title: Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients.
abstract: OBJECTIVE
  Renin-angiotensin-aldosterone system (RAAS) inhibitors are well established for the reduction in cardiovascular morbidity, but their impact on all-cause mortality in hypertensive patients is uncertain. Our objective was to analyse the effects of RAAS inhibitors as a class of drugs, as well as of angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockers (ARBs) separately, on all-cause mortality.
  
  
  RESULTS
  We performed a pooled analysis of 20 cardiovascular morbidity-mortality trials. In each trial at least two-thirds of the patients had to be diagnosed with hypertension, according to the trial-specific definition, and randomized to treatment with an RAAS inhibitor or control treatment. The cohort included 158 998 patients (71 401 RAAS inhibitor; 87 597 control). The incidence of all-cause death was 20.9 and 23.3 per 1000 patient-years in patients randomized to RAAS inhibition and controls, respectively. Overall, RAAS inhibition was associated with a 5% reduction in all-cause mortality (HR: 0.95, 95% CI: 0.91-1.00, P= 0.032), and a 7% reduction in cardiovascular mortality (HR: 0.93, 95% CI: 0.88-0.99, P= 0.018). The observed treatment effect resulted entirely from the class of ACE inhibitors, which were associated with a significant 10% reduction in all-cause mortality (HR: 0.90, 95% CI: 0.84-0.97, P= 0.004), whereas no mortality reduction could be demonstrated with ARB treatment (HR: 0.99, 95% CI: 0.94-1.04, P= 0.683). This difference in treatment effect between ACE inhibitors and ARBs on all-cause mortality was statistically significant (P-value for heterogeneity 0.036).
  
  
  CONCLUSIONS
  In patients with hypertension, treatment with an ACE inhibitor results in a significant further reduction in all-cause mortality. Because of the high prevalence of hypertension, the widespread use of ACE inhibitors may result in an important gain in lives saved.
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus MC, 's Gravendijkwal 230, 3015 GE Rotterdam, The Netherlands. l.vanvark@erasmusmc.nl
authors.forename: Laura C
authors.initials: LC
authors.lastname: van Vark
authors.forename: Michel
authors.initials: M
authors.lastname: Bertrand
authors.forename: K Martijn
authors.initials: KM
authors.lastname: Akkerhuis
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Brugts
authors.forename: Kim
authors.initials: K
authors.lastname: Fox
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Mourad
authors.forename: Eric
authors.initials: E
authors.lastname: Boersma
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002423:Cause of Death; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents