title: Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients Without Heart Failure? Insights From 254,301 Patients From Randomized Trials.
abstract: OBJECTIVE
  To compare the efficacy and safety of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in patients without heart failure.
  
  
  METHODS
  Meta-analysis of randomized trials identified using PubMed, Embase, and Cochrane Central Register of Controlled Trials searches from January 1, 1980, through April 13, 2015, of ACEis and ARBs compared with placebo or active controls and corroborated with head-to-head trials of ARBs vs ACEis. Outcomes were all-cause mortality, cardiovascular death, myocardial infarction (MI), angina, stroke, heart failure, revascularization, and new-onset diabetes.
  
  
  RESULTS
  Our search yielded 106 randomized trials that enrolled 254,301 patients. Compared with placebo, ACEis but not ARBs reduced the outcomes of all-cause mortality (ACEis vs placebo: relative risk [RR], 0.89; 95% CI, 0.80-1.00; ARBs vs placebo: RR, 1.01; 95% CI, 0.96-1.06; Pinteraction=.04), cardiovascular death (RR, 0.83; 95% CI, 0.70-0.99 and RR, 1.02; 95% CI, 0.92-1.14; Pinteraction=.05), and MI (RR, 0.83; 95% CI, 0.78-0.90 and RR, 0.93; 95% CI, 0.85-1.03; Pinteraction=.06). The meta-regression analysis revealed that the difference between ACEis and ARBs compared with placebo was due to a higher placebo event rate in the ACEis trials (most of these trials were conducted a decade earlier than the ARB trials) for the outcome of all-cause mortality (P=.001), cardiovascular death (P<.001), and MI (P=.02). Sensitivity analyses restricted to trials published after 2000 revealed similar outcomes with ACEis vs placebo and ARBs vs placebo (Pinteraction>.05). Head-to-head comparison trials of ARBs vs ACEis exhibited no difference in outcomes except for a lower risk of drug withdrawal due to adverse effects with ARBs (RR, 0.72; 95% CI, 0.65-0.81).
  
  
  CONCLUSIONS
  In patients without heart failure, evidence from placebo-controlled trials (restricted to trials after 2000), active controlled trials, and head-to-head randomized trials all suggest ARBs to be as efficacious and safe as ACEis, with the added advantage of better tolerability.
authors.affiliation: New York University School of Medicine, New York, NY. Electronic address: sripalbangalore@gmail.com.
authors.forename: Sripal
authors.initials: S
authors.lastname: Bangalore
authors.affiliation: New York University School of Medicine, New York, NY.
authors.forename: Robert
authors.initials: R
authors.lastname: Fakheri
authors.affiliation: Mount Sinai Beth Israel Medical Center, New York, NY.
authors.forename: Bora
authors.initials: B
authors.lastname: Toklu
authors.affiliation: New York University School of Medicine, New York, NY.
authors.forename: Gbenga
authors.initials: G
authors.lastname: Ogedegbe
authors.affiliation: New York University School of Medicine, New York, NY.
authors.forename: Howard
authors.initials: H
authors.lastname: Weintraub
authors.affiliation: University Hospital, Bern, Switzerland; Mount Sinai, Icahn School of Medicine, New York, NY.
authors.forename: Franz H
authors.initials: FH
authors.lastname: Messerli
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000453:epidemiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology; D006334:Heart Function Tests; D006801:Humans; D010043:Outcome and Process Assessment, Health Care; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors