title: Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group.
abstract: OBJECTIVE
  We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA).
  
  
  BACKGROUND
  Aspirin and ACEi both reduce mortality when given early after MI. Aspirin inhibits the synthesis of vasodilating prostaglandins, and, in principle, this inhibition might antagonize some of the effects of ACEi. But it is uncertain whether, in practice, this influences the effects of ACEi on mortality and major morbidity after MI.
  
  
  METHODS
  This overview sought individual patient data from all trials involving more than 1,000 patients randomly allocated to receive ACEi or control starting in the acute phase of MI (0-36 h from onset) and continuing for four to six weeks. Data on concomitant ASA use were available for 96,712 of 98,496 patients in four eligible trials (and for none of 1,556 patients in the one other eligible trial).
  
  
  RESULTS
  Overall 30-day mortality was 7.1% among patients allocated to ACEi and 7.6% among those allocated to control, corresponding to a 7% (standard deviation [SD], 2%) proportional reduction (95% confidence interval 2% to 11%, p = 0.004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence or absence of ASA (chi-squared for heterogeneity = 0.4 and 0.0, respectively; both not significant). Nor was there good evidence that the effects of ACEi on other clinical outcomes were changed by concomitant ASA use.
  
  
  CONCLUSIONS
  Both ASA and ACEi are beneficial in acute MI. The present results support the early use of ACEi in acute MI, irrespective of whether or not ASA is being given.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. latini@irfmn.mnegri.it
authors.forename: R
authors.initials: R
authors.lastname: Latini
authors.forename: G
authors.initials: G
authors.lastname: Tognoni
authors.forename: A P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: C
authors.initials: C
authors.lastname: Baigent
authors.forename: E
authors.initials: E
authors.lastname: Braunwald
authors.forename: Z M
authors.initials: ZM
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Collins
authors.forename: M
authors.initials: M
authors.lastname: Flather
authors.forename: M G
authors.initials: MG
authors.lastname: Franzosi
authors.forename: J
authors.initials: J
authors.lastname: Kjekshus
authors.forename: L
authors.initials: L
authors.lastname: Køber
authors.forename: L S
authors.initials: LS
authors.lastname: Liu
authors.forename: R
authors.initials: R
authors.lastname: Peto
authors.forename: M
authors.initials: M
authors.lastname: Pfeffer
authors.forename: F
authors.initials: F
authors.lastname: Pizzetti
authors.forename: E
authors.initials: E
authors.lastname: Santoro
authors.forename: P
authors.initials: P
authors.lastname: Sleight
authors.forename: K
authors.initials: K
authors.lastname: Swedberg
authors.forename: L
authors.initials: L
authors.lastname: Tavazzi
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D001241:Aspirin