Abacavir Use and Risk for Myocardial Infarction and Coronary Artery Disease: Meta-analysis of Data from Clinical Trials (207263)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Other
• If ‘other’, further details on the scope of the study:
  Meta-analysis
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Systematic review and meta-analysis

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  ABACAVIR
• Medical condition to be studied:
  Human immunodeficiency virus transmission

Population studied

• Short description of the study population:
  For the current meta-analysis, studies were identified through the GSK clinical trial repository. Studies that have been conducted since the 2009 meta-analysis, and for which at least the primary objective had been completed by Dec 2016 were eligible. Similar to the previous meta-analysis, only studies that included at least 24 weeks exposure to cART, with ABC in the active treatment or comparator arm, were selected for inclusion in the meta-analysis. All included subjects were at least 18 years of age, and women of child-bearing potential were only included if on contraception to prevent pregnancy. Subjects in all included trials had been on cART for less than 14 days after their HIV diagnosis – except in ASSURE (EPZ113734) and STRIVING (201147), in which patients were required to have been on at least 6 months of treatment or switched regimens. Three studies (ARIES, ASSERT and HEAT) did not allow patients to have previously taken any nucleoside analog reverse-transcriptase inhibitors (NRTI) and/or non-nucleoside reversetranscriptase inhibitors (NNRTI) and/or protease inhibitors (PI). ARTs taken by subjects prior to entering a GSK/ViiV Healthcare-sponsored study were ignored in this metaanalysis, and cardiac events were not necessarily an exclusion criteria for the clinical trials.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Immunocompromised
• Estimated number of subjects:
  20000

Study design details

• Main study objective:
  To estimate the exposure adjusted incidence rate and relative rate of myocardial infarction (MI) and coronary artery disease (CAD) events reported in subjects treated with abacavir (ABC)-containing combination antiretroviral therapy (cART) regimens and in subjects treated with non-ABC-containing cART regimens.
• Outcomes:
  Occurrence of MI and CAD based on MedDRA high-level terms
• Data analysis plan:
  This meta-analysis will combine data from studies that were randomized to ABC or control, from studies included in a previous meta-analysis (Brothers et al. 2009) as well as from GSK/VH-sponsored studies identified post-2009. Percentages will be based on the frequency of adverse events collected during the conduct of clinical trials. Exposure adjusted incidence rates per 1,000 person-years will be calculated, and Poisson regression models will used to calculate unadjusted relative rates, but no adjustment for confounders will be performed. 95% confidence intervals will be calculated for rates and relative rates.