Risk of myocardial infarction and abacavir therapy: no increased risk across 52 GlaxoSmithKline-sponsored clinical trials in adult subjects.
BACKGROUND
Recently, the Data collection of Adverse events of Anti-HIV Drugs Group (D:A:D) described results from their international observational cohort of 33,347 HIV-1-infected individuals, suggesting unexpected increased risk of myocardial infarction (MI) associated with abacavir (ABC) therapy [relative rate 1.9, 95% confidence interval (CI): 1.47 to 2.45; P = 0.0001]. To contribute to the scientific question, we summarized GlaxoSmithKline HIV clinical trial data to determine if a similar signal emerged.


METHODS
We compiled data from GlaxoSmithKline-sponsored clinical trials with > or = 24 weeks of combination antiretroviral therapy comprising 14,174 HIV-infected adults who received ABC (n = 9502; 7641 person-years) or not (n = 4672; 4267 person-years).


RESULTS
Baseline demographics and HIV disease characteristics, including lipids and glucose values, were similar. MI rates were comparable among subjects exposed [n = 16 (0.168%; CI: 0.096 to 0.273; 2.09 per 1000 person-years)] or not [n = 11 (0.235%; CI: 0.118 to 0.421; 2.57 per 1000 person-years)] to ABC-containing therapy. Results of 12 trials with randomization to ABC or not were consistent (2.15 per 1000 person-years vs. 4.10 per 1000 person-years).


CONCLUSIONS
In this pooled summary, we observed few MI events overall and no excess risk of MI with ABC therapy. It is unclear why results from this data set seem discrepant to the Data collection of Adverse events of Anti-HIV Drugs data set, particularly, as the non-ABC MI event rate is similar. Further data are needed to evaluate any association between ABC and increased risk of MI.
Brothers
Cindy H
CH
GlaxoSmithKline Infectious Disease Medicine Development Centre, Research Triangle Park, NC, USA.
Hernandez
Jaime E
JE
Cutrell
Amy G
AG
Curtis
Lloyd
L
Ait-Khaled
Mounir
M
Bowlin
Steve J
SJ
Hughes
Sara H
SH
Yeo
Jane M
JM
Lapierre
Didier H
DH
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003324:Coronary Artery Disease / Q000209:etiology; D003627:Data Interpretation, Statistical; D015224:Dideoxynucleosides / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology*; D012307:Risk Factors; D055815:Young Adult; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D000099227:Abacavir