Summary and Introduction
Summary
Background: Trials evaluating angiotensin-receptor blockers in heart failure (HF) have shown inconsistent results.
Objective: To evaluate the effect of angiotensin II (AII) receptor blockers in HF patients on total mortality and HF hospitalisations.
Methods: Systematic search of the literature through MEDLINE (1980-2007) and abstracts of major cardiovascular congresses from 2002 to 2007. Eligibility criteria: (i) randomised controlled trials with more than 500 patients and follow up > 6 months, (ii) availability of total mortality and/or (iii) availability of hospital admission because of worsening HF. Data retrieved by two independent reviewers. DerSimonian random effects model was used.
Results: Mortality data were available from 27,495 patients. When AII receptor blockers plus angiotensin-converting enzyme inhibitors (ACE-I) were compared with ACE-I in chronic HF trials, the relative risk (RR) for death was 0.98 (95% CI: 0.84-1.15). When AII receptor blockers were compared with ACE-I the RR for death was 1.06 (95% CI: 0.56-1.62). Similar results were found for postmyocardial infarction trials. The effects on hospital admission revealed a RR of 0.83 (95% CI: 0.71-0.97) and 1.09 (95% CI: 0.74-1.60) respectively.
Conclusion: Angiotensin II receptor blockers did not show any beneficial effect on mortality when used in combination with ACE-I or when compared with ACE-I alone. A 17% reduction in hospital admissions was observed.
Introduction
Heart failure (HF) is a major burden to health care and society. It affects about 1% of the population and its prevalence is increasing. This is likely because of advances in the treatment of myocardial infarction (MI) and an ageing population.
The use of angiotensin-converting enzyme inhibitors (ACE-I) has been shown to decrease the level of circulating angiotensin II (AII). However, AII is not consistently suppressed after chronic use of ACE-I. This is thought to be due to other sources for the production of AII, independent of ACE pathway. However, despite the incomplete suppression of AII with ACE-I, its beneficial effect on important clinical end-points in patients with HF persists. This gave rise to the notion that blockade of AII receptor, a final pathway for the action of AII, would have important effect on morbidity and mortality, perhaps greater than ACE-I. This hypothesis was evaluated in several randomised clinical trials with adequate power to address important clinical end-points. Careful evaluation of the trials revealed that the magnitude of the effect on mortality was of borderline clinical and statistical significance. Therefore, a more precise evaluation of the magnitude of the treatment effect of AII type 1 receptor blockers (ARBs) on morbidity and mortality is warranted.
Meta-analysis is a tool that can be used to more precisely evaluate the effect of a treatment. By plotting and synthesising data from several clinical trials addressing similar questions, a more precise estimate of treatment effect can be obtained. We aimed to systematically review the effect of ARBs on mortality and HF hospital admissions.