Angiotensin receptor blockers for heart failure

Evidence Summaries

Level of Evidence = B
In patients with heart failure, total mortality and total hospitalizations appear to be similar with angiotensin receptor blockers and ACE inhibitors.

The quality of evidence is downgraded by study limitations (unclear allocation concealment).

A Cochrane review 1 included 24 studies with a total of 25,051 subjects with symptomatic heart failure. Twenty-two studies randomised 17,900 patients with LVEF ≤40% and 2 studies randomised 7,151 patients with LVEF >40%.

LVEF ≤40% (mean study duration 2.2 years): Angiotensin receptor blockers (ARBs) did not reduce total morbidity as measured by total hospitalisations (RR 0.9, 95% CI 0.88 to 1.01; 2 studies, n=2,298) compared with placebo. The observed reduction in total mortality was of borderline statistical significance (RR 0.87, 95% CI 0.76 to 1.00; 9 studies, n=4,643). Total mortality (RR 1.05, 95% CI 0.91 to 1.22; 8 studies, n=5,201), total hospitalisations (RR 1.00, 95% CI 0.92 to 1.08; 4 studies, n=4,310), myocardial infarction (RR 1.0, 95% CI 0.62 to 1.63; 2 studies, n=3,874), and stroke (RR 1.63, 95% CI 0.77 to 3.44; 1 study, n=3,152) did not differ between ARBs and ACE inhibitors (ACEIs) but withdrawals due to adverse effects were lower with ARBs (RR 0.63, 95% CI 0.52 to 0.76; 6 studies, n=3,511). Combinations of ARBs plus ACEIs increased the risk of withdrawals due to adverse effects (RR 1.34, 95% CI 1.19 to 1.51; 4 studies, n=7,703) but did not reduce total mortality or total hospital admissions versus ACEI alone.

LVEF >40% (2 studies, n=7151; mean study duration 3.7 years): ARBs did not reduce total mortality (RR 1.02, 95% CI 0.93 to 1.12) or total morbidity as measured by total hospitalisations (RR 1.00, 95% CI 0.97 to 1.05) compared with placebo.

ACE inhibitor should be the first choice in heart failure patients and ARBs remain recommended as an alternative in patients intolerant of an ACE inhibitor.

The finding in the present review that ARBs are not effective in terms or mortality and morbidity versus placebo is surprising and inconsistent with the finding that ACE inhibitors and ARBs are not different when compared directly.

References

1. Heran BS, Musini VM, Bassett K et al. Angiotensin receptor blockers for heart failure. Cochrane Database Syst Rev 2012;(4):CD003040.  [PMID:22513909]

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