherosclerosis]].<ref name="pmid16533939">Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM et al. (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16533939 Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial.] ''JAMA'' 295 (13):1556-65. [http://dx.doi.org/10.1001/jama.295.13.jpc60002 DOI:10.1001/jama.295.13.jpc60002] PMID: [http://pubmed.gov/16533939 16533939]</ref>


*A '''prospective meta-analysis''' reviewed 14 randomized trials, involving 90,056 patients, to assess the effect of statin therapy on different clinical outcomes, per 1.0 mmol/L reduction in [[LDL|LDL cholesterol]] during a mean follow-up of 5 years. Researchers observed that within the primary endpoint data there was a 12% proportional reduction in all-cause mortality, per mmol/L reduction, in [[LDL|LDL cholesterol]]. This was found in conjunction with a 19% significant reduction in coronary mortality and corresponding reductions in [[myocardial infarction]] or coronary death, in the need for [[revascularization|coronary revascularization]] and in fatal or non-fatal [[stroke]]. Thus, the study concluded that in high-risk patients, prolong [[statin|statin therapy]] with substantial [[LDL|LDL-C]] reduction subsequently reduced the 5-year incidence of incidence of major coronary events, [[revascularization|coronary revascularization]], and [[stroke]].<ref name="pmid16214597">Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16214597 Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.] ''Lancet'' 366 (9493):1267-78. [http://dx.doi.org/10.1016/S0140-6736(05)67394-1 DOI:10.1016/S0140-6736(05)67394-1] PMID: [http://pubmed.gov/16214597 16214597]</ref>
*A prospective meta-analysis reviewed 14 randomized trials, involving 90,056 patients, to assess the effect of statin therapy on different clinical outcomes, per 1.0 mmol/L reduction in [[LDL|LDL cholesterol]] during a mean follow-up of 5 years. Researchers observed that within the primary endpoint data there was a 12% proportional reduction in all-cause mortality, per mmol/L reduction, in [[LDL|LDL cholesterol]]. This was found in conjunction with a 19% significant reduction in coronary mortality and corresponding reductions in [[myocardial infarction]] or coronary death, in the need for [[revascularization|coronary revascularization]] and in fatal or non-fatal [[stroke]]. Thus, the study concluded that in high-risk patients, prolong [[statin|statin therapy]] with substantial [[LDL|LDL-C]] reduction subsequently reduced the 5-year incidence of incidence of major coronary events, [[revascularization|coronary revascularization]], and [[stroke]].<ref name="pmid16214597">Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16214597 Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.] ''Lancet'' 366 (9493):1267-78. [http://dx.doi.org/10.1016/S0140-6736(05)67394-1 DOI:10.1016/S0140-6736(05)67394-1] PMID: [http://pubmed.gov/16214597 16214597]</ref>


*A '''meta-analysis''' reviewed 97 randomized controlled trials to assess the efficacy and safety of various lipid-lowering interventions and compared their impact on the overall cardiovascular mortality. The risk ratios for overall mortality in comparison to control group, was 0.87 for [[statins]], 1.00 for [[Fibrate|fibrates]], 0.84 for [[resins]], 0.96 for [[niacin]], 0.77 for n-3 fatty acids, and 0.97 for diet, while the risk ratios for cardiac mortality indicated a significant benefit from [[statins]] ''(0.78; 95% CI, 0.72-0.84)'', resins ''(0.70; 95% CI, 0.50-0.99)'' and n-3 fatty acids ''(0.68; 95% CI, 0.52-0.90)''. Thus, the study concluded [[statins]] and n-3 fatty acids provided better outcomes by reducing the risk of mortality and also concluded that any potential reduction in cardiac mortality from [[Fibrate|fibrates]] was counterbalanced by an increased risk of death from non-cardiovascular causes.<ref name="pmid15824290">Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15824290 Effect of different antilipidemic agents and diets on mortality: a systematic review.] ''Arch Intern Med'' 165 (7):725-30. [http://dx.doi.org/10.1001/archinte.165.7.725 DOI:10.1001/archinte.165.7.725] PMID: [http://pubmed.gov/15824290 15824290]</ref>
*A meta-analysis reviewed 97 randomized controlled trials to assess the efficacy and safety of various lipid-lowering interventions and compared their impact on the overall cardiovascular mortality. The risk ratios for overall mortality in comparison to control group, was 0.87 for [[statins]], 1.00 for [[Fibrate|fibrates]], 0.84 for [[resins]], 0.96 for [[niacin]], 0.77 for n-3 fatty acids, and 0.97 for diet, while the risk ratios for cardiac mortality indicated a significant benefit from [[statins]] (0.78; 95% CI, 0.72-0.84), resins (0.70; 95% CI, 0.50-0.99) and n-3 fatty acids (0.68; 95% CI, 0.52-0.90). Thus, the study concluded [[statins]] and n-3 fatty acids provided better outcomes by reducing the risk of mortality and also concluded that any potential reduction in cardiac mortality from [[Fibrate|fibrates]] was counterbalanced by an increased risk of death from non-cardiovascular causes.<ref name="pmid15824290">Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15824290 Effect of different antilipidemic agents and diets on mortality: a systematic review.] ''Arch Intern Med'' 165 (7):725-30. [http://dx.doi.org/10.1001/archinte.165.7.725 DOI:10.1001/archinte.165.7.725] PMID: [http://pubmed.gov/15824290 15824290]</ref>


*In the '''FIELD study''', that assessed the effect of [[fenofibrate]] on cardiovascular events, involved 9,795 [[diabetic]] patients who were randomized to either fenofibrate or placebo. The study reported no significant reduction in the primary endpoint of coronary death and non-fatal [[MI]], but a reduction in the total cardiovascular events was observed. Hence, the study concluded no significant benefit with the use of fenofibrate.<ref name="pmid16310551">Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16310551 Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial.] ''Lancet'' 366 (9500):1849-61. [http://dx.doi.org/10.1016/S0140-6736(05)67667-2 DOI:10.1016/S0140-6736(05)67667-2] PMID: [http://pubmed.gov/16310551 16310551]</ref>
*In the ''FIELD'' study, that assessed the effect of [[fenofibrate]] on cardiovascular events, involved 9,795 [[diabetic]] patients who were randomized to either fenofibrate or placebo. The study reported no significant reduction in the primary endpoint of coronary death and non-fatal [[MI]], but a reduction in the total cardiovascular events was observed. Hence, the study concluded no significant benefit with the use of fenofibrate.<ref name="pmid16310551">Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16310551 Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial.] ''Lancet'' 366 (9500):1849-61. [http://dx.doi.org/10.1016/S0140-6736(05)67667-2 DOI:10.1016/S0140-6736(05)67667-2] PMID: [http://pubmed.gov/16310551 16310551]</ref>


*In the '''ILLUSTRATE trial''', 1188 [[coronary artery disease]] patients with corrected [[LDL|LDL-C]] level of less than 100 mg/dL achieved with [[atorvastatin]] pre-treatment, who underwent intravascular ultrasonography at baseline, were randomized to receive either a combination of [[torcetrapib]] and [[atorvastatin]] or [[atorvastatin]] alone, to assess the effect of CETP inhibition and [[HDL]] elevation in reducing the progression of [[atherosclerosis]]. At 24-month follow-up,  approximately 61% relative increase in [[HDL|HDL cholesterol]] levels and a 20% relative decrease in [[LDL|LDL cholesterol]] levels with a subsequent [[LDL]]:[[HDL]] ratio of less than 1.0 was observed in the combined torcetrapib-atorvastatin group. However, no significant difference in the change of percent atheroma volume between the 2 groups were observed. Thus, the study concluded that the CETP inhibitor [[torcetrapib]] was associated with a substantial increase in [[HDL|HDL cholesterol]] and decrease in [[LDL|LDL cholesterol]] levels with no significant reduction in the progression of [[atherosclerosis]] and was associated with an [[hypertension|increase in blood pressure]].<ref name="pmid17387129">Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17387129 Effect of torcetrapib on the progression of coronary atherosclerosis.] ''N Engl J Med'' 356 (13):1304-16. [http://dx.doi.org/10.1056/NEJMoa070635 DOI:10.1056/NEJMoa070635] PMID: [http://pubmed.gov/17387129 17387129]</ref>
*In the ''ILLUSTRATE'' trial, 1188 [[coronary artery disease]] patients with corrected [[LDL|LDL-C]] level of less than 100 mg/dL achieved with [[atorvastatin]] pre-treatment, who underwent intravascular ultrasonography at baseline, were randomized to receive either a combination of [[torcetrapib]] and [[atorvastatin]] or [[atorvastatin]] alone, to assess the effect of CETP inhibition and [[HDL]] elevation in reducing the progression of [[atherosclerosis]]. At 24-month follow-up,  approximately 61% relative increase in [[HDL|HDL cholesterol]] levels and a 20% relative decrease in [[LDL|LDL cholesterol]] levels with a subsequent [[LDL]]:[[HDL]] ratio of less than 1.0 was observed in the combined torcetrapib-atorvastatin group. However, no significant difference in the change of percent atheroma volume between the 2 groups were observed. Thus, the study concluded that the CETP inhibitor [[torcetrapib]] was associated with a substantial increase in [[HDL|HDL cholesterol]] and decrease in [[LDL|LDL cholesterol]] levels with no significant reduction in the progression of [[atherosclerosis]] and was associated with an [[hypertension|increase in blood pressure]].<ref name="pmid17387129">Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17387129 Effect of torcetrapib on the progression of coronary atherosclerosis.] ''N Engl J Med'' 356 (13):1304-16. [http://dx.doi.org/10.1056/NEJMoa070635 DOI:10.1056/NEJMoa070635] PMID: [http://pubmed.gov/17387129 17387129]</ref>


*In the '''RADIANCE 2 trial''' to assess the effect of CETP inhibitor, [[torcetrapib]], on [[atherosclerosis|carotid atherosclerosis]] progression involving 752 patients with [[Dyslipidemia|mixed dyslipidemia]] who have [[triglycerides,|high triglycerides]], [[HDL|low HDL-C]] and [[LDL|high LDL-C]] levels. The study reported significant increase in the [[HDL|HDL-C]] levels and decrease in the [[LDL|LDL-C]] levels observed in patients receiving [[torcetrapib]]. However, similar to the ILLUSTRATE trial, no significant reduction in the progression of [[atherosclerosis|carotid atherosclerosis]] with an associated [[hypertension|increase in blood pressure]] was observed.<ref name="pmid17630038">Bots ML, Visseren FL, Evans GW, Riley WA, Revkin JH, Tegeler CH et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17630038 Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial.] ''Lancet'' 370 (9582):153-60. [http://dx.doi.org/10.1016/S0140-6736(07)61088-5 DOI:10.1016/S0140-6736(07)61088-5] PMID: [http://pubmed.gov/17630038 17630038]</ref>
*In the ''RADIANCE 2'' trial to assess the effect of CETP inhibitor, [[torcetrapib]], on [[atherosclerosis|carotid atherosclerosis]] progression involving 752 patients with [[Dyslipidemia|mixed dyslipidemia]] who have [[triglycerides,|high triglycerides]], [[HDL|low HDL-C]] and [[LDL|high LDL-C]] levels. The study reported significant increase in the [[HDL|HDL-C]] levels and decrease in the [[LDL|LDL-C]] levels observed in patients receiving [[torcetrapib]]. However, similar to the ILLUSTRATE trial, no significant reduction in the progression of [[atherosclerosis|carotid atherosclerosis]] with an associated [[hypertension|increase in blood pressure]] was observed.<ref name="pmid17630038">Bots ML, Visseren FL, Evans GW, Riley WA, Revkin JH, Tegeler CH et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17630038 Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial.] ''Lancet'' 370 (9582):153-60. [http://dx.doi.org/10.1016/S0140-6736(07)61088-5 DOI:10.1016/S0140-6736(07)61088-5] PMID: [http://pubmed.gov/17630038 17630038]</ref>


*In the '''ILLUMINATE trial''', 15,067 patients with a high cardiovascular risk were randomized in double-blind study of lipid level management on its impact on clinical cardiovascular events. Patients received either, a potent CETP inhibtor such as [[torcetrapib]] in addition to [[atorvastatin]] or [[atorvastatin]] alone. Premature termination of the study was due to an increased risk of cardiovascular events and death ''(82 deaths observed in the combined therapy group and 51 deaths in patients taking atorvastatin alone)''. Despite, the beneficial effects of significant [[LDL|LDL-cholesterol]] reduction and increase in the [[HDL|HDL cholesterol]] associated with [[torcetrapib]] use, the disadvantage of higher rates of [[MI]], [[revascularization]], [[heart failure]], [[chronic stable angina definition|angina]] are presumably compound-specific.<ref name="pmid18552062">Rensen PC, Jukema JW (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18552062 [Torcetrapib increases mortality in patients with a high risk of cardiovascular disorders].] ''Ned Tijdschr Geneeskd'' 152 (19):1088-90. PMID: [http://pubmed.gov/18552062 18552062]</ref>
*In the ''ILLUMINATE'' trial, 15,067 patients with a high cardiovascular risk were randomized in double-blind study of lipid level management on its impact on clinical cardiovascular events. Patients received either, a potent CETP inhibtor such as [[torcetrapib]] in addition to [[atorvastatin]] or [[atorvastatin]] alone. Premature termination of the study was due to an increased risk of cardiovascular events and death (82 deaths observed in the combined therapy group and 51 deaths in patients taking atorvastatin alone). Despite, the beneficial effects of significant [[LDL|LDL-cholesterol]] reduction and increase in the [[HDL|HDL cholesterol]] associated with [[torcetrapib]] use, the disadvantage of higher rates of [[MI]], [[revascularization]], [[heart failure]], [[chronic stable angina definition|angina]] are presumably compound-specific.<ref name="pmid18552062">Rensen PC, Jukema JW (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18552062 [Torcetrapib increases mortality in patients with a high risk of cardiovascular disorders].] ''Ned Tijdschr Geneeskd'' 152 (19):1088-90. PMID: [http://pubmed.gov/18552062 18552062]</ref>


==ACC/AHA Guidelines- Pharmacotherapy to Prevent MI and Death and Reduce Symptoms (DO NOT EDIT) <ref name="pmid10351980">Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM et al. (1999)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10351980ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: executive summary and recommendations. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina).]''Circulation'' 99 (21):2829-48. PMID: [http://pubmed.gov/10351980 10351980]</ref> <ref name="pmid12515758">Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12515758 ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina).] ''Circulation'' 107 (1):149-58. PMID: [http://pubmed.gov/12515758 12515758]</ref> <ref name="pmid17998462">Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17998462 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.] ''Circulation'' 116 (23):2762-72.[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf] PMID: [http://pubmed.gov/17998462 17998462]</ref>==
==2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines and 2002 Guideline Update for the Management of Patients With Chronic Stable Angina (DO NOT EDIT)<ref name="pmid12515758">Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12515758 ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina).] ''Circulation'' 107 (1):149-58.[http://content.onlinejacc.org/cgi/reprint/41/1/159.pdf] PMID: [http://pubmed.gov/12515758 12515758]</ref><ref name="pmid17998462">Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17998462 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.] ''Circulation'' 116 (23):2762-72.[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf] PMID: [http://pubmed.gov/17998462 17998462]</ref>==
{{cquote|
===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]===
'''1.''' Dietary therapy for all patients should include reduced intake of saturated fats (to less than 7% of total calories), transfatty acids, and cholesterol (to less than 200 mg per day). ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''


'''2.''' Daily [[Chronic stable angina treatment physical activity|physical activity]] and [[Chronic stable angina treatment weight management|weight management]] are recommended for all patients. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
===Lipid Lowering Agents (DO NOT EDIT)<ref name="pmid12515758">Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12515758 ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina).] ''Circulation'' 107 (1):149-58.[http://content.onlinejacc.org/cgi/reprint/41/1/159.pdf] PMID: [http://pubmed.gov/12515758 12515758]</ref><ref name="pmid17998462">Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17998462 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.] ''Circulation'' 116 (23):2762-72.[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf] PMID: [http://pubmed.gov/17998462 17998462]</ref>===


'''3.''' Recommended lipid management includes assessment of a [[Coronary risk profile (patient information)|fasting lipid profile]].
{|class="wikitable"
:'''a.''' [[LDL|LDL-C]] should be less than 100 mg per dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''
|-
:'''b.''' If baseline [[LDL|LDL-C]] is greater than or equal to 100 mg per dL, LDL-lowering drug therapy should be initiated in addition to therapeutic lifestyle changes. When LDL-lowering medications are used in high-risk or moderately high-risk persons, it is recommended that intensity of therapy be sufficient to achieve a 30% to 40% reduction in [[LDL|LDL-C]] levels. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
:'''c.''' If on-treatment [[LDL|LDL-C]] is greater than or equal to 100 mg per dL, LDL-lowering drug therapy should be intensified. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''
|-
:'''d.''' If [[triglycerides|TG]] are 200 to 499 mg per dL, [[HDL|non–HDL-C]] should be less than 130 mg per dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Dietary therapy for all patients should include reduced intake of saturated fats (to less than 7% of total calories), transfatty acids, and cholesterol (to less than 200 mg per day). ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
:'''e.''' If [[triglycerides|TG]] are greater than or equal to 500 mg per dL, therapeutic options to lower the [[triglycerides|TG]] to reduce the risk of [[pancreatitis]] are fibrate or niacin; these should be initiated before [[LDL|LDL-C]] lowering therapy. The goal is to achieve [[HDL|non–HDL-C]] less than 130 mg per dL if possible. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Daily [[Chronic stable angina treatment physical activity|physical activity]] and [[Chronic stable angina treatment weight management|weight management]] are recommended for all patients. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' Recommended lipid management includes assessment of a [[Coronary risk profile (patient information)|fasting lipid profile]]. <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''a.''' [[LDL|LDL-C]] should be less than 100 mg per dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''c.''' If baseline [[LDL|LDL-C]] is greater than or equal to 100 mg per dL, LDL-lowering drug therapy should be initiated in addition to therapeutic lifestyle changes. When LDL-lowering medications are used in high-risk or moderately high-risk persons, it is recommended that intensity of therapy be sufficient to achieve a 30% to 40% reduction in [[LDL|LDL-C]] levels. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''d.''' If on-treatment [[LDL|LDL-C]] is greater than or equal to 100 mg per dL, LDL-lowering drug therapy should be intensified. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''f.''' If [[triglycerides|TG]] are 200 to 499 mg per dL, [[HDL|non–HDL-C]] should be less than 130 mg per dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''i.''' If [[triglycerides|TG]] are greater than or equal to 500 mg per dL, therapeutic options to lower the [[triglycerides|TG]] to reduce the risk of [[pancreatitis]] are fibrate or niacin; these should be initiated before [[LDL|LDL-C]] lowering therapy. The goal is to achieve [[HDL|non–HDL-C]] less than 130 mg per dL if possible. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' Drug combinations are beneficial for patients on lipid lowering therapy who are unable to achieve [[LDL|LDL-C]] less than 100 mg per dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' Lipid-lowering therapy in patients with documented [[CAD]] and [[LDL-LDL cholesterol]] greater than 130 mg/dL with a target [[LDL]] of less than 100 mg/dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|}


