title: No association of abacavir use with myocardial infarction:  findings of an FDA meta-analysis.
abstract: BACKGROUND
  Several studies have reported an association between abacavir (ABC) exposure and increased risk of myocardial infarction (MI) among HIV-infected individuals. Randomized controlled trials (RCTs) and a pooled analysis by GlaxoSmithKline, however, do not support this association. To better estimate the effect of ABC use on risk of MI, the US Food and Drug Administration (FDA) conducted a trial-level meta-analysis of RCTs in which ABC use was randomized as part of a combined antiretroviral regimen.
  
  
  METHODS
  From a literature search conducted among 4 databases, 26 RCTs were selected that met the following criteria: conducted in adults, sample size more than 50 subjects, status completed, not a pharmacokinetic trial, and not conducted in Africa. The Mantel-Haenszel method, with risk difference and 95% confidence interval, was used for the primary analysis, along with additional alternative analyses, based on FDA-requested adverse event reports of MI provided by each investigator.
  
  
  RESULTS
  The 26 RCTs were conducted from 1996 to 2010, and included 9868 subjects (5028 ABC and 4840 non-ABC). Mean follow-up was 1.43 person-years in the ABC group and 1.49 person-years in the non-ABC group. Forty-six (0.47%) MI events were reported [24 (0.48%) ABC and 22 (0.46%) non-ABC], with no significant difference noted between the 2 groups (risk difference of 0.008% with 95% confidence interval: -0.26% to 0.27%).
  
  
  CONCLUSIONS
  To the best of our knowledge, our study represents the largest trial-level meta-analysis to date of clinical trials in which ABC use was randomized. Our analysis found no association between ABC use and MI risk.
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ding
authors.forename: Eugenio
authors.initials: E
authors.lastname: Andraca-Carrera
authors.forename: Charles
authors.initials: C
authors.lastname: Cooper
authors.forename: Peter
authors.initials: P
authors.lastname: Miele
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kornegay
authors.forename: Mat
authors.initials: M
authors.lastname: Soukup
authors.forename: Kendall A
authors.initials: KA
authors.lastname: Marcus
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic; D014481:United States; D014486:United States Food and Drug Administration; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D000099227:Abacavir