Chronic stable angina treatment newer antianginal agents: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
==Overview== | ==Overview== | ||
'''[[Ranolazine]]''' is a one of the newer FDA approved anti-anginal medication for management of chronic stable angina. '''[[Perhexiline]]''' is another anti-anginal, which has primarily been used in Australia and New Zealand and is being studied for use in the United States and UK. In patients with chronic stable angina, another effective agent with anti-anginal and anti-ischemic properties is '''[[ivabradine]]'''. | |||
==Mechanisms of benefit== | ==Mechanisms of benefit== | ||
| Line 11: | Line 9: | ||
*Persistent opening of these late sodium channel leads to intracellular sodium and calcium overload and subsequently increased diastolic stiffness, thereby leading to compression of the intramural vessels that supply the myocardium with blood and oxygen.<ref name="pmid18929234">Stone PH (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18929234 Ranolazine: new paradigm for management of myocardial ischemia, myocardial dysfunction, and arrhythmias.] ''Cardiol Clin'' 26 (4):603-14. [http://dx.doi.org/10.1016/j.ccl.2008.06.002 DOI:10.1016/j.ccl.2008.06.002] PMID: [http://pubmed.gov/18929234 18929234]</ref> Thus, inhibition of this effect results in improvement of [[ischemia]] and anginal symptoms. | *Persistent opening of these late sodium channel leads to intracellular sodium and calcium overload and subsequently increased diastolic stiffness, thereby leading to compression of the intramural vessels that supply the myocardium with blood and oxygen.<ref name="pmid18929234">Stone PH (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18929234 Ranolazine: new paradigm for management of myocardial ischemia, myocardial dysfunction, and arrhythmias.] ''Cardiol Clin'' 26 (4):603-14. [http://dx.doi.org/10.1016/j.ccl.2008.06.002 DOI:10.1016/j.ccl.2008.06.002] PMID: [http://pubmed.gov/18929234 18929234]</ref> Thus, inhibition of this effect results in improvement of [[ischemia]] and anginal symptoms. | ||
*[[Ivabradine]] selectively inhibits the pacemaker activity of the [[sinus node]] and hence is negatively chronotropic both at rest and during activity.<ref name="pmid12591750">Borer JS, Fox K, Jaillon P, Lerebours G, Ivabradine Investigators Group (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12591750 Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial.] ''Circulation'' 107 (6):817-23. PMID: [http://pubmed.gov/12591750 12591750]</ref><ref name="pmid16214830">Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K, INITIATIVE Investigators (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16214830 Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina.] ''Eur Heart J'' 26 (23):2529-36. [http://dx.doi.org/10.1093/eurheartj/ehi586 DOI:10.1093/eurheartj/ehi586] PMID: [http://pubmed.gov/16214830 16214830]</ref> | |||
==Indication== | ==Indication== | ||
Revision as of 15:42, 1 September 2011
|
Chronic stable angina Microchapters | ||
|
Classification | ||
|---|---|---|
| ||
| ||
|
Differentiating Chronic Stable Angina from Acute Coronary Syndromes | ||
|
Diagnosis | ||
|
Alternative Therapies for Refractory Angina | ||
|
Discharge Care | ||
|
Guidelines for Asymptomatic Patients | ||
|
Case Studies | ||
|
Chronic stable angina treatment newer antianginal agents On the Web | ||
|
FDA on Chronic stable angina treatment newer antianginal agents | ||
|
CDC onChronic stable angina treatment newer antianginal agents | ||
|
Chronic stable angina treatment newer antianginal agents in the news | ||
|
Blogs on Chronic stable angina treatment newer antianginal agents | ||
|
to Hospitals Treating Chronic stable angina treatment newer antianginal agents | ||
|
Risk calculators and risk factors for Chronic stable angina treatment newer antianginal agents | ||
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [6]; John Fani Srour, M.D.; Jinhui Wu, M.D.; Lakshmi Gopalakrishnan, M.B.B.S.
Overview
Ranolazine is a one of the newer FDA approved anti-anginal medication for management of chronic stable angina. Perhexiline is another anti-anginal, which has primarily been used in Australia and New Zealand and is being studied for use in the United States and UK. In patients with chronic stable angina, another effective agent with anti-anginal and anti-ischemic properties is ivabradine.
Mechanisms of benefit
- Ranolazine alters the trans-cellular late sodium current, which remains open in pathologic states such as ischemia and heart failure.[1]
- Persistent opening of these late sodium channel leads to intracellular sodium and calcium overload and subsequently increased diastolic stiffness, thereby leading to compression of the intramural vessels that supply the myocardium with blood and oxygen.[2] Thus, inhibition of this effect results in improvement of ischemia and anginal symptoms.
- Ivabradine selectively inhibits the pacemaker activity of the sinus node and hence is negatively chronotropic both at rest and during activity.[3][4]
Indication
- Ranolazine is effective as both monotherapy [5] and combination therapy [6] for the treatment and prevention of anginal episodes, however is not effective to relieve an episode of angina that has already begun.
- In patients, refractory to optimal medical therapy who are not candidates for revascularization, perhexiline may be indicated.[7][8]
Dosage
In asymptomatic patients, an initial dose of 500 mg twice daily may be required and a dose of 1000 mg twice daily may be required in symptomatic patients.
Adverse effects
- Ranolazine by inhibiting the HERG channel causes prolongation of QT interval.[9][10] Other mild side effects include nausea, constipation, headache, dizziness, palpitations.
- Side effects of perhexiline include hepatotoxicity and peripheral neuropathy.[11]
Supportive trial data
- In the MARISA trial, 191 patients with angina-limited exercise discontinued anti-anginal medications and were randomized to either ranolazine or placebo. The study reported patients with stable angina tolerated monotherapy better as evidenced by an increase in exercise performance and time to angina. However, the one-year survival did not decrease as expected (96.3 ± 1.7%).[5]
- In the CARISA trial, 823 patients with symptomatic chronic angina were randomized to either one of two doses of ranolazine or placebo. The study reported ranolazine offered additional anti-anginal and anti-ischemic efficacy as evidenced by increased exercise performance, time to angina and time to ST depression in patients with severe chronic angina who remain symptomatic while taking standard doses of atenolol, amlodipine, or diltiazem. There were no significant adverse long-term survival consequences over 1 to 2 years of therapy (One- and two-year survival rates of 98.4% and 95.9% respectively).[6]
- MERLIN TIMI 36 trial [12] and its sub study [13] are the most recent development in relation to ranolazine. In the MERLIN-TIMI 36 study, 6560 patients with prior chronic angina who received evidence based therapy (95% aspirin, 78% statins, 89% beta-blockers, average 2.9 antianginal agents) were randomized to either ranolazine or placebo. The primary end point of all cause mortality or non-fatal MI during a median follow-up of 1 year was less frequent with ranolazine (HR:0.86; 95% CI:0.75 to 0.97; p=0.017). The study concluded that ranolazine not only improved anti-ischemic effects in the 3565 patients with prior chronic stable angina (HR:0.77; 95% CI:0.59 to 1.00; p=0.048), but also showed anti-arrythmic effects with decrease incidence of ventricular tachycardia, SVT and ventricular pauses in ranolazine study group.
