• angiotensin coverting enzyme inhibitor
• angiotensin II receptor blocker
• heart failure

• ACE-I, angiotensin converting enzyme inhibitor
• ARB, angiotensin II receptor blocker
• CHARM, candesarton in heart failure—assessment of reduction in mortality and morbidity
• ELITE, evaluation of losartan in the elderly
• NYHA, New York Heart Association
• OPTIMAAL, optimal trial in myocardial infarction with the angiotensin II antagonist losartan
• RENAAL, reduction of end points in NIDDM with the angiotensin II antagonist losartan
• VALIANT, valsartan in acute myocardial infarction trial
• Val-HeFT, valsartan heart failure trial

Chronic heart failure is one of the most serious cardiac problems encountered in clinical practice. Modulation of the renin angiotensin system is a key element in the treatment of this syndrome. There is overwhelming evidence in favour of the benefit of angiotensin converting enzyme (ACE) inhibitors on morbidity and mortality in mild to severe heart failure and in heart failure or left ventricular dysfunction following acute myocardial infarction.¹ It is not known, however, whether the benefit of ACE inhibition is solely attributable to blockade of angiotensin II production or also related to bradykinin accumulation.² Moreover, bradykinin accumulation has been implicated in the adverse effects observed with ACE inhibitors such a cough and might result in prejunctional noradrenaline (norepinephrine) release.³

The development of orally active, non-peptide angiotensin II type I receptor blockers (ARBs) has raised hopes for a new generation of modulators of the renin angiotensin system better tolerated and potentially more powerful. Since ARBs block directly the binding of angiotensin II to the receptor which mediates harmful biological actions such as vasoconstriction, aldosterone synthesis, and trophic effects, one potential advantage is to avoid the ACE independent pathway generation of angiotensin II.

Have these theoretical advantages become reality for the treatment of chronic heart failure?

The excitement in designing a large trial comparing an ARB to an ACE inhibitor in chronic heart failure is mainly based on the results of the ELITE I trial.⁴ In this study, which enrolled 722 elderly patients and compared losartan 50 mg/day to captopril 150 mg/day, it was shown that a secondary end point favoured losartan with a risk reduction of death/hospital admission for heart failure of 32%, primarily due to a decrease …