Chronic stable angina treatment calcium channel blockers: Difference between revisions
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{{Chronic stable angina}} | {{Chronic stable angina}} | ||
'''Editor-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com] | '''Editor-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com]; '''Associate Editor(s)-In-Chief:''' {{CZ}}; [[John Fani Srour, M.D.]]; [[WikiDoc Scholars#WikiDoc Scholars with Distinction|Jinhui Wu, M.D.]]; [[Lakshmi Gopalakrishnan|Lakshmi Gopalakrishnan, M.B.B.S.]];{{AA}} | ||
==Overview== | ==Overview== | ||
Calcium channel blockers (CCBs) consist of three sub-classes namely, dihydropyridines (e.g., [[nifedipine]]), phenylalkylamines (e.g., [[verapamil]]) and modified benzothiazepines (e.g., [[diltiazem]]). The beneficial | Calcium channel blockers (CCBs) consist of three sub-classes namely, dihydropyridines (e.g., [[nifedipine]]), phenylalkylamines (e.g., [[verapamil]]) and modified benzothiazepines (e.g., [[diltiazem]]). The beneficial anti-anginal effects of CCB include: reduction in the afterload consequent to systemic vasodilation as well as epicardial vessel vasodilation, enhancement of the coronary collateral flow with subsequent sub-endocardial perfusion due to the inhibition of calcium influx via L-type channels.<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> [[verapamil|Long-acting calcium channel blockers]] are an effective antianginal agent and are considered to be the first choice in post-MI patients with a contraindication to [[Chronic stable angina treatment beta blockers|beta-blocker]].<ref name="pmid1884725">Karlson BW, Emanuelsson H, Herlitz J, Nilsson JE, Olsson G (1991) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=1884725 Evaluation of the antianginal effect of nifedipine: influence of formulation dependent pharmacokinetics.] ''Eur J Clin Pharmacol'' 40 (5):501-6. PMID: [http://pubmed.gov/1884725 1884725]</ref> Long-acting CCBs are also specifically used to control symptoms in patients with [[Coronary Vasospasm|vasospastic angina]].<ref name="pmid1959210">Waters D (1991) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=1959210 Proischemic complications of dihydropyridine calcium channel blockers.] ''Circulation'' 84 (6):2598-600. PMID: [http://pubmed.gov/1959210 1959210]</ref> However [[dihydropyridines|short-acting CCBs]], such as [[nifedipine]], are avoided due to an increased risk of myocardial infarction and mortality.<ref name="pmid15536108">Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, Garza D et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15536108 Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial.] ''JAMA'' 292 (18):2217-25. [http://dx.doi.org/10.1001/jama.292.18.2217 DOI:10.1001/jama.292.18.2217] PMID: [http://pubmed.gov/15536108 15536108]</ref><ref name="pmid9652879">Savonitto S, Ardissino D (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9652879 Selection of drug therapy in stable angina pectoris.] ''Cardiovasc Drugs Ther'' 12 (2):197-210. PMID: [http://pubmed.gov/9652879 9652879]</ref><ref name="pmid10448616">Thadani U (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10448616 Treatment of stable angina.] ''Curr Opin Cardiol'' 14 (4):349-58. PMID: [http://pubmed.gov/10448616 10448616]</ref> | ||
==Mechanisms of | ==Calcium Channel Blockers== | ||
===Mechanisms of Benefit=== | |||
*Calcium channel blockers reduce the trans-membrane flux of calcium via inhibition of slow calcium channels. | *Calcium channel blockers reduce the trans-membrane flux of calcium via inhibition of slow calcium channels. | ||
*[[Dihydropyridines]] (e.g., [[nifedipine]]) exert a greater inhibitory effect on vascular smooth muscle than on the myocardium. Thus, major therapeutic effect are expected to be peripheral and coronary vasodilation. | *[[Dihydropyridines]] (e.g., [[nifedipine]]) exert a greater inhibitory effect on vascular smooth muscle than on the myocardium. Thus, major therapeutic effect are expected to be peripheral and coronary vasodilation. | ||
:* | :*Coronary vasodilation consequent to vasodilation of both, conductance and resistance coronary vessels as well as enhancement of the coronary collateral flow, subsequently results in sub-endocardial perfusion. | ||
:* | :*Peripheral vasodilation results in [[afterload|afterload reduction]] and subsequently sequences the reflex adrenergic activation, [[tachycardia]] and stimulation of the rennin-angiotensin system. This has been implicated as the mechanism for the potentially adverse cardiovascular effects. | ||
*[[Dihydropyridines]] also exert a | *[[Dihydropyridines]] also exert a negative inotropic effect and therefore can produce myocardial depression, which is less pronounced with [[amlodipine]] and [[nisoldipine]]. | ||
*Calcium channel blockers, such as [[verapamil]] and [[diltiazem]], may decrease heart rate and are associated with | *Calcium channel blockers, such as [[verapamil]] and [[diltiazem]], may decrease heart rate and are associated with reduced myocardial oxygen consumption. | ||
*Second generation vasoselective dihydropyridines, such as [[amlodipine]] and [[felodipine]], are well tolerated by patients with [[left ventricular dysfunction]] and result in no increase in the risk of mortality. Furthermore, vasoselective long acting dihydropyridines, such as [[amlodipine]], [[nifedipine|extended release nifedipine]], [[verapamil|slow release verapamil]] and [[diltiazem]], have all been shown to | *Second generation vasoselective dihydropyridines, such as [[amlodipine]] and [[felodipine]], are well tolerated by patients with [[left ventricular dysfunction]] and result in no increase in the risk of mortality. Furthermore, vasoselective long acting dihydropyridines, such as [[amlodipine]], [[nifedipine|extended release nifedipine]], [[verapamil|slow release verapamil]] and [[diltiazem]], have all been shown to reduce frequency and symptoms of angina. | ||
