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No Association of Abacavir Use With Myocardial Infarction: Findings of an FDA Meta-Analysis

Ding, Xiao PhD*; Andraca-Carrera, Eugenio PhD*; Cooper, Charles MD; Miele, Peter MD; Kornegay, Cynthia PhD§; Soukup, Mat PhD*; Marcus, Kendall A. MD

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 1st, 2012 - Volume 61 - Issue 4 - p 441–447
doi: 10.1097/QAI.0b013e31826f993c
Clinical Science

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.

Office of *Biostatistics

Translational Sciences

Anti-Infective Products

§Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD.

Correspondence to: Kendall A. Marcus, MD, Office of Anti-Infective Products, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD (e-mail: kendall.marcus@fda.hhs.gov).

The authors have no funding or conflicts of interest to disclose.

Presented at 18th Conference on Retroviruses and Opportunistic Infections, February 27–March 2, 2011, Boston, MA (Abstract #808).

Received January 7, 2012

Accepted August 16, 2012

© 2012 Lippincott Williams & Wilkins, Inc.