Chronic stable angina treatment newer antianginal agents
|
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 the use for chronic angina.
- Another anti-anginal which has primarily been used in Australia and New Zealand is Perhexiline is being studied for use in United States and UK.
Mechanisms of benefit
- Ranolazine alters the trans-cellular late sodium current, which remains open in pathologic states such as ischemia and heart failure.
- 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. Thus, inhibition of this effect results in improvement of ischemia and anginal symptoms.
Indication
Ranolazine is effective as both monotherapy [1] and combination therapy [2] for the treatment and prevention of anginal episodes, however is not effective to relieve an episode of angina that has already begun.
Adverse effects
- Mild side effects include nausea, constipation, headache, dizziness.
- Severe side effects include palpitations, prolong QT syndrome.
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 increased exercise performance and monotherapy being well tolerated in patients with chronic stable angina. However, one-year survival was not lower than expected (96.3 ± 1.7%).[1]
- In the CARISA trial, 823 patients with symptomatic chronic angina were randomized to either 1 of 2 doses of ranolazine or placebo. The study reported ranolazine offered additional anti-anginal and anti-ischemic efficacy 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).[2]
- MERLIN TIMI 36 trial [3] and its sub study [4] 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.
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 [5]
- The ACC/AHA/ACP–ASIM Guidelines for the Management of Patients With Chronic Stable Angina [6]
- TheACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina [7]
- The 2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina [8]
References
- ↑ 1.0 1.1 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
- ↑ 2.0 2.1 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
- ↑ 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
- ↑ 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