Meta-analysis of combined therapy with angiotensin receptor antagonists versus ACE inhibitors alone in patients with heart failure

• Published in: PloS one 2010-04, Vol.5 (4), p.e9946
• Main Authors: Kuenzli, Andrea, Bucher, Heiner C, Anand, Inder, Arutiunov, Gregory, Kum, Leo C, McKelvie, Robert, Afzal, Rizwan, White, Michel, Nordmann, Alain J
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Angiotensin converting enzyme inhibitors; Angiotensin II; Angiotensin II Type 1 Receptor Blockers - adverse effects; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - adverse effects; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Angiotensins; Beta blockers; Cardiac patients; Cardiovascular agents; Cardiovascular Disorders/Heart Failure; Care and treatment; Clinical trials; Comparative analysis; Complications and side effects; Congestive heart failure; Data processing; Drug Therapy, Combination; Heart; Heart failure; Heart Failure - complications; Heart Failure - drug therapy; Heart Failure - mortality; Heterogeneity; Hospitalization; Humans; Hyperkalemia; Hypotension; Hypotension - chemically induced; Inhibitors; Meta-analysis; Mortality; Patients; Peptidyl-dipeptidase A; Pharmacology; Public Health and Epidemiology/Health Policy; Randomized Controlled Trials as Topic; Renal function; Renal Insufficiency - chemically induced; Risk; Risk Assessment; Subgroups; Survival Rate; Therapy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009946

There is insufficient evidence whether the benefit of adding angiotensin II receptor blockers (ARBs) to angiotensin-converting enzyme (ACE) inhibitors outweighs the increased risk of adverse effects in patients with heart failure. Two independent reviewers searched and abstracted randomized controlled trials of ARBs and ACE inhibitors compared to ACE inhibitor therapy alone in patients with heart failure reporting mortality and hospitalizations having a follow-up of at least 6 months identified by a systematic literature search. Eight trials including a total of 18,061 patients fulfilled our inclusion criteria. There was no difference between patients treated with combination therapy and ACE inhibitor therapy alone for overall mortality, hospitalization for any reason, fatal or nonfatal MI. Combination therapy was, however, associated with fewer hospital admissions for heart failure (RR 0.81, 95%CI 0.72-0.91), although there was significant heterogeneity across trials (p-value for heterogeneity = 0.04; I(2) = 57% [95%CI 0-83%]). Patients treated with combination therapy had a higher risk of worsening renal function and symptomatic hypotension, and their trial medications were more often permanently discontinued. Lack of individual patient data precluded the analysis of time-to-event data and identification of subgroups which potentially benefit more from combination therapy such as younger patients with preserved renal function and thus at lower risk to experience worsening renal function or hyperkalemia. Combination therapy with ARBs and ACE inhibitors reduces admissions for heart failure in patients with congestive heart failure when compared to ACE inhibitor therapy alone, but does not reduce overall mortality or all-cause hospitalization and is associated with more adverse events. Thus, based on current evidence, combination therapy with ARBs and ACE inhibitors may be reserved for patients who remain symptomatic on therapy with ACE inhibitors under strict monitoring for any signs of worsening renal function and/or symptomatic hypotension.