'''4.''' Drug combinations are beneficial for patients on lipid
{|class="wikitable"
lowering therapy who are unable to achieve [[LDL|LDL-C]] less
|-
than 100 mg per dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Adding plant stanol or sterols (2 g per day) and/or viscous fiber (greater than 10 g per day) is reasonable to further lower [[LDL|LDL-C]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' Recommended lipid management includes assessment of a [[Coronary risk profile (patient information)|fasting lipid profile]]. <nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''b.''' Reduction of [[LDL|LDL-C]] to less than 70 mg per dL or high-dose statin therapy is reasonable. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''e.''' If baseline [[LDL|LDL-C]] is 70 to 100 mg per dL, it is reasonable to treat LDL-C to less than 70 mg per dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''g.''' Further reduction of [[HDL|non–HDL-C]] to less than 100 mg per dL is reasonable, if [[triglycerides|TG]] are greater than or equal to 200 to 499 mg per dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''h.''' Therapeutic options to reduce [[HDL|non–HDL-C]] are:
*[[Niacin]] can be useful as a therapeutic option to reduce non–HDL-C (after [[LDL|LDL-C]]–lowering therapy) or ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
*[[Fibrate|Fibrate therapy]] as a therapeutic option can be useful to reduce non–HDL-C (after LDL-C–lowering therapy).''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' The following lipid management strategies can be beneficial:  <nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''a.''' If [[LDL|LDL-C]] less than 70 mg per dL is the chosen target, consider drug titration to achieve this level to minimize side effects and cost. When LDL-C less than 70 mg per dL is not achievable because of high baseline LDL-C levels, it generally is possible to achieve reductions of greater than 50% in LDL-C levels by either statins or LDL-C–lowering drug combinations. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''4.''' Lipid-lowering therapy in patients with documented [[CAD]] and [[LDL|LDL cholesterol]] 100 to 129 mg/dL, with a target LDL of 100 mg/dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}


'''5.''' Lipid-lowering therapy in patients with documented [[CAD]] and [[LDL-LDL cholesterol]] greater than 130 mg/dL
{|class="wikitable"
with a target [[LDL]] of less than 100 mg/dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' For all patients, encouraging consumption of omega-3 fatty acids in the form of fish or in capsule form (1 g per day) for risk reduction may be reasonable. For treatment of elevated [[triglyceride|TG]], higher doses are usually necessary for risk reduction. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}


===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]===  
==ESC Guidelines- Pharmacological Therapy to Improve Prognosis in Patients with Stable Angina (DO NOT EDIT)<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367}}</ref>==
'''1.''' Adding plant stanol or sterols (2 g per day) and/or viscous fiber (greater than 10 g per day) is reasonable to further lower [[LDL|LDL-C]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''


'''2.''' Lipid-lowering therapy in patients with documented [[CAD]] and [[LDL|LDL cholesterol]] 100 to 129 mg/dL, with a target LDL of 100 mg/dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
===Lipid Lowering Agents (DO NOT EDIT)<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367}}</ref>===


'''3.''' Recommended lipid management includes assessment of a [[Coronary risk profile (patient information)|fasting lipid profile]].
{| class="wikitable"
:'''a.''' Reduction of [[LDL|LDL-C]] to less than 70 mg per dL or high-dose statin therapy is reasonable. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''
|-
:'''b.''' If baseline [[LDL|LDL-C]] is 70 to 100 mg per dL, it is reasonable to treat LDL-C to less than 70 mg per dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
:'''c.''' Further reduction of [[HDL|non–HDL-C]] to less than 100 mg per dL is reasonable, if [[triglycerides|TG]] are greater than or equal to 200 to 499 mg per dL. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' [[Statin|Statin therapy]] for all patients with [[CAD|coronary disease]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|}


'''4.''' Therapeutic options to reduce [[HDL|non–HDL-C]] are:
{| class="wikitable"
:'''a.''' [[Niacin]] can be useful as a therapeutic option to reduce non–HDL-C (after [[LDL|LDL-C]]–lowering therapy) ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
|-
:'''b.''' [[Fibrate|Fibrate therapy]] as a therapeutic option can be useful to reduce non–HDL-C (after LDL-C–lowering therapy). ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
| colspan="1" style="text-align:center; background:LemonChiffon"| [[European society of cardiology#Classes of Recommendations|Class IIa]]
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[Statin|High dose statin therapy]] in high-risk (more than 2% annual CV mortality) patients with proven [[CAD|coronary disease]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}


