Meta-analyses of mortality and morbidity effects of an angiotensin receptor blocker in patients with chronic heart failure already receiving an ACE inhibitor (alone or with a beta-blocker)

Background: While treatment with either angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) is clearly superior to placebo in the treatment of heart failure patients, controversy still surrounds the effects of ARBs in patients already receiving an ACEi. Even more controversial is the wisdom of administering ARBs in patients already on an ACEi and β-blocker. Methods: We present meta-analyses of the available randomised controlled trials to date (October 2003) of angiotensin II receptor antagonists versus placebo in patients with symptomatic chronic heart failure in which both groups received ACEi. The two largest eligible trials were CHARM-Added and Val-HeFT. We examined two endpoints: mortality and a combined endpoint of mortality and morbidity. Results: In the first meta-analysis, covering all patients regardless of β-blocker use, we found a significant reduction in the combined endpoint (odds ratio [OR]=0.89; 95% confidence interval [CI] 0.81–0.98), but no significant reduction in mortality itself (OR=0.97; CI: 0.87–1.08). In the second meta-analysis, covering patients concomitantly on β-blockers, we found no significant effect on mortality (OR=1.08; CI: 0.90–1.29) or on the combined endpoint (OR=0.94; CI: 0.82–1.10). In the third meta-analysis, covering patients not on concomitant β-blockers, there is clear evidence of a reduction in the combined endpoint (OR=0.83; CI: 0.73–0.94), but not on mortality (OR=0.93; CI: 0.81–1.06). Conclusion: There is now good evidence for the use of ARBs to prevent events in patients with heart failure on ACEi who are not suitable for β-blockers.