2013


To access this material please log in or register

Register Authorize
2013/№6

Role of anti-ischemic drugs not affecting hemodynamics and / or heart rate in the treatment of patients with ischemic heart disease: Evidence-based rationales for the use

Gilyarevsky S. R., Golshmid M. V., Sinitsina I. I., Kuzmina I. I.

Keywords: CAD, ranolazine, trimetazidine, heart rate

DOI: 10.18087/rhj.2013.6.1872

The review presents evidence-based data demonstrating efficacy of trimetazidine and ranolazine, the drugs not affecting hemodynamics and / or heart rate, for treatment of patients with stable IHD. Despite the absence of strict proofs for a beneficial effect of such drugs on the prognosis, results of meta-analyses have suggested that the trimetazidine treatment is associated with a trend to reduced mortality of patients with CHF and decreased LV EF. Good tolerability and safety have been shown for both drugs.
  1. Stable angina: FULL guideline (July 2011). Available at: www.nice.org.uk.
  2. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF / AHA / ACP / AATS / PCNA / SCAI / STS guideline for the diagnosis and management of patients with stable ischemic heart disease: 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. 2012;126 (25):e354–471.
  3. Henderson RA, O'Flynn N; Guideline Development Group. Management of stable angina: summary of NICE guidance. Heart. 2012;98 (6):500–507.
  4. Sculpher MJ, Petticrew M, Kelland JL et al. Resource allocation for chronic stable angina: a systematic review of effectiveness, costs and cost-effectiveness of alternative interventions. Health Technol Assess. 1998;2 (10):i-iv, 1–176.
  5. Scottish Intercollegiate Guidelines Network. Management of Stable Angina. Edinburgh: NHS Quality Improvement Scotland, 2007.
  6. Fox K, Garcia MA, Ardissino D et al. 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. 2006;27 (11):1341–1381.
  7. Shu de F, Dong BR, Lin XF et al. Long-term beta blockers for stable angina: systematic review and meta-analysis. Eur J Prev Cardiol. 2012;19 (3):330–341.
  8. Daly C, Clemens F, Sendon J et al. The initial management of stable angina in Europe, from the Euro Heart Survey: a description of pharmacological management and revascularization strategies initiated within the first month of presentation to a cardiologist in the Euro Heart Survey of Stable Angina. Eur Heart J. 2005;26 (10):1011–1022.
  9. de Vries RJ, Dunselman PH, van Veldhuisen DJ et al. Comparison between felodipine and isosorbide mononitrate as adjunct to beta-blockade in patients >65 years of age with angina pectoris. Am J Cardiol. 1994;74 (12):1201–1206.
  10. Gori T, Parker JD. Nitrate-induced toxicity and preconditioning: a rationale for reconsidering the use of these drugs. J Am Coll Cardiol. 2008;52 (4):251–254.
  11. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH / ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31 (7):1281–1357.
  12. Messerli FH, Mancia G, Conti R et al. Dogma disputed: Can aggressively lowed blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med. 2006;144 (12):884–893.
  13. Sleight P, Redon J, Verdecchia P et al. Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study. J Hypertens. 2009;27 (7):1360–1369.
  14. Bangalore S, Messerli FH, Wun CC et al, Treating to New Targets Steering Committee and Investigators. J-Curve revisited: an analysis of the Treating to New Targets (TNT) Trial. J Am Coll Cardiol. 2009;53 (Suppl): A217.
  15. Bangalore S, Qin J, Sloan S et al. What is the optimal blood pressure in patients after acute coronary syndromes? Relationship of blood pressure and cardiovascular events in the PRavastatin OR atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial. Circulation. 2010;122 (21):2142–2151.
  16. Harpey C, Clauser P, Labrid C et al. Trimetazidine, a cellular anti-ischaemic agent. Cardiovascular Drugs Review. 1989;6:292–312.
  17. Lazar EJ, Frishman WH. Profile of an ideal antianginal agent. Drugs. 1989;38 (Suppl 2):1S-8S.
  18. Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3‑ketoacyl coenzyme A thiolase. Circ Res. 2000;86 (5):580–588.
  19. Barré J, Ledudal P, Oosterhuis B et al. Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure. Biopharm Drug Dispos. 2003;24 (4):159–164.
  20. Sellier P, Broustet JP. Assessment of anti-ischemic and antianginal effect at trough plasma concentration and safety of trimetazidine MR 35mg in patients with stable angina pectoris: A multicenter, doubleblind, placebo-controlled study. Am J Cardiovasc Drugs. 2003;3 (5):361–369.
  21. Szwed H, Sadowski Z, Elikowski W et al. Combination treatment in stable effort angina using trimetazidine and metoprolol: results of a randomized, double-blind, multicentre study (TRIMPOL II). TRIMetazidine in POLand. Eur Heart J. 2001;22 (24):2267–2274.
  22. Chazov EI, Lepakchin VK, Zharova EA et al. Trimetazidine in Angina Combination Therapy – the TACT study: trimetazidine versus conventional treatment in patients with stable angina pectoris in a randomized, placebo-controlled, multicenter study. Am J Ther. 2005;12 (1):35–42.
  23. Vitale C, Spoletini I, Malorni W et al. Efficacy of trimetazidine on functional capacity in symptomatic patients with stable exertional angina – The VASCO-angina study. Int J Cardiol. 2013;168 (2):1078–1081.
  24. Effect of 48‑h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy; A double-blind, placebo-controlled, randomized trial. The EMIP-FR Group. European Myocardial Infarction Project--Free Radicals. Eur Heart J. 2000;21 (18):1537–1546.
  25. Kim J, Han DC, Son CB et al. Effect of trimetazidine therapy in acute myocardial infarction patients. World congress of cardiology 2012. Dubai, United Arab Emirate, April 18–21, 2012. Abstract P195.
  26. Danchin N, Marzilli M, Parkhomenko A, Ribeiro JP. Efficacy comparison of trimetazidine with therapeutic alternatives in stable angina pectoris: a network meta-analysis. Cardiology. 2011;120 (2):59–72.
  27. Belardinelli R, Purcaro A. Effects of trimetazidine on the contractile response of chronically dysfunctional myocardium to low-dose dobutamine in ischaemic cardiomyopathy. Eur Heart J. 2001;22 (23):2164–2170.
  28. Tuunanen H, Engblom E, Naum A et al. Trimetazidine, a metabolic modulator, has cardiac and extracardiac benefits in idiopathic dila­ted cardiomyopathy. Circulation. 2008;118 (12):1250–1258.
  29. Packer M, Carver JR, Rodeheffer RJ et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med. 1991;325 (21):1468–1475.
  30. Cuffe MS, Califf RM, Adams KF Jr et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a rando­mized controlled trial. JAMA. 2002;287 (12):1541–1547.
  31. Gao D, Ning N, Niu X et al. Trimetazidine: a meta-analysis of randomised controlled trials in heart failure. Heart. 2011;97 (4):278–286.
  32. Zhang L, Lu Y, Jiang H et al. Additional use of trimetazidine in patients with chronic heart failure: a meta-analysis. J Am Coll Cardiol. 2012;59 (10):913–922.
  33. Haigney MC, Lakatta EG, Stern MD, Silverman HS. Sodium channel blockade reduces hypoxic sodium loading and sodium-dependent calcium loading. Circulation. 1994;90 (1):391–399.
  34. Chaitman BR, Pepine CJ, Parker JO et al. 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. 2004;291 (3):309–316.
  35. Stone PH, Gratsiansky NA, Blokhin A et al. Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006;48 (3):566–575.
  36. Mega JL, Hochman JS, Scirica BM et al. Clinical features and outcomes of women with unstable ischemic heart disease: observations from metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndromes-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36). Circulation. 2010;121 (16):1809–1817.
  37. Kosiborod M, Arnold SV, Spertus JA et al. Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: Results from the TERISA randomized clinical trial. J Am Coll Cardiol. 2013;61 (20):2038–2045.
Gilyarevsky S. R., Golshmid M. V., Sinitsina I. I. et al. Role of anti-ischemic drugs not affecting hemodynamics and / or heart rate in the treatment of patients with ischemic heart disease: Evidence-based rationales for the use. Russian Heart Journal. 2013;12(6):335-344

To access this material please log in or register

Register Authorize
Ru En