β-blockade with nebivolol for prevention of acute ischaemic events in elderly patients with heart failure
https://doi.org/10.15829/1728-8800-2011-4-69-76
Abstract
Aim. This subanalysis of the Study of the Effects of Nebivolol Intervention on Outcomes and Hospitalisation in Seniors with Heart Failure (SENIORS) investigates whether treatment with nebivolol, a β-blocker with nitric oxide-releasing properties, can provide additional benefits besides its effects on heart failure (HF), by reducing cardiac ischaemic events in patients with HF of ischaemic aetiology.
Material and methods. A double-blind, randomised, placebo-controlled, multicentre trial of nebivolol in 2128 elderly patients. For this analysis, data were extracted for 2128 elderly (≥70 years) HF patients in whom coronary artery disease (CAD) was the underlying aetiology (68,2 %; 717 placebo-treated patients and 735 assigned to nebivolol). The main endpoint was the composite of cardiac ischaemic events at 2 year follow-up: death/hospitalisation for myocardial infarction, unstable angina or sudden death, as originally identified in the case report form.
Results. At follow-up, nebivolol treatment was associated with a one-third reduction in the risk of ischaemic events, the composite endpoint occurring in 15,9 % of placebo and 10,7 % of nebivolol-treated patients (HR 0,68; 95 % CI 0,51 to 0,90; p=0,008). This effect was independent of age, gender and ejection fraction. No difference in this composite endpoint was observed in the subgroup of patients of non-ischaemic aetiology.
Conclusion. Nebivolol was effective in reducing cardiac ischaemic events in patients with HF of ischaemic aetiology. The prevention of ischaemic events can be an additional beneficial effect of β-blockade in HF patients with underlying CAD.
About the Authors
G. AmbrosioItaly
Perugia
M. D. Flather
United Kingdom
London
M. Böhm
Germany
Homburg/Saar
A. J.S. Coats
Australia
L. Tavazzi
Italy
Pavia
D. J. van Veldhuisen
Netherlands
Groningen
M. G. Conti
Italy
Perugia
G. Spinucci
Italy
Perugia
F. Mascagni
Italy
Pozzo della Chiana
A. Murrone
Italy
Perugia
A. Cohen-Solal
France
Paris
References
1. Jessup M, Brozena S. Heart failure. N Engl J Med 2003;348:2007-18.
2. Bo¨hm M, Maack C. Treatment of heart failure with beta-blockers. Mechanisms and results. Basic Res Cardiol 2000;95(Suppl 1):I15-24.
3. Lechat P, Packer M, Chalon S, et al. Clinical effects of betaadrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation 1998;98:1184-91.
4. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001-7.
5. CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9-13.
6. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651-8.
7. Poole-Wilson PA, Swedberg K, Cleland JG, et al; Carvedilol or Metoprolol European Trial Investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 2003;362:7-13.
8. O’Connor CM, Gottlieb S, Bourque JM, et al; on behalf of the BEST Investigators. Impact of nonfatal myocardial infarction on outcomes in patients with advanced heart failure and the effect of bucindolol therapy. Am J Cardiol 2005;95:558-64.
9. Fraker TD Jr, Fihn SD, Gibbons RJ, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group. 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 2007;116:2762-72.
10. Norwegian Multicentre Group. Timolol induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 1981;304:801-7.
11. b-Blocker Heart Attack Trial Research Group. A randomised trial of propranolol in patients with acute myocardial infarction. I: Mortality and result. JAMA 1982;247:1707-14.
12. Yusuf S, Peto R, Lewis J, et al. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 1985;27:335-71.
13. Lo´pez-Sendo´n J, Swedberg K, McMurray J, et al; Task Force on Beta-blockers of the European Society of Cardiology. Expert consensus document on beta-adrenergic receptor blockers. Eur Heart J 2004;15:1341-62.
14. Gheorghiade M, Sopko G, De Luca L, et al. Navigating the crossroads of coronary artery disease and heart failure. Circulation 2006;114:1202-13.
15. Mu¨nzel T, Gori T. Nebivolol: the somewhat-different betaadrenergic receptor blocker. J Am Coll Cardiol 2009;54:1491-9.
16. Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005;26:215-25.
17. van Veldhuisen DJ, Cohen-Solal A, Bo¨hm M, et al. Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: data from SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure). J Am Coll Cardiol 2009;53:2150-8.
18. Tritto I, Ambrosio G. The multi-faceted behavior of nitric oxide in vascular “inflammation”: catchy terminology or true phenomenon? Cardiovasc Res 2004;63:1-4.
19. Dargie H, Colucci WS, Ford I, et al. Effect of carvedilol on outcome after myocardial infarction in patients with leftventricular dysfunction: the CAPRICORN randomised trial. Lancet 2001;357:1385-90.
20. Australia/New Zealand Heart Failure Research Collaborative Group. Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Lancet 1997;349:375-80.
21. Remme WJ, Torp-Pedersen C, Cleland JG, et al. Carvedilol protects better against vascular events than metoprolol in heart failure: results from COMET. J Am Coll Cardiol 2007;49:963-71.
22. Colucci WS, Packer M, Bristow MR, et al. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. US Carvedilol Heart Failure Study Group. Circulation 1996;94:2800-6.
23. Ja´nosi A, Ghali JK, Herlitz J, et al; MERITeHF Study Group. Metoprolol CR/XL in postmyocardial infarction patients with chronic heart failure: experiences from MERITeHF. Am Heart J 2003;146:721-8.
24. Packer M, Fowler MB, Roecker EB, et al; Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study Group. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation 2002;106:2194-9.
25. The Beta-blocker Evaluation of Survival Trial Investigators. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001;344:1659-67.
26. Mehta D, Curwin J, Gomes JA, et al. Sudden death in coronary artery disease: acute ischemia versus myocardial substrate. Circulation 1997;96:3215-23.
27. Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhythmias. N Engl J Med 2001;20:1473-82.
28. Ali Raza J, Movahed A. Use of cardiovascular medications in the elderly. Int J Cardiol 2002;85:203-15.
29. Zanchetti A. Clinical pharmacodynamics of nebivolol: new evidence of nitric oxidemediated vasodilating activity and peculiar haemodynamic properties in hypertensive patients. Blood Press Suppl 2004;1:17-32.
30. Maffei A, Di Pardo A, Carangi R, et al. Nebivolol induces nitric oxide release in the heart through inducible nitric oxide synthase activation. Hypertension 2007;50:652-6.
31. Cominacini L, Pasini AF, Garbin U, et al. Nebivolol and its 4-keto derivative increase nitric oxide in endothelial cells by reducing its oxidative inactivation. JACC 2003;42:1838-44.
32. Bolli R. Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research. J Mol Cell Cardiol 2001;33:1897-918.
33. Yellon DM, Downey JM. Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 2003;83:1113-51.
34. Cohen MV, Yang XM, Downey JM. Nitric oxide is a preconditioning mimetic and cardioprotectant and is the basis of many available infarct-sparing strategies. Cardiovasc Res 2006;70:231-9.
35. Leesar MA, Stoddard MF, Dawn B, et al. Delayed preconditioningmimetic action of nitroglycerin in patients undergoing coronary angioplasty. Circulation 2001;103:2935-41.
36. Ambrosio G, del Pinto M, Tritto I, et al; for the GRACE investigators. Chronic nitrate therapy is associated with different presentation and evolution of acute coronary syndromes: insights from 52,693 patients in the Global Registry of Acute Coronary Events (GRACE). Eur Heart J 2010;31:430-8.
Review
For citations:
Ambrosio G., Flather M.D., Böhm M., Coats A.J., Tavazzi L., van Veldhuisen D.J., Conti M.G., Spinucci G., Mascagni F., Murrone A., Cohen-Solal A. β-blockade with nebivolol for prevention of acute ischaemic events in elderly patients with heart failure. Cardiovascular Therapy and Prevention. 2011;10(4):69-76. (In Russ.) https://doi.org/10.15829/1728-8800-2011-4-69-76