*Calcium channel blockers have also been postulated to have | *Calcium channel blockers have also been postulated to have anti atherosclerotic properties.<ref name="pmid12356398">Mancini GB, Pitt B (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12356398 Coronary angiographic changes in patients with cardiac events in the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT).] ''Am J Cardiol'' 90 (7):776-8. PMID: [http://pubmed.gov/12356398 12356398]</ref> | ||
==Indications== | ===Indications=== | ||
*In patients with a contra-indication to [[Chronic stable angina treatment beta blockers|beta blockers]], the second drug of choice is [[CCB|CCB]]. | *In patients with a contra-indication to [[Chronic stable angina treatment beta blockers|beta blockers]], the second drug of choice is [[CCB|CCB]]. | ||
*In patients with [[EF|ejection fraction more than 35%]], [[amlodipine]] can be combined with a [[Chronic stable angina treatment beta blockers|beta blocker]] as it offers minimal negative inotropic effects. | *In patients with [[EF|ejection fraction more than 35%]], [[amlodipine]] can be combined with a [[Chronic stable angina treatment beta blockers|beta blocker]] as it offers minimal negative inotropic effects. | ||
*In patients with stable exertional angina, calcium channel blockers primarily decrease the myocardial oxygen consumption and hence | *In patients with stable exertional angina, calcium channel blockers primarily decrease the myocardial oxygen consumption and hence improves exercise tolerance, reduces the time to onset of [[Chronic stable angina definition|angina]] and [[ST segment depression]] during treadmill tests. | ||
*In patients with [[Chronic stable angina clinical subset- vasospastic angina|vasospastic angina]], [[CCB|CCBs]] along with [[Chronic stable angina treatment nitrates|nitrates]] effectively relieve and prevent epicardial coronary artery spasm. Some patients may also require a combination of two calcium channel blockers to achieve efficacy. | *In patients with [[Chronic stable angina clinical subset- vasospastic angina|vasospastic angina]], [[CCB|CCBs]] along with [[Chronic stable angina treatment nitrates|nitrates]] effectively relieve and prevent epicardial coronary artery spasm. Some patients may also require a combination of two calcium channel blockers to achieve efficacy. | ||
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:*[[Diltiazem]] or [[verapamil]] is preferable in patients with relative [[tachycardia]]. | :*[[Diltiazem]] or [[verapamil]] is preferable in patients with relative [[tachycardia]]. | ||
== | ===Contraindications=== | ||
*A combination of [[Chronic stable angina treatment beta blockers|beta-blocker]] and [[diltiazem]] or [[dihydropyridine]] should be avoided in patients with [[EF|EF less than 40%]]. | *A combination of [[Chronic stable angina treatment beta blockers|beta-blocker]] and [[diltiazem]] or [[dihydropyridine]] should be avoided in patients with [[EF|EF less than 40%]]. | ||
*Concomitant use of [[verapamil]] with a [[Chronic stable angina treatment beta blockers|beta-blocker]] is considered unsafe as verapamil may cause conduction disturbances or worsen [[heart failure]]. | *Concomitant use of [[verapamil]] with a [[Chronic stable angina treatment beta blockers|beta-blocker]] is considered unsafe as verapamil may cause conduction disturbances or worsen [[heart failure]]. | ||
==Drug | ===Drug Interactions=== | ||
*[[Chronic stable angina treatment clopidogrel|Clopidogrel]] is activated by CYP3A4, which also metabolizes dihydropyridines, thus co-administration of [[dihydropyridines]] is associated with decreased platelet inhibition by clopidogrel.<ref name="pmid19007592">Siller-Matula JM, Lang I, Christ G, Jilma B (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19007592 Calcium-channel blockers reduce the antiplatelet effect of clopidogrel.] ''J Am Coll Cardiol'' 52 (19):1557-63. [http://dx.doi.org/10.1016/j.jacc.2008.07.055 DOI:10.1016/j.jacc.2008.07.055] PMID: [http://pubmed.gov/19007592 19007592]</ref> | *[[Chronic stable angina treatment clopidogrel|Clopidogrel]] is activated by CYP3A4, which also metabolizes dihydropyridines, thus co-administration of [[dihydropyridines]] is associated with decreased platelet inhibition by clopidogrel.<ref name="pmid19007592">Siller-Matula JM, Lang I, Christ G, Jilma B (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19007592 Calcium-channel blockers reduce the antiplatelet effect of clopidogrel.] ''J Am Coll Cardiol'' 52 (19):1557-63. [http://dx.doi.org/10.1016/j.jacc.2008.07.055 DOI:10.1016/j.jacc.2008.07.055] PMID: [http://pubmed.gov/19007592 19007592]</ref> | ||
*Concomitant use of [[Chronic stable angina treatment beta blockers|beta blockers]] and non-dihydropyridines such as [[verapamil]] and [[diltiazem]] cause the sinus node to slow down, thereby increasing the potential effect of [[bradycardia]]. | *Concomitant use of [[Chronic stable angina treatment beta blockers|beta blockers]] and non-dihydropyridines such as [[verapamil]] and [[diltiazem]] cause the sinus node to slow down, thereby increasing the potential effect of [[bradycardia]]. | ||
==Adverse | ===Adverse Effects=== | ||
*CCBs particularly [[dihydropyridines]]-induced peripheral vasodilation causes: | *CCBs particularly [[dihydropyridines]]-induced peripheral vasodilation causes: | ||
:*[[Peripheral edema]] | :*[[Peripheral edema]] | ||
:*[[Headache]] | :*[[Headache]] | ||
:*[[Flushing]] | :*[[Flushing]] | ||
:*[[Palpitation]] | :*[[Palpitation]] (due to reflex tachycardia) | ||
*[[Verapamil]] may cause [[constipation]]. | *[[Verapamil]] may cause [[constipation]]. | ||
*In [[MI|post-MI]] patients with reduced [[EF|left ventricular ejection fraction]], [[diltiazem]] causes worsening [[congestive heart failure]] and is associated with the increase risk of mortality.<ref name="pmid14615107">Turnbull F, Blood Pressure Lowering Treatment Trialists' Collaboration (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14615107 Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials.] ''Lancet'' 362 (9395):1527-35. PMID: [http://pubmed.gov/14615107 14615107]</ref> <ref name="pmid12777939">Staessen JA, Wang JG, Thijs L (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12777939 Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003.] ''J Hypertens'' 21 (6):1055-76. [http://dx.doi.org/10.1097/01.hjh.0000059044.65882.db DOI:10.1097/01.hjh.0000059044.65882.db] PMID: [http://pubmed.gov/12777939 12777939]</ref> <ref name="pmid12759325">Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12759325 Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis.] ''JAMA'' 289 (19):2534-44. [http://dx.doi.org/10.1001/jama.289.19.2534 DOI:10.1001/jama.289.19.2534] PMID: [http://pubmed.gov/12759325 12759325]</ref> | *In [[MI|post-MI]] patients with reduced [[EF|left ventricular ejection fraction]], [[diltiazem]] causes worsening [[congestive heart failure]] and is associated with the increase risk of mortality.<ref name="pmid14615107">Turnbull F, Blood Pressure Lowering Treatment Trialists' Collaboration (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14615107 Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials.] ''Lancet'' 362 (9395):1527-35. PMID: [http://pubmed.gov/14615107 14615107]</ref><ref name="pmid12777939">Staessen JA, Wang JG, Thijs L (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12777939 Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003.] ''J Hypertens'' 21 (6):1055-76. [http://dx.doi.org/10.1097/01.hjh.0000059044.65882.db DOI:10.1097/01.hjh.0000059044.65882.db] PMID: [http://pubmed.gov/12777939 12777939]</ref><ref name="pmid12759325">Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12759325 Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis.] ''JAMA'' 289 (19):2534-44. [http://dx.doi.org/10.1001/jama.289.19.2534 DOI:10.1001/jama.289.19.2534] PMID: [http://pubmed.gov/12759325 12759325]</ref> | ||
*[[Diltiazem]] and [[verapamil]] reduce myocardial contractility and therefore, can cause [[sinus bradycardia]] and different grades of | *[[Diltiazem]] and [[verapamil]] reduce myocardial contractility and therefore, can cause [[sinus bradycardia]] and different grades of atrioventricular blocks.<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> | ||
*Vaso-selective [[dihydropyridines]] such as [[nifedipine]], [[amlodipine]], and [[felodipine]] may elicit short term increase in [[heart rate]], sympathetic counterregulation and renin release that subside over time. However, there is persistence of sympathetic activation signs even after months of treatment with a dihydropyridines.<ref name="pmid9049538">Hjemdahl P, Wallén NH (1997) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9049538 Calcium antagonist treatment, sympathetic activity and platelet function.] ''Eur Heart J'' 18 Suppl A ():A36-50. PMID: [http://pubmed.gov/9049538 9049538]</ref> | *Vaso-selective [[dihydropyridines]] such as [[nifedipine]], [[amlodipine]], and [[felodipine]] may elicit short term increase in [[heart rate]], sympathetic counterregulation and renin release that subside over time. However, there is persistence of sympathetic activation signs even after months of treatment with a dihydropyridines.<ref name="pmid9049538">Hjemdahl P, Wallén NH (1997) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9049538 Calcium antagonist treatment, sympathetic activity and platelet function.] ''Eur Heart J'' 18 Suppl A ():A36-50. PMID: [http://pubmed.gov/9049538 9049538]</ref> | ||
==Supportive | ===Supportive Trial Data=== | ||
*A | *A meta-analysis on the safety of nifedipine in angina pectoris reviewed 60 randomized controlled trials to compare cardiovascular event rates in patients with stable angina receiving [[nifedipine]] as monotherapy or combination therapy and in active drug controls. Researchers reported that the primary endpoint from all major cardiovascular events such as death, non-fatal [[myocardial infarction]], [[stroke]] and revascularization procedure plus increased angina between the two groups was 1.61 (95% CI, 0.91 to 2.87). Researchers concluded that [[nifedipine]] was safe in the management of chronic stable angina.<ref name="pmid9931077">Stason WB, Schmid CH, Niedzwiecki D, Whiting GW, Caubet JF, Cory D et al. (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9931077 Safety of nifedipine in angina pectoris: a meta-analysis.] ''Hypertension'' 33 (1):24-31. PMID: [http://pubmed.gov/9931077 9931077]</ref> | ||
*A | *A meta-analysis reviewed 72 randomized trials to compare the efficacy of treatment with [[calcium channel blocker|calcium channel blockers]], [[Chronic stable angina treatment beta blockers|beta-blocker]] and [[Chronic stable angina treatment nitrates|long-acting nitrate]] therapy for patients with stable angina. The primary endpoint from all major cardiovascular events did not significantly differ between the beta-blocker and calcium channel blocker groups (OR 0.97; 95% CI, 0.67-1.38; P=0.79); however, differences between beta-blockers and calcium channel blockers were most striking with the [[Chronic stable angina treatment nitrates|nifedipine]] group (OR for adverse events with beta-blockers vs nifedipine 0.60; 95% CI, 0.47-0.77). Thus, the study concluded similar outcomes with both [[Chronic stable angina treatment beta blockers|beta-blocker]] and [[calcium channel blocker]] classes; the main limitation being only 8-weeks of follow-up suggesting further extended study would be needed to more definitively conclude this relationship.<ref name="pmid10362225">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=10362225 ACC/AHA/ACP-ASIM 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 (Committee on Management of Patients With Chronic Stable Angina).] ''J Am Coll Cardiol'' 33 (7):2092-197. PMID: [http://pubmed.gov/10362225 10362225]</ref> | ||
*In the | *In the ''CAPARES study'', a prospective double-blind trial of 405 patients who were randomized to receive either, [[amlodipine]] or placebo, prior to angioplasty exercise tests and 48-hour ambulatory ECG tests, assessed the effects of [[amlodipine]] on [[PTCA|post-PTCA ischemia]]. Researchers observed that amlodipine significantly reduced major cardiovascular end points such as death, [[MI]], [[CABG]], and repeat [[PCI]].<ref name="pmid12796759">Jørgensen B, Thaulow E, Coronary Angioplasty Amlodipine Restenosis Study (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12796759 Effects of amlodipine on ischemia after percutaneous transluminal coronary angioplasty: secondary results of the Coronary Angioplasty Amlodipine Restenosis (CAPARES) Study.] ''Am Heart J'' 145 (6):1030-5. [http://dx.doi.org/10.1016/S0002-8703(03)00082-6 DOI:10.1016/S0002-8703(03)00082-6] PMID: [http://pubmed.gov/12796759 12796759]</ref> | ||
*In the | *In the ''INTERCEPT'' trial, 874 patients with [[MI|acute MI]] were randomized to either [[diltiazem]] or placebo. During a 6-month follow-up, reduction in the primary end point of all cause of mortality, refractory ischemia and a significant reduction in the need for revascularization was observed in the group treated with [[diltiazem]].<ref name="pmid10832825">Boden WE, van Gilst WH, Scheldewaert RG, Starkey IR, Carlier MF, Julian DG et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10832825 Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis post-Thrombolysis (INTERCEPT)] ''Lancet'' 355 (9217):1751-6. PMID: [http://pubmed.gov/10832825 10832825]</ref> | ||
*In the | *In the ''ACTION'' trial, 7665 patients with stable angina were randomized to either [[nifedipine]] or placebo. The primary end point (0.97 [0.88-1.07], p=0.54) of all causes of mortality such as death, [[MI]], refractory angina, [[stroke|debilitating stroke]] and [[heart failure]] (0.89 [0.83-0.95], p=0.0012) during the 4.9 year follow-up did not significantly differ between the two groups. The study also reported that [[nifedipine]] therapy increased the need for peripheral revascularization (HR 1.25; P=0.073); however, the need for [[CABG|coronary bypass surgery]] was reduced in this group (HR 0.79; P=0.0021). Thus, the study concluded that [[nifedipine]] therapy had no effect on major cardiovascular event-free survival. Therefore, nifedipine therapy was concluded to be safe and reduced the need for coronary interventions.<ref name="pmid15351192">Poole-Wilson PA, Lubsen J, Kirwan BA, van Dalen FJ, Wagener G, Danchin N et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15351192 Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial.] ''Lancet'' 364 (9437):849-57. [http://dx.doi.org/10.1016/S0140-6736(04)16980-8 DOI:10.1016/S0140-6736(04)16980-8] PMID: [http://pubmed.gov/15351192 15351192]</ref> | ||
*In the | *In the ''CAMELOT study'', 1991 patients with angiographically documented [[coronary artery disease]] and diastolic blood pressure of more than 100 mm Hg were randomized to receive either [[amlodipine]], [[enalapril]], or placebo. During a 2-year follow-up, the study reported that [[amlodipine]] significantly reduced the primary end point (HR 0.81; 95% CI, 0.63-1.04; P=0.10) and cardiovascular event rate (HR 0.69; 95% CI, 0.54-0.88; P=0.003) in comparison to that of the [[enalapril]] group. The ''IVUS substudy'' showed evidence of slowing of atherosclerosis progression in [[amlodipine]].<ref name="pmid15536108">Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, Garza D et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15536108 Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial.] ''JAMA'' 292 (18):2217-25. [http://dx.doi.org/10.1001/jama.292.18.2217 DOI:10.1001/jama.292.18.2217] PMID: [http://pubmed.gov/15536108 15536108]</ref> | ||
*DAVIT trial and its sub study- MDPIT trail reported the benefits of [[verapamil]] and [[diltiazem]] in improving the prognosis of [[MI|post-MI]] patients. | *''DAVIT'' trial and its sub study- ''MDPIT'' trail reported the benefits of [[verapamil]] and [[diltiazem]] in improving the prognosis of [[MI|post-MI]] patients. | ||
:*In the | :*In the ''DAVIT'' trial, 897 [[MI|post-MI]] patients were randomized to either [[verapamil]] or placebo. The 18-month mortality rates were 11.1 and 13.8% (p=0.11) and the major event rates 18.0 and 21.6% (p=0.03) between the verapamil and placebo groups respectively. The study concluded that long-term therapy with [[verapamil]] in post-MI was beneficial as verapamil was associated with significant reduction in major events, and patients without [[heart failure]] reported a positive effect.<ref name="pmid2220572"> (1990) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=2220572 Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II--DAVIT II)] ''Am J Cardiol'' 66 (10):779-85. PMID: [http://pubmed.gov/2220572 2220572]</ref> | ||
:*In the | :*In the ''MDPIT study'', 2466 patients with previous infarction were randomized to either [[diltiazem]] or placebo. The primary endpoint of all cause mortality or non-fatal MI during a mean follow-up of 2 years (range 1 to 4.3 years) reported a 11% fewer recurrent cardiac events in the diltiazem group than in the placebo group (202 vs. 226; Cox hazard ratio, 0.90; 95 percent confidence limits, 0.74 and 1.08). Thus, the study concluded that [[diltiazem]] exerted no overall effect on mortality or cardiac events in patients with [[MI|previous infarction]].<ref name="pmid2899840"> (1988) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=2899840 The effect of diltiazem on mortality and reinfarction after myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group.] ''N Engl J Med'' 319 (7):385-92. [http://dx.doi.org/10.1056/NEJM198808183190701 DOI:10.1056/NEJM198808183190701] PMID: [http://pubmed.gov/2899840 2899840]</ref> | ||
== | ==2012 ACC/AHA/ACP–ASIM Guidelines for the Management of Patients With Chronic Stable Angina (DO NOT EDIT)<ref name="pmid23166210">{{cite journal| author=Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP et al.| title=2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. | journal=Circulation | year= 2012 | volume= 126 | issue= 25 | pages= 3097-137 | pmid=23166210 | doi=10.1161/CIR.0b013e3182776f83 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23166210 }} </ref>== | ||
===Calcium Channel Blockers (DO NOT EDIT)<ref name="pmid23166210">{{cite journal| author=Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP et al.| title=2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. | journal=Circulation | year= 2012 | volume= 126 | issue= 25 | pages= 3097-137 | pmid=23166210 | doi=10.1161/CIR.0b013e3182776f83 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23166210 }} </ref><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>=== | |||
{| class="wikitable" | {| class="wikitable" | ||
| Line 88: | Line 92: | ||
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]] | | colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]] | ||
|- | |- | ||
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' | | bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Calcium channel blockers or long-acting nitrates should be prescribed for relief of symptoms when beta blockers are contraindicated or cause unacceptable side effects in patients with SIHD. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki> | ||
|- | |- | ||
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' | | bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Calcium channel blockers or long-acting nitrates, in combination with beta blockers, should be prescribed for relief of symptoms when initial treatment with beta blockers is unsuccessful in patients with SIHD. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki> | ||
|} | |} | ||
| Line 99: | Line 101: | ||
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]] | | colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]] | ||
|- | |- | ||
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' | | bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Treatment with a long-acting nondihydropyridine calcium channel blocker (verapamil or diltiazem) instead of a beta blocker as initial therapy for relief of symptoms is reasonable in patients with SIHD ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki> | ||
|} | |} | ||
==ESC Guidelines- Pharmacological | ==ESC Guidelines- Pharmacological Therapy to Improve Symptoms and/or Reduce Ischaemia 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>== | ||
===Calcium Channel Blockers (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>=== | |||
{| class="wikitable" | {| class="wikitable" | ||
| Line 108: | Line 112: | ||
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]] | | colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]] | ||
|- | |- | ||
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In case of [[Chronic stable angina beta blocker therapy|beta-blocker intolerance]] or poor efficacy attempt monotherapy with a calcium channel blocker (CCB) ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'', [[Chronic stable angina nitrate therapy|long-acting nitrate]] ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'', or [[nicorandil]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]]) <nowiki>"</nowiki> | | bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In case of [[Chronic stable angina beta blocker therapy|beta-blocker intolerance]] or poor efficacy attempt monotherapy with a calcium channel blocker (CCB) ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'', [[Chronic stable angina nitrate therapy|long-acting nitrate]] ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'', or [[nicorandil]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])<nowiki>"</nowiki> | ||
|- | |- | ||
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' If the effects of [[Chronic stable angina beta blocker therapy|beta-blocker]] monotherapy are insufficient, add a [[CCB|dihydropyridine CCB]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki> | | bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' If the effects of [[Chronic stable angina beta blocker therapy|beta-blocker]] monotherapy are insufficient, add a [[CCB|dihydropyridine CCB]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki> | ||
|} | |} | ||
| Line 117: | Line 121: | ||
| colspan="1" style="text-align:center; background:LemonChiffon"| [[European society of cardiology#Classes of Recommendations|Class IIa]] | | colspan="1" style="text-align:center; background:LemonChiffon"| [[European society of cardiology#Classes of Recommendations|Class IIa]] | ||
|- | |- | ||
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' If [[CCB]] monotherapy or combination therapy (CCB with [[Chronic stable angina beta blocker therapy|beta-blocker]]) is unsuccessful, substitute the [[Chronic stable angina calcium channel blocker therapy|CCB]] with a [[Chronic stable angina nitrate therapy|long-acting nitrate]] or [[nicorandil]]. Be careful to avoid [[nitrate tolerance]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki> | | bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' If [[CCB]] monotherapy or combination therapy (CCB with [[Chronic stable angina beta blocker therapy|beta-blocker]]) is unsuccessful, substitute the [[Chronic stable angina calcium channel blocker therapy|CCB]] with a [[Chronic stable angina nitrate therapy|long-acting nitrate]] or [[nicorandil]]. Be careful to avoid [[nitrate tolerance]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki> | ||
|} | |} | ||
==References== | ==References== | ||
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Latest revision as of 18:27, 31 October 2016