- In the ERICA trial,565 patients with stable coronary disease and more than three anginal attacks per week despite maximum recommended dosage of amlodipine (10 mg/day) and long acting nitrate therapy, were randomized to receive either ranolazine or placebo to assess the effect of ranolazine on the frequency of anginal episode per week. Enrolled patients had a baseline anginal frequency of 5.63 episodes per week, and nitroglycerin consumption of 4.72 tablets per week. The study reported significant reduction in the frequency of anginal episodes between the two groups: 2.88 in the ranolazine group and 3.31 in the placebo group (p=0.028). In addition, there was also significant reduction in the nitroglycerin consumption observed between the two groups: 20.3 in the ranolazine group and 2.68 in the placebo group (p=0.014).[14]
Vote on and Suggest Revisions to the Current Guidelines
Sources
- Guidelines on the management of stable angina pectoris: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology [15]
- The ACC/AHA/ACP–ASIM Guidelines for the Management of Patients With Chronic Stable Angina [16]
- TheACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina [17]
- The 2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina [18]
References
- ↑ Chaitman BR (2006) Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation 113 (20):2462-72. DOI:10.1161/CIRCULATIONAHA.105.597500 PMID: 16717165
- ↑ Stone PH (2008) Ranolazine: new paradigm for management of myocardial ischemia, myocardial dysfunction, and arrhythmias. Cardiol Clin 26 (4):603-14. DOI:10.1016/j.ccl.2008.06.002 PMID: 18929234
- ↑ Borer JS, Fox K, Jaillon P, Lerebours G, Ivabradine Investigators Group (2003) Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation 107 (6):817-23. PMID: 12591750
- ↑ Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K, INITIATIVE Investigators (2005) Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J 26 (23):2529-36. DOI:10.1093/eurheartj/ehi586 PMID: 16214830
- ↑ 5.0 5.1 Chaitman BR, Skettino SL, Parker JO, Hanley P, Meluzin J, Kuch J et al. (2004) Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol 43 (8):1375-82. DOI:10.1016/j.jacc.2003.11.045 PMID: 15093870
- ↑ 6.0 6.1 Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J et al. (2004) Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA 291 (3):309-16. DOI:10.1001/jama.291.3.309 PMID: 14734593
- ↑ White HD, Lowe JB (1983) Antianginal efficacy of perhexiline maleate in patients refractory to beta-adrenoreceptor blockade. Int J Cardiol 3 (2):145-55. PMID: 6134684
- ↑ Cole PL, Beamer AD, McGowan N, Cantillon CO, Benfell K, Kelly RA et al. (1990) Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent. Circulation 81 (4):1260-70. PMID: 2180591
- ↑ Schram G, Zhang L, Derakhchan K, Ehrlich JR, Belardinelli L, Nattel S (2004) Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects. Br J Pharmacol 142 (8):1300-8. DOI:10.1038/sj.bjp.0705879 PMID: 15277312
- ↑ Antzelevitch C, Belardinelli L, Wu L, Fraser H, Zygmunt AC, Burashnikov A et al. (2004) Electrophysiologic properties and antiarrhythmic actions of a novel antianginal agent. J Cardiovasc Pharmacol Ther 9 Suppl 1 ():S65-83. PMID: 15378132
- ↑ Lee L, Horowitz J, Frenneaux M (2004) Metabolic manipulation in ischaemic heart disease, a novel approach to treatment. Eur Heart J 25 (8):634-41. DOI:10.1016/j.ehj.2004.02.018 PMID: 15084367
- ↑ Scirica BM, Morrow DA, Hod H, Murphy SA, Belardinelli L, Hedgepeth CM et al. (2007) Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation 116 (15):1647-52. DOI:10.1161/CIRCULATIONAHA.107.724880 PMID: 17804441
- ↑ Wilson SR, Scirica BM, Braunwald E, Murphy SA, Karwatowska-Prokopczuk E, Buros JL et al. (2009) Efficacy of ranolazine in patients with chronic angina observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial. J Am Coll Cardiol 53 (17):1510-6. DOI:10.1016/j.jacc.2009.01.037 PMID: 19389561
- ↑ Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L, ERICA Investigators (2006) Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol 48 (3):566-75. DOI:10.1016/j.jacc.2006.05.044 PMID: 16875985
- ↑ Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F; et al. (2006). [url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367 [1] "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"] Check
|url=value (help). Eur Heart J. 27 (11): 1341–81. doi:10.1093/eurheartj/ehl001. PMID 16735367. - ↑ 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
- ↑ 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.[3] PMID: 12515758
- ↑ 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.[4] PMID: 17998462