title: Meta-analysis of combined therapy with angiotensin receptor antagonists versus ACE inhibitors alone in patients with heart failure.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kuenzli
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.forename: Inder
authors.initials: I
authors.lastname: Anand
authors.forename: Gregory
authors.initials: G
authors.lastname: Arutiunov
authors.forename: Leo C
authors.initials: LC
authors.lastname: Kum
authors.forename: Robert
authors.initials: R
authors.lastname: McKelvie
authors.forename: Rizwan
authors.initials: R
authors.lastname: Afzal
authors.forename: Michel
authors.initials: M
authors.lastname: White
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Nordmann
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000139:chemically induced; D018570:Risk Assessment; D015996:Survival Rate
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors