Volume 2, Number 2, June 2001

Angiotensin II receptor antagonists for the treatment of heart failure: what is their place after ELITE-II and Val-HeFT?
John JV McMurray

Since some drugs which block the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitors (ACE-I) and spironolactone have been shown to improve symptoms, decrease hospital admission rates and increase survival in patients with congestive heart failure, it has been postulated that angiotensin II receptor blockers (ARBs) will also have a beneficial role in heart failure management.
The theory that ARBs might block the RAS more effectively than ACE-I, by blocking the actions of angiotensin II (Ang II) irrespective of its pathway of generation, was tested in the ELITE II study, which compared losartan (50 mg o.d.) and captopril (50 mg t.d.s.) in 3152 patients with NYHA Class II-IV heart failure. Although losartan was better tolerated than the ACE-I, it was not shown to be more clinically effective. These results suggest that ARBs should not be used as an alternative means of RAS blockade in patients with CHF, unless ACE-I are not tolerated.
The Val-HeFT trial examined the effects of adding the ARB, valsartan, to standard CHF treatment, including an ACE-I in 93% patients, and so provided data on the impact of a combination of ACE-I and ARB in heart failure treatment. Although all-cause mortality was not altered, there was a 13% risk reduction in the combined morbidity/mortality endpoint, largely as a reflection of a 27% reduction in CHF hospitalisation. However, subgroup analyses have identified two possible concerns. First, there was a very large reduction in mortality/morbidity in the small number of patients who were not taking an ACE-I at baseline. Secondly, there was a trend towards an increase in mortality/morbidity in patients who were taking a beta-blocker at baseline. Further information on these important clinical questions will be provided by the ongoing VALIANT trial.
In the meantime, the totality of the currently available evidence suggests that ARBs may be useful in the treatment of patients who are intolerant of ACE-I, but should not be used as a general alternative to ACE inhibition in all CHF patients. In addition, in patients who are not taking a beta-blocker, addition of an ARB to an ACE-I seems to be an acceptable strategy. From the current evidence, it would appear that that ARBs should not be combined with an ACE-I and beta-blocker in the treatment of CHF.

JRAAS 2001;2:89-92.

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