ARBs demonstrate no beneficial effect on mortality in patients with heart failure

Key Points

A systematic search of the literature published in the International Journal of Clinical Practice demonstrated that angiotensin receptor blockers (ARBs) used as monotherapy or in combination with angiotensin-converting enzyme (ACE) inhibitors are not associated with a beneficial effect on mortality in patients with heart failure (HF). ARBs added to ACE inhibitors did significantly reduce the rate of hospitalizations because of worsening HF.

The investigators carried out a search of the literature using MEDLINE records from 1980 to 2007. Trials were included if they were randomized, controlled studies with >500 patients and with follow-up of >6 months and if total mortality rates and/or rates of hospital admission because of worsening HF were available. Data were retrieved by 2 independent reviewers, and disagreements were resolved by a third reviewer.

A total of 175 studies were reviewed, and 7 trials were included in the final analysis. The trials evaluated the effects of either ARBs plus ACE inhibitors versus ACE inhibitors alone or ARBs alone versus ACE inhibitors alone on the rates of mortality and/or hospitalization because of worsening HF. Post-myocardial infarction (MI) trials were also included. Mortality data were available for 27,495 patients. Across the studies, mean patient age ranged from 63 to 74 years, and the majority of patients had New York Heart Association (NYHA) class II to IV HF. The median follow-up ranged from 43 to 164 weeks.

In trials that evaluated hospitalizations because of worsening HF in patients treated with either ARBs plus ACE inhibitors or ACE inhibitors alone, 1,504 hospitalizations occurred among 7,999 patients (ARBs plus ACE inhibitors, 686 hospitalizations; ACE inhibitors alone, 818 hospitalizations). The pooled RR for hospitalizations among patients treated with ARBs plus ACE inhibitors was 0.83 (95% CI, 0.71–0.97), which correlates with a significant 17% RR reduction in hospital admissions (P=.02). Among patients treated with either ARBs alone or ACE inhibitors alone, there were 654 hospital admissions among 4,310 patients (ARBs, 333 hospitalizations; ACE inhibitors, 321 hospitalizations). In patients treated with ARBs, the pooled RR for hospitalizations was 1.09 (95% CI, 0.74–1.6).

In trials that evaluated patients who were post-MI, 2,885 deaths were reported among 15,295 patients (ARBs alone, 1,478 deaths; ACE inhibitors alone, 1,407 deaths; pooled RR for ARBs alone, 1.05; 95% CI, 0.97–1.14).

The authors pointed out that their study was potentially limited by the possibility of publication bias, use of tabular data, retrospective analysis, missing data, and heterogeneity of the included studies.

They suggested that although ARBs are effective in reducing the rate of hospitalizations among patients with chronic HF who are already taking ACE inhibitors, these agents do not have an additional beneficial effect on mortality. They concluded that "ARBs should be considered for reducing hospitalizations in patients with frequent visits to the hospital because of decompensation of HF," although they suggested that an economic analysis is needed to determine the potential effects of this change on the healthcare system.

SOURCE

Shibata MC, Tsuyuki RT, Wiebe N. The effects of angiotensin-receptor blockers on mortality and morbidity in heart failure: A systematic review. Int J Clin Pract. 2008;62:1397–1402.