'''5.''' The following lipid management strategies can be beneficial:
{| class="wikitable"
:'''a.''' If [[LDL|LDL-C]] less than 70 mg per dL is the chosen target, consider drug titration to achieve this level to minimize side effects and cost. When LDL-C less than 70 mg per dL is not achievable because of high baseline LDL-C levels, it generally is possible to achieve reductions of greater than 50% in LDL-C levels by either statins or LDL-C–lowering drug combinations. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''
|-
 
| colspan="1" style="text-align:center; background:LemonChiffon"| [[European society of cardiology#Classes of Recommendations|Class IIb]]
===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]===
|-
'''1.''' For all patients, encouraging consumption of omega-3 fatty acids in the form of fish or in capsule form (1 g per day) for risk reduction may be reasonable. For treatment of elevated [[triglyceride|TG]], higher doses are usually necessary for risk reduction. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''}}
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[Fibrate|Fibrate therapy]] in patients with [[HDL|low HDL]] and [[Triglycerides|high triglycerides]] who have [[diabetes]] or the [[metabolic syndrome]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
 
|-
==ESC Guidelines- Pharmacological therapy to improve prognosis in patients with stable angina (DO NOT EDIT) <ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367}}</ref>==
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' [[Fibrate]] or [[nicotinic acid]] as adjunctive therapy to statin in patients with low HDL and high triglycerides at high risk (more than 2% annual CV mortality). ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
{{cquote|
|}
===[[European society of cardiology#Classes of Recommendations|Class I]]===
'''1.''' [[Statin|Statin therapy]] for all patients with [[CAD|coronary disease]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''
 
===[[European society of cardiology#Classes of Recommendations|Class IIa]]===
'''1.''' [[Statin|High dose statin therapy]] in high-risk (more than 2% annual CV mortality) patients with proven [[CAD|coronary disease]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''
 
===[[European society of cardiology#Classes of Recommendations|Class IIb]]===
'''1.''' [[Fibrate|Fibrate therapy]] in patients with [[HDL|low HDL]] and [[Triglycerides|high triglycerides]] who have [[diabetes]] or the [[metabolic syndrome]]. ''([[European society of cardiology#Level of Evidence|Level of evidence: B]])''
 
'''2.''' [[Fibrate]] or [[nicotinic acid]] as adjunctive therapy to statin in patients with low HDL and high triglycerides at high risk (more than 2% annual CV mortality). ''([[European society of cardiology#Level of Evidence|Level of evidence: C]])''}}
 
==Vote on and Suggest Revisions to the Current Guidelines==
*[[The Living Guidelines: Chronic Stable Angina Pectoris | The Chronic Stable Angina Living Guidelines: Vote on current recommendations and suggest revisions to the guidelines]]
 
==Guidelines Resources==
*[http://circ.ahajournals.org/content/99/21/2829.full.pdf The ACC/AHA/ACP–ASIM Guidelines for the Management of Patients With Chronic Stable Angina]<ref name="pmid10351980">Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM et al. (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10351980 ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: executive summary and recommendations. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina).] ''Circulation'' 99 (21):2829-48. [http://circ.ahajournals.org/content/99/21/2829.full.pdf] PMID: [http://pubmed.gov/10351980 10351980]</ref>
 
*[http://content.onlinejacc.org/cgi/reprint/41/1/159.pdf The ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina]<ref name="pmid12515758">Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12515758 ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina).] ''Circulation'' 107 (1):149-58.[http://content.onlinejacc.org/cgi/reprint/41/1/159.pdf] PMID: [http://pubmed.gov/12515758 12515758]</ref>
 
*[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf The 2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina]<ref name="pmid17998462">Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17998462 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.] ''Circulation'' 116 (23):2762-72.[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf] PMID: [http://pubmed.gov/17998462 17998462]</ref>
 
*[http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-angina-FT.pdf Guidelines on the management of stable angina pectoris: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology]<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= |url=url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367 [http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-angina-FT.pdf]}} </ref>


==References==
==References==
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{{WikiDoc Sources}}
{{WikiDoc Sources}}


[[Category:Disease]]
[[Category:Ischemic heart diseases]]
[[Category:Ischemic heart diseases]]
[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
[[Category:Intensive care medicine]]
[[Category:Up-To-Date]]
[[Category:Up-To-Date]]
[[Category:Up-To-Date cardiology]]
[[Category:Up-To-Date cardiology]]

Latest revision as of 19:40, 6 February 2013

Chronic stable angina Microchapters

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Chronic stable angina treatment anti-lipid agents On the Web

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3] Phone:617-632-7753; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S.

Overview

Statins by inhibiting HMG-CoA reductase subsequently reduce serum cholesterol levels and have been shown to be effective in the primary prevention of various hyperlipidemias and secondary prevention of ischemic heart disease.[1][2] The most commonly used statins are simvastatin, atorvastatin, pravastatin and rosuvastatin. The incidence of major cardiovascular mortality was reduced by 30% with the use of simvastatin[1] and pravastatin[3][4] in patients with coronary artery disease and therefore may be used for both primary and secondary prevention.[5][6][7][8] However, there are no trials specifically performed on patients with stable angina but they form a significant portion in other major trials studying the efficacy of lipid-lowering drugs on the overall mortality from cardiovascular events.[9] In patients with low HDL and high triglycerides as an adjunctive to statin therapy, fibrates or niacin may be used.[10]

Anti-lipid Agents

Mechanisms of Benefit

  • Statins competitively inhibit HMG-CoA reductase that is the rate-limiting enzyme of cholesterol synthesis and hence reduce intracellular cholesterol levels, subsequently, leading to increased clearance of serum LDL.[11][5]
  • Direct evidence of statin-based cholesterol lowering effect on atherosclerosis was presented in the ASTEROID trial, which demonstrated reduction in LDL-C with accompanied significant increase in HDL-C and subsequently resulting in the regression of atheroma in patients with coronary artery disease.[12]
  • Non-lipid related properties of statins might be modulated by interference with isoprenoid synthesis or specific actions of some statins that block cell adhesion receptors and subsequently help to prevent atherosclerosis via:[17]
  • improving endothelial function,
  • modulate inflammatory responses,
  • maintain plaque stability and prevent thrombus formation,
  • increase nitric oxide bioavailability.
  • The non-lipid properties of statins have shown to provide myocardial protection and hence lower the risk of procedural myocardial injury in elective coronary intervention. Such short-term myocardial protection is achieved by pre-treatment with atorvastatin 40mg/day for 7 days.[18]
  • Long-term statin therapy have shown to reduce major cardiovascular events such as MI, stroke, and risk of revascularization in patients with different serum cholesterol levels.[3][9][19]
  • Population-based cohort analysis, reported in patients with atherosclerosis, the use of statins have been associated with a reduction in the risk of subsequent sepsis.[20]
  • Torcetrapib, by inhibiting cholesteryl ester transfer protein (CETP), markedly increases HDL-C levels and also decreases LDL-C levels, both when administered as monotherapy and when used concomitantly with statins and hence, may be effective in treating patients with low HDL levels.[21][22][23]

Indications

  • In all patients with coronary artery disease, statins are indicated both for primary and secondary prevention, irrespective of the serum cholesterol concentrations, owing to its property of reducing over-all cardiovascular mortality.[3][5][9][19][2]
  • In patients with stable angina, pre-treatment with atorvastatin was associated with the reduction of procedural myocardial injury, as assessed by biochemical markers.[18]
  • Statin therapy in diabetics with vascular disease and in the elderly have demonstrated beneficial effects.[9][24][25][26]

Contraindications

All statins are contra-indicated in pregnancy and breastfeeding. Use of statin during early pregnancy has been associated to cause congenital anomalies in the fetus.

Drug Interactions

Concomitant use of Fibrates, antibiotics (such as clarithromycin and erythromycin), anti-fungals (such as ketaconazole and itraconazole with any of the statins, increases the risk of myopathy and subsequent rhabdomyolysis.[29][30] However, the use of fenofibrate has not shown to interfere with the catabolism of pravastatin, hence is less likely to increase the risk of myopathy when used in concomitantly with statins.[31]

Dosage

  • In patients with stable angina, an intensive lipid-lowering therapy with atorvastatin 80 mg/day has shown to provide significant clinical benefit and improve prognosis. However, this occurred with a greater incidence of elevated aminotransferase levels (from 0.2 to 1.2%;p<0.001).[8][32]
  • Dose reduction of statin with the addition of cholesterol absorption inhibitor such as ezetimibe is indicated when adequate lipid control is not achieved with the highest statin dose or wherein statins are poorly tolerated.[33]

Adverse Effects

  • In patients undergoing coronary bypass surgery, peri-operative statin withdrawal have been associated with increased frequency of cardiac events.[34]

Supportive Trial Data

  • In the Scandinavian Simvastatin Survival Study (4S), 4444 patients with coronary heart disease were randomized to a double-blind treatment of either, simvastatin or placebo. The goal of the study was to assess the effect of simvastatin on mortality and morbidity. Researchers reported that there was a 30% relative risk reduction in mortality from all cardiovascular causes with the use of simvastatin.[1]
  • In the ASCOT-LLA trial, 19,342 patients, aged 40-79 years, who reported at least three cardiovascular risk factors were randomized to receive one of two antihypertensive regimens, atorvastatin or placebo. The purpose of this study was to assess the benefit of atorvastatin in the prevention of coronary and stroke events amongst hypertensive patients with a total cholesteroal of ≤6.5 mmol/L. The primary endpoint from total cardiovascular events (389 atorvastatin vs 486 placebo, 0.79 [0.69-0.90], p=0.0005), total coronary events (178 vs 247, 0.71 [0.59-0.86], p=0.0005) and stroke (89 vs 121, 0.73 [0.56-0.96], p=0.024), during a median follow-up of 3.3 years, was significantly reduced with atorvastatin.[7]
  • In the Heart Protection Study, 20,536 patients, aged 40-80 years, with coronary artery disease, other occlusive arterial disease, or diabetes were randomized to receive either, simvastatin or placebo. The goal of the study was to assess the effect of simvastatin on mortality. Researchers observed that adding simvastatin reduced the rates of MI (8.7% vs 11.8; p<0.0001), stroke (4.3% vs 5.7%; p<0.0001) and revascularization (9.1% vs 11.7%; p<0.0001). The annual excess risk of myopathy was about 0.01%.[9]
  • In the ASTEROID trial, which assessed the effect of intensive statin therapy on the progression atherosclerosis, demonstrated that use of very high-intensity statin therapy resulted in significant regression of atherosclerosis.[12]
  • A prospective meta-analysis reviewed 14 randomized trials, involving 90,056 patients, to assess the effect of statin therapy on different clinical outcomes, per 1.0 mmol/L reduction in LDL cholesterol during a mean follow-up of 5 years. Researchers observed that within the primary endpoint data there was a 12% proportional reduction in all-cause mortality, per mmol/L reduction, in LDL cholesterol. This was found in conjunction with a 19% significant reduction in coronary mortality and corresponding reductions in myocardial infarction or coronary death, in the need for coronary revascularization and in fatal or non-fatal stroke. Thus, the study concluded that in high-risk patients, prolong statin therapy with substantial LDL-C reduction subsequently reduced the 5-year incidence of incidence of major coronary events, coronary revascularization, and stroke.[2]
  • A meta-analysis reviewed 97 randomized controlled trials to assess the efficacy and safety of various lipid-lowering interventions and compared their impact on the overall cardiovascular mortality. The risk ratios for overall mortality in comparison to control group, was 0.87 for statins, 1.00 for fibrates, 0.84 for resins, 0.96 for niacin, 0.77 for n-3 fatty acids, and 0.97 for diet, while the risk ratios for cardiac mortality indicated a significant benefit from statins (0.78; 95% CI, 0.72-0.84), resins (0.70; 95% CI, 0.50-0.99) and n-3 fatty acids (0.68; 95% CI, 0.52-0.90). Thus, the study concluded statins and n-3 fatty acids provided better outcomes by reducing the risk of mortality and also concluded that any potential reduction in cardiac mortality from fibrates was counterbalanced by an increased risk of death from non-cardiovascular causes.[35]
  • In the FIELD study, that assessed the effect of fenofibrate on cardiovascular events, involved 9,795 diabetic patients who were randomized to either fenofibrate or placebo. The study reported no significant reduction in the primary endpoint of coronary death and non-fatal MI, but a reduction in the total cardiovascular events was observed. Hence, the study concluded no significant benefit with the use of fenofibrate.[36]
  • In the ILLUMINATE trial, 15,067 patients with a high cardiovascular risk were randomized in double-blind study of lipid level management on its impact on clinical cardiovascular events. Patients received either, a potent CETP inhibtor such as torcetrapib in addition to atorvastatin or atorvastatin alone. Premature termination of the study was due to an increased risk of cardiovascular events and death (82 deaths observed in the combined therapy group and 51 deaths in patients taking atorvastatin alone). Despite, the beneficial effects of significant LDL-cholesterol reduction and increase in the HDL cholesterol associated with torcetrapib use, the disadvantage of higher rates of MI, revascularization, heart failure, angina are presumably compound-specific.[37]

2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines and 2002 Guideline Update for the Management of Patients With Chronic Stable Angina (DO NOT EDIT)[38][39]

Lipid Lowering Agents (DO NOT EDIT)[38][39]

Class I
"1. Dietary therapy for all patients should include reduced intake of saturated fats (to less than 7% of total calories), transfatty acids, and cholesterol (to less than 200 mg per day). (Level of Evidence: B) "
"2. Daily physical activity and weight management are recommended for all patients. (Level of Evidence: B) "
"3. Recommended lipid management includes assessment of a fasting lipid profile. "
"a. LDL-C should be less than 100 mg per dL. (Level of Evidence: A) "
"c. If baseline LDL-C is greater than or equal to 100 mg per dL, LDL-lowering drug therapy should be initiated in addition to therapeutic lifestyle changes. When LDL-lowering medications are used in high-risk or moderately high-risk persons, it is recommended that intensity of therapy be sufficient to achieve a 30% to 40% reduction in LDL-C levels. (Level of Evidence: A) "
"d. If on-treatment LDL-C is greater than or equal to 100 mg per dL, LDL-lowering drug therapy should be intensified. (Level of Evidence: A) "
"f. If TG are 200 to 499 mg per dL, non–HDL-C should be less than 130 mg per dL. (Level of Evidence: B) "
"i. If TG are greater than or equal to 500 mg per dL, therapeutic options to lower the TG to reduce the risk of pancreatitis are fibrate or niacin; these should be initiated before LDL-C lowering therapy. The goal is to achieve non–HDL-C less than 130 mg per dL if possible. (Level of Evidence: C) "
"4. Drug combinations are beneficial for patients on lipid lowering therapy who are unable to achieve LDL-C less than 100 mg per dL. (Level of Evidence: C) "
"5. Lipid-lowering therapy in patients with documented CAD and LDL-LDL cholesterol greater than 130 mg/dL with a target LDL of less than 100 mg/dL. (Level of Evidence: A) "
Class IIa
"1. Adding plant stanol or sterols (2 g per day) and/or viscous fiber (greater than 10 g per day) is reasonable to further lower LDL-C. (Level of Evidence: B) "
"2. Recommended lipid management includes assessment of a fasting lipid profile. "
"b. Reduction of LDL-C to less than 70 mg per dL or high-dose statin therapy is reasonable. (Level of Evidence: A) "
"e. If baseline LDL-C is 70 to 100 mg per dL, it is reasonable to treat LDL-C to less than 70 mg per dL. (Level of Evidence: B) "
"g. Further reduction of non–HDL-C to less than 100 mg per dL is reasonable, if TG are greater than or equal to 200 to 499 mg per dL. (Level of Evidence: B) "
"h. Therapeutic options to reduce non–HDL-C are:
"3. The following lipid management strategies can be beneficial: "
"a. If LDL-C less than 70 mg per dL is the chosen target, consider drug titration to achieve this level to minimize side effects and cost. When LDL-C less than 70 mg per dL is not achievable because of high baseline LDL-C levels, it generally is possible to achieve reductions of greater than 50% in LDL-C levels by either statins or LDL-C–lowering drug combinations. (Level of Evidence: C) "
"4. Lipid-lowering therapy in patients with documented CAD and LDL cholesterol 100 to 129 mg/dL, with a target LDL of 100 mg/dL. (Level of Evidence: B) "
Class IIb
"1. For all patients, encouraging consumption of omega-3 fatty acids in the form of fish or in capsule form (1 g per day) for risk reduction may be reasonable. For treatment of elevated TG, higher doses are usually necessary for risk reduction. (Level of Evidence: B) "

ESC Guidelines- Pharmacological Therapy to Improve Prognosis in Patients with Stable Angina (DO NOT EDIT)[40]

Lipid Lowering Agents (DO NOT EDIT)[40]

Class I
"1. Statin therapy for all patients with coronary disease. (Level of Evidence: A) "
Class IIa
"1. High dose statin therapy in high-risk (more than 2% annual CV mortality) patients with proven coronary disease. (Level of Evidence: B) "
Class IIb
"1. Fibrate therapy in patients with low HDL and high triglycerides who have diabetes or the metabolic syndrome. (Level of Evidence: B) "
"2. Fibrate or nicotinic acid as adjunctive therapy to statin in patients with low HDL and high triglycerides at high risk (more than 2% annual CV mortality). (Level of Evidence: C) "

References

  1. 1.0 1.1 1.2 (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet 344 (8934):1383-9. PMID: 7968073
  2. 2.0 2.1 2.2 Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C et al. (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366 (9493):1267-78. DOI:10.1016/S0140-6736(05)67394-1 PMID: 16214597
  3. 3.0 3.1 3.2 Sacks FM, Tonkin AM, Shepherd J, Braunwald E, Cobbe S, Hawkins CM et al. (2000) Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project. Circulation 102 (16):1893-900. PMID: 11034935
  4. (1998) Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 339 (19):1349-57. DOI:10.1056/NEJM199811053391902 PMID: 9841303
  5. 5.0 5.1 5.2 Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB et al. (2004) Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol 44 (3):720-32. DOI:10.1016/j.jacc.2004.07.001 PMID: 15358046
  6. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D et al. (2001) Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 285 (13):1711-8. PMID: 11277825
  7. 7.0 7.1 Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M et al. (2003) Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 361 (9364):1149-58. DOI:10.1016/S0140-6736(03)12948-0 PMID: 12686036
  8. 8.0 8.1 8.2 LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC et al. (2005) Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 352 (14):1425-35. DOI:10.1056/NEJMoa050461 PMID: 15755765
  9. 9.0 9.1 9.2 9.3 9.4 Heart Protection Study Collaborative Group (2002) MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360 (9326):7-22. DOI:10.1016/S0140-6736(02)09327-3 PMID: 12114036
  10. 10.0 10.1 Robins SJ, Rubins HB, Faas FH, Schaefer EJ, Elam MB, Anderson JW et al. (2003) Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT). Diabetes Care 26 (5):1513-7. PMID: 12716814
  11. Ma PT, Gil G, Südhof TC, Bilheimer DW, Goldstein JL, Brown MS (1986) Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits. Proc Natl Acad Sci U S A 83 (21):8370-4. PMID: 3464957
  12. 12.0 12.1 Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM et al. (2006) Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 295 (13):1556-65. DOI:10.1001/jama.295.13.jpc60002 PMID: 16533939
  13. Faggiotto A, Paoletti R (1999) State-of-the-Art lecture. Statins and blockers of the renin-angiotensin system: vascular protection beyond their primary mode of action. Hypertension 34 (4 Pt 2):987-96. PMID: 10523396
  14. Bonetti PO, Lerman LO, Napoli C, Lerman A (2003) Statin effects beyond lipid lowering--are they clinically relevant? Eur Heart J 24 (3):225-48. PMID: 12590901
  15. Rosenson RS, Tangney CC (1998) Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 279 (20):1643-50. PMID: 9613915
  16. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH et al. (2005) C-reactive protein levels and outcomes after statin therapy. N Engl J Med 352 (1):20-8. DOI:10.1056/NEJMoa042378 PMID: 15635109
  17. Furberg CD (1999) Natural statins and stroke risk. Circulation 99 (2):185-8. PMID: 9892578
  18. 18.0 18.1 Pasceri V, Patti G, Nusca A, Pristipino C, Richichi G, Di Sciascio G et al. (2004) Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention: results from the ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) study. Circulation 110 (6):674-8. DOI:10.1161/01.CIR.0000137828.06205.87 PMID: 15277322
  19. 19.0 19.1 19.2 Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ et al. (2004) Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 364 (9435):685-96. DOI:10.1016/S0140-6736(04)16895-5 PMID: 15325833
  20. Hackam DG, Mamdani M, Li P, Redelmeier DA (2006) Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis. Lancet 367 (9508):413-8. DOI:10.1016/S0140-6736(06)68041-0 PMID: 16458766
  21. Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW et al. (2004) Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med 350 (15):1505-15. DOI:10.1056/NEJMoa031766 PMID: 15071125
  22. 22.0 22.1 Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT et al. (2007) Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 356 (13):1304-16. DOI:10.1056/NEJMoa070635 PMID: 17387129
  23. 23.0 23.1 Bots ML, Visseren FL, Evans GW, Riley WA, Revkin JH, Tegeler CH et al. (2007) Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet 370 (9582):153-60. DOI:10.1016/S0140-6736(07)61088-5 PMID: 17630038
  24. 24.0 24.1 Collins R, Armitage J, Parish S, Sleigh P, Peto R, Heart Protection Study Collaborative Group (2003) MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 361 (9374):2005-16. PMID: 12814710
  25. Goldberg RB, Mellies MJ, Sacks FM, Moyé LA, Howard BV, Howard WJ et al. (1998) Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators. Circulation 98 (23):2513-9. PMID: 9843456
  26. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM et al. (2002) Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360 (9346):1623-30. PMID: 12457784
  27. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB et al. (1999) Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 341 (6):410-8. DOI:10.1056/NEJM199908053410604 PMID: 10438259
  28. Farnier M (2003) Combination therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative: a critical review of potential benefits and drawbacks. Am J Cardiovasc Drugs 3 (3):169-78. PMID: 14727929
  29. 29.0 29.1 Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L et al. (2004) Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 292 (21):2585-90. DOI:10.1001/jama.292.21.2585 PMID: 15572716
  30. Prueksaritanont T, Tang C, Qiu Y, Mu L, Subramanian R, Lin JH (2002) Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos 30 (11):1280-7. PMID: 12386136
  31. Pan WJ, Gustavson LE, Achari R, Rieser MJ, Ye X, Gutterman C et al. (2000) Lack of a clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers. J Clin Pharmacol 40 (3):316-23. PMID: 10709162
  32. Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I et al. (2005) High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 294 (19):2437-45. DOI:10.1001/jama.294.19.2437 PMID: 16287954
  33. Wierzbicki AS (2003) Ezetimibe: a new addition to lipid-lowering therapy. Int J Clin Pract 57 (8):653-5. PMID: 14627172
  34. Schouten O, Hoeks SE, Welten GM, Davignon J, Kastelein JJ, Vidakovic R et al. (2007) Effect of statin withdrawal on frequency of cardiac events after vascular surgery. Am J Cardiol 100 (2):316-20. DOI:10.1016/j.amjcard.2007.02.093 PMID: 17631090
  35. Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC (2005) Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med 165 (7):725-30. DOI:10.1001/archinte.165.7.725 PMID: 15824290
  36. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR et al. (2005) Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366 (9500):1849-61. DOI:10.1016/S0140-6736(05)67667-2 PMID: 16310551
  37. Rensen PC, Jukema JW (2008) [Torcetrapib increases mortality in patients with a high risk of cardiovascular disorders.] Ned Tijdschr Geneeskd 152 (19):1088-90. PMID: 18552062
  38. 38.0 38.1 Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). Circulation 107 (1):149-58.[1] PMID: 12515758
  39. 39.0 39.1 Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina. Circulation 116 (23):2762-72.[2] PMID: 17998462
  40. 40.0 40.1 Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F; et al. (2006). "Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology". Eur Heart J. 27 (11): 1341–81. doi:10.1093/eurheartj/ehl001. PMID 16735367.

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