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Chronic stable angina Microchapters | ||
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Classification | ||
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Differentiating Chronic Stable Angina from Acute Coronary Syndromes | ||
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Diagnosis | ||
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Alternative Therapies for Refractory Angina | ||
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Discharge Care | ||
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Guidelines for Asymptomatic Patients | ||
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Case Studies | ||
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Chronic stable angina treatment calcium channel blockers On the Web | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [4]; John Fani Srour, M.D.; Jinhui Wu, M.D.; Lakshmi Gopalakrishnan, M.B.B.S.;Aysha Anwar, M.B.B.S[5]
Overview
Calcium channel blockers (CCBs) consist of three sub-classes namely, dihydropyridines (e.g., nifedipine), phenylalkylamines (e.g., verapamil) and modified benzothiazepines (e.g., diltiazem). The beneficial anti-anginal effects of CCB include: reduction in the afterload consequent to systemic vasodilation as well as epicardial vessel vasodilation, enhancement of the coronary collateral flow with subsequent sub-endocardial perfusion due to the inhibition of calcium influx via L-type channels.[1] Long-acting calcium channel blockers are an effective antianginal agent and are considered to be the first choice in post-MI patients with a contraindication to beta-blocker.[2] Long-acting CCBs are also specifically used to control symptoms in patients with vasospastic angina.[3] However short-acting CCBs, such as nifedipine, are avoided due to an increased risk of myocardial infarction and mortality.[4][5][6]
Calcium Channel Blockers
Mechanisms of Benefit
- Calcium channel blockers reduce the trans-membrane flux of calcium via inhibition of slow calcium channels.
- Dihydropyridines (e.g., nifedipine) exert a greater inhibitory effect on vascular smooth muscle than on the myocardium. Thus, major therapeutic effect are expected to be peripheral and coronary vasodilation.
- Coronary vasodilation consequent to vasodilation of both, conductance and resistance coronary vessels as well as enhancement of the coronary collateral flow, subsequently results in sub-endocardial perfusion.
- Peripheral vasodilation results in afterload reduction and subsequently sequences the reflex adrenergic activation, tachycardia and stimulation of the rennin-angiotensin system. This has been implicated as the mechanism for the potentially adverse cardiovascular effects.
- Dihydropyridines also exert a negative inotropic effect and therefore can produce myocardial depression, which is less pronounced with amlodipine and nisoldipine.
- Calcium channel blockers, such as verapamil and diltiazem, may decrease heart rate and are associated with reduced myocardial oxygen consumption.
- Second generation vasoselective dihydropyridines, such as amlodipine and felodipine, are well tolerated by patients with left ventricular dysfunction and result in no increase in the risk of mortality. Furthermore, vasoselective long acting dihydropyridines, such as amlodipine, extended release nifedipine, slow release verapamil and diltiazem, have all been shown to reduce frequency and symptoms of angina.
- Calcium channel blockers have also been postulated to have anti atherosclerotic properties.[7]
Indications
- In patients with a contra-indication to beta blockers, the second drug of choice is CCB.
- In patients with ejection fraction more than 35%, amlodipine can be combined with a beta blocker as it offers minimal negative inotropic effects.
- In patients with stable exertional angina, calcium channel blockers primarily decrease the myocardial oxygen consumption and hence improves exercise tolerance, reduces the time to onset of angina and ST segment depression during treadmill tests.
- In patients with vasospastic angina, CCBs along with nitrates effectively relieve and prevent epicardial coronary artery spasm. Some patients may also require a combination of two calcium channel blockers to achieve efficacy.
- In patients with mixed angina, walk through, postprandial, and late nocturnal angina, an increase in the coronary vascular tone appears to be the contributing factor for the pathogenesis of ischemia. The above mentioned types of angina benefit with the use of calcium channel blockers, particularly when nitrate therapy alone is inadequate.
- The new T-channel types of calcium blockers possess minimal negative inotropic effects, produce no edema or constipation and are effective in the management of hypertension and chronic angina.
- In a given patient, the hemodynamic profile should be considered while choosing a particular calcium channel blocker.
- Dihydropyridines are preferable in the presence of sinus bradycardia, sinus node dysfunction, or atrioventricular block, particularly when the blood pressure is not adequately controlled.
- Diltiazem or verapamil is preferable in patients with relative tachycardia.
Contraindications
- A combination of beta-blocker and diltiazem or dihydropyridine should be avoided in patients with EF less than 40%.
- Concomitant use of verapamil with a beta-blocker is considered unsafe as verapamil may cause conduction disturbances or worsen heart failure.
Drug Interactions
- Clopidogrel is activated by CYP3A4, which also metabolizes dihydropyridines, thus co-administration of dihydropyridines is associated with decreased platelet inhibition by clopidogrel.[8]
- Concomitant use of beta blockers and non-dihydropyridines such as verapamil and diltiazem cause the sinus node to slow down, thereby increasing the potential effect of bradycardia.
