The renin-angiotensin-aldosterone system contributes to the progression of heart failure and its inhibition slows ventricular remodelling and favourably affects morbidity and mortality. -blockers exert a remarkably favourable effect on progression that may be mediated at least in part by renin inhibition. Although earlier trials suggested a possible adverse interaction when an angiotensin receptor blocker was added to an angiotensin-converting enzyme inhibitor and a -blocker, a recent study and newly analysed mechanistic data indicate that the triple combination provides modest additional inhibition of angiotensin that can further slow progression of disease.
CONSENSUS Trial Study Group: Effects of enalapril on mortality in severe congestive heart failure . N Engl J Med1987;316:1429-35.
2.
The SOLVD Investigators: Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med1991;325:293-302.
3.
The SOLVD Investigators: Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fraction. N Engl J Med1992;327:685-91.
4.
Packer M., Bristow MR, Cohn JN et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. US Carvedilol Heart Failure Study Group. N Engl J Med1996;334: 349-55.
5.
Cibis IIInvestigators and Committees. The Cardiac Insufficiency Bisoprolol Study (CIBIS-II): a randomised trial. Lancet1999;353:9-13.
6.
Merit-HF Study Group.Effect of metroprolol CR/XL in chronic heart failure: Metroprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet1999;353:2001-07.
7.
Packer M., Coats AJ, Fowler MB et al. Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect on carvedilol on survival in severe chronic heart failure. N Engl J Med2001;344:1651-8.
8.
Cohn JN, Tognoni G., Glazer RD, Spormann D., Hester A.Rationale and design of the Valsartan Heart Failure Trial: a large multinational trial to assess the effects of valsartan, an angiotensin-receptor blocker, on morbidity and mortality in chronic congestive heart failure. J Cardiac Fail1999;5:155-60.
9.
Pfeffer MA, Swedberg K., Granger CB et al., for the CHARM Investigators and Committees.Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet2003:362:759-66.
10.
Granger CB, McMurray JJV, Yusuf S. et al., for the CHARM Investigators and Committees.Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet2003:362:772-6.
11.
Packer M., Cohn JN, on behalf of the Steering Committee and Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure.Consensus recommendations for the management of chronic heart failure . Am J Cardiol1999;83(2A):1A-38A.
12.
Hunt SA, Baker DW, Chin MH et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation2001;104:2996-3007.
13.
McDonald KM , Mock J., D'Aloia A. et al. Bradykinin antagonism inhibits the antigrowth effect of converting enzyme inhibition in the dog myocardium after discrete transmural myocardial necrosis. Circulation1995;91:2043-8.
14.
Cohn JN, Pfeffer MA, Rouleau J. et al., for the MOXCON Investigators.Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail, in press.
15.
Campbell DJ , Aggarwal A., Esler M., Kaye D.β-blockers, angiotensin II, and ACE inhibitors in patients with heart failure. Lancet2001 ;358:1609-10.
16.
Pitt B., Poole-Wilson PA, Segal R. et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial - the Losartan Heart Failure Survival Study ELITE II. Lancet2000;355:1582-7.
17.
McMurray JJV , Östergren J., Swedberg K. et al., for the CHARM Investigators and Committees.Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet2003:362:767-71.1.
18.
Wong M., Staszewsky L., Latini R. et al. Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study. J Am Coll Cardiol2002;4:970-5.
19.
Anand IS, Fisher LD, Chiang YT et al. Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT) . Circulation2003;11:1278-83.
20.
Jorde, UP, Ennezat PV, Lisker J. et al. Maximally recommended doses of angiotensin converting enzyme (ACE) inhibitors do not completely prevent ACE-medicated formation of angiotensin II in chronic heart failure. Circulation2000 ; 101:844-6.
21.
Packer M., Poole-Wilson PA, Armstrong PW et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation1999 ;100:2312-18.
22.
Carson P., Krum H., Cohn JN, on behalf of the Val-HeFT Investigators.The effect of baseline ACE inhibitor dose on the efficacy of valsartan in Val-HeFT. (Abstract). Circulation2002:II-511.
23.
Pitt B., Zannad F., Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators . N Engl J Med1999;341:709-17.
24.
Pitt B., Remme W., Zannad F. et al. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction . N Engl J Med2003;348:1309-21.