Adverse Effects
- CCBs particularly dihydropyridines-induced peripheral vasodilation causes:
- Peripheral edema
- Headache
- Flushing
- Palpitation (due to reflex tachycardia)
- Verapamil may cause constipation.
- In post-MI patients with reduced left ventricular ejection fraction, diltiazem causes worsening congestive heart failure and is associated with the increase risk of mortality.[9][10][11]
- Diltiazem and verapamil reduce myocardial contractility and therefore, can cause sinus bradycardia and different grades of atrioventricular blocks.[12]
- Vaso-selective dihydropyridines such as nifedipine, amlodipine, and felodipine may elicit short term increase in heart rate, sympathetic counterregulation and renin release that subside over time. However, there is persistence of sympathetic activation signs even after months of treatment with a dihydropyridines.[13]
Supportive Trial Data
- A meta-analysis on the safety of nifedipine in angina pectoris reviewed 60 randomized controlled trials to compare cardiovascular event rates in patients with stable angina receiving nifedipine as monotherapy or combination therapy and in active drug controls. Researchers reported that the primary endpoint from all major cardiovascular events such as death, non-fatal myocardial infarction, stroke and revascularization procedure plus increased angina between the two groups was 1.61 (95% CI, 0.91 to 2.87). Researchers concluded that nifedipine was safe in the management of chronic stable angina.[14]
- A meta-analysis reviewed 72 randomized trials to compare the efficacy of treatment with calcium channel blockers, beta-blocker and long-acting nitrate therapy for patients with stable angina. The primary endpoint from all major cardiovascular events did not significantly differ between the beta-blocker and calcium channel blocker groups (OR 0.97; 95% CI, 0.67-1.38; P=0.79); however, differences between beta-blockers and calcium channel blockers were most striking with the nifedipine group (OR for adverse events with beta-blockers vs nifedipine 0.60; 95% CI, 0.47-0.77). Thus, the study concluded similar outcomes with both beta-blocker and calcium channel blocker classes; the main limitation being only 8-weeks of follow-up suggesting further extended study would be needed to more definitively conclude this relationship.[15]
- In the CAPARES study, a prospective double-blind trial of 405 patients who were randomized to receive either, amlodipine or placebo, prior to angioplasty exercise tests and 48-hour ambulatory ECG tests, assessed the effects of amlodipine on post-PTCA ischemia. Researchers observed that amlodipine significantly reduced major cardiovascular end points such as death, MI, CABG, and repeat PCI.[16]
- In the INTERCEPT trial, 874 patients with acute MI were randomized to either diltiazem or placebo. During a 6-month follow-up, reduction in the primary end point of all cause of mortality, refractory ischemia and a significant reduction in the need for revascularization was observed in the group treated with diltiazem.[17]
- In the ACTION trial, 7665 patients with stable angina were randomized to either nifedipine or placebo. The primary end point (0.97 [0.88-1.07], p=0.54) of all causes of mortality such as death, MI, refractory angina, debilitating stroke and heart failure (0.89 [0.83-0.95], p=0.0012) during the 4.9 year follow-up did not significantly differ between the two groups. The study also reported that nifedipine therapy increased the need for peripheral revascularization (HR 1.25; P=0.073); however, the need for coronary bypass surgery was reduced in this group (HR 0.79; P=0.0021). Thus, the study concluded that nifedipine therapy had no effect on major cardiovascular event-free survival. Therefore, nifedipine therapy was concluded to be safe and reduced the need for coronary interventions.[18]
- In the CAMELOT study, 1991 patients with angiographically documented coronary artery disease and diastolic blood pressure of more than 100 mm Hg were randomized to receive either amlodipine, enalapril, or placebo. During a 2-year follow-up, the study reported that amlodipine significantly reduced the primary end point (HR 0.81; 95% CI, 0.63-1.04; P=0.10) and cardiovascular event rate (HR 0.69; 95% CI, 0.54-0.88; P=0.003) in comparison to that of the enalapril group. The IVUS substudy showed evidence of slowing of atherosclerosis progression in amlodipine.[4]
- DAVIT trial and its sub study- MDPIT trail reported the benefits of verapamil and diltiazem in improving the prognosis of post-MI patients.
- In the DAVIT trial, 897 post-MI patients were randomized to either verapamil or placebo. The 18-month mortality rates were 11.1 and 13.8% (p=0.11) and the major event rates 18.0 and 21.6% (p=0.03) between the verapamil and placebo groups respectively. The study concluded that long-term therapy with verapamil in post-MI was beneficial as verapamil was associated with significant reduction in major events, and patients without heart failure reported a positive effect.[19]
- In the MDPIT study, 2466 patients with previous infarction were randomized to either diltiazem or placebo. The primary endpoint of all cause mortality or non-fatal MI during a mean follow-up of 2 years (range 1 to 4.3 years) reported a 11% fewer recurrent cardiac events in the diltiazem group than in the placebo group (202 vs. 226; Cox hazard ratio, 0.90; 95 percent confidence limits, 0.74 and 1.08). Thus, the study concluded that diltiazem exerted no overall effect on mortality or cardiac events in patients with previous infarction.[20]
2012 ACC/AHA/ACP–ASIM Guidelines for the Management of Patients With Chronic Stable Angina (DO NOT EDIT)[21]
Calcium Channel Blockers (DO NOT EDIT)[21][12]
| Class I |
| "1. Calcium channel blockers or long-acting nitrates should be prescribed for relief of symptoms when beta blockers are contraindicated or cause unacceptable side effects in patients with SIHD. (Level of Evidence: B)" |
| "2. Calcium channel blockers or long-acting nitrates, in combination with beta blockers, should be prescribed for relief of symptoms when initial treatment with beta blockers is unsuccessful in patients with SIHD. (Level of Evidence: B)" |
| Class IIa |
| "1. Treatment with a long-acting nondihydropyridine calcium channel blocker (verapamil or diltiazem) instead of a beta blocker as initial therapy for relief of symptoms is reasonable in patients with SIHD (Level of Evidence: B)" |
ESC Guidelines- Pharmacological Therapy to Improve Symptoms and/or Reduce Ischaemia in Patients with Stable Angina (DO NOT EDIT)[22]
Calcium Channel Blockers (DO NOT EDIT)[22]
| Class I |
| "1. In case of beta-blocker intolerance or poor efficacy attempt monotherapy with a calcium channel blocker (CCB) (Level of Evidence: A), long-acting nitrate (Level of Evidence: C), or nicorandil. (Level of Evidence: C)" |
| "2. If the effects of beta-blocker monotherapy are insufficient, add a dihydropyridine CCB. (Level of Evidence: B)" |
| Class IIa |
| "1. If CCB monotherapy or combination therapy (CCB with beta-blocker) is unsuccessful, substitute the CCB with a long-acting nitrate or nicorandil. Be careful to avoid nitrate tolerance. (Level of Evidence: C)" |
References
- ↑ 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
- ↑ Karlson BW, Emanuelsson H, Herlitz J, Nilsson JE, Olsson G (1991) Evaluation of the antianginal effect of nifedipine: influence of formulation dependent pharmacokinetics. Eur J Clin Pharmacol 40 (5):501-6. PMID: 1884725
- ↑ Waters D (1991) Proischemic complications of dihydropyridine calcium channel blockers. Circulation 84 (6):2598-600. PMID: 1959210
- ↑ 4.0 4.1 Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, Garza D et al. (2004) Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA 292 (18):2217-25. DOI:10.1001/jama.292.18.2217 PMID: 15536108
- ↑ Savonitto S, Ardissino D (1998) Selection of drug therapy in stable angina pectoris. Cardiovasc Drugs Ther 12 (2):197-210. PMID: 9652879
- ↑ Thadani U (1999) Treatment of stable angina. Curr Opin Cardiol 14 (4):349-58. PMID: 10448616
- ↑ Mancini GB, Pitt B (2002) Coronary angiographic changes in patients with cardiac events in the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT). Am J Cardiol 90 (7):776-8. PMID: 12356398
- ↑ Siller-Matula JM, Lang I, Christ G, Jilma B (2008) Calcium-channel blockers reduce the antiplatelet effect of clopidogrel. J Am Coll Cardiol 52 (19):1557-63. DOI:10.1016/j.jacc.2008.07.055 PMID: 19007592
- ↑ Turnbull F, Blood Pressure Lowering Treatment Trialists' Collaboration (2003) Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 362 (9395):1527-35. PMID: 14615107
- ↑ Staessen JA, Wang JG, Thijs L (2003) Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003. J Hypertens 21 (6):1055-76. DOI:10.1097/01.hjh.0000059044.65882.db PMID: 12777939
- ↑ Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH et al. (2003) Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA 289 (19):2534-44. DOI:10.1001/jama.289.19.2534 PMID: 12759325
- ↑ 12.0 12.1 Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM et al. (1999) 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. [2] PMID: 10351980
- ↑ Hjemdahl P, Wallén NH (1997) Calcium antagonist treatment, sympathetic activity and platelet function. Eur Heart J 18 Suppl A ():A36-50. PMID: 9049538
- ↑ Stason WB, Schmid CH, Niedzwiecki D, Whiting GW, Caubet JF, Cory D et al. (1999) Safety of nifedipine in angina pectoris: a meta-analysis. Hypertension 33 (1):24-31. PMID: 9931077
- ↑ Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM et al. (1999) ACC/AHA/ACP-ASIM 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 (Committee on Management of Patients With Chronic Stable Angina). J Am Coll Cardiol 33 (7):2092-197. PMID: 10362225
- ↑ Jørgensen B, Thaulow E, Coronary Angioplasty Amlodipine Restenosis Study (2003) Effects of amlodipine on ischemia after percutaneous transluminal coronary angioplasty: secondary results of the Coronary Angioplasty Amlodipine Restenosis (CAPARES) Study. Am Heart J 145 (6):1030-5. DOI:10.1016/S0002-8703(03)00082-6 PMID: 12796759
- ↑ Boden WE, van Gilst WH, Scheldewaert RG, Starkey IR, Carlier MF, Julian DG et al. (2000) Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis post-Thrombolysis (INTERCEPT) Lancet 355 (9217):1751-6. PMID: 10832825
- ↑ Poole-Wilson PA, Lubsen J, Kirwan BA, van Dalen FJ, Wagener G, Danchin N et al. (2004) Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial. Lancet 364 (9437):849-57. DOI:10.1016/S0140-6736(04)16980-8 PMID: 15351192
- ↑ (1990) Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II--DAVIT II) Am J Cardiol 66 (10):779-85. PMID: 2220572
- ↑ (1988) The effect of diltiazem on mortality and reinfarction after myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group. N Engl J Med 319 (7):385-92. DOI:10.1056/NEJM198808183190701 PMID: 2899840
- ↑ 21.0 21.1 Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP; et al. (2012). "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". Circulation. 126 (25): 3097–137. doi:10.1161/CIR.0b013e3182776f83. PMID 23166210.
- ↑ 22.0 22.1 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.