BACKGROUND AND PURPOSE:

• Rosiglitazone (brand name Avandia) is an FDA-approved drug for type 2 diabetes
• Safety issues related to CVD risk have reduced use in the US and resulted in a European ban
• Wallach et al. (BMJ, 2019) analyzed rosiglitazone treatment and its impact on cardiovascular risk

METHODS:

• Systematic review and meta-analysis
• Data sources
  • GlaxoSmithKline’s (GSK’s) ClinicalStudyDataRequest.com for individual patient level data (IPD) and Study Register platforms
  • MEDLINE, PubMed, Embase, Web of Science, Cochrane Central Registry of Controlled Trials, Scopus, and ClinicalTrials.gov from inception to January 2019
• Study inclusion criteria
  • RCTs (phase II-IV clinical trials)
  • Minimum 24 week use in adults
• Outcomes
  • Composite outcome (where IPD were available)
    • Acute myocardial infarction | Heart failure | Cardiovascular related death | Non-cardiovascular related death
  • Also analyzed the above events independently (secondary analyses)
  • Summary-level data analysis (where IPD not available)
    • Myocardial infarction
    • Cardiovascular related death

RESULTS:

• 33 trials with IPD available | 21,156 patients
• 103 trials without IPD
  • 23,683 patients included in myocardial infarction group
  • 22,772 patients included in the cardiovascular related death group

IPD data

• IPD data: Rosiglitazone use was associated with a 33% increased risk of a composite event vs controls
  • Odds ratio (OR) 1.33 (95% CI, 1.09 to 1.61)
• Secondary individualized outcomes
  • Myocardial infarction: OR 1.17 (95% CI, 0.92 to 1.51)
  • Heart failure: OR 1.54 (95% CI, 1.14 to 2.09)
  • Cardiovascular related death: OR 1.15 (95% CI, 0.55 to 2.41)
  • Non-cardiovascular related death: OR 1.18 (95% CI, 0.60 to 2.30)

Summary data added to IPD data

• Risks were attenuated for the following
• Myocardial infarction: OR 1.09 (95% CI, 0.88 to 1.35)
• Cardiovascular related death: OR 1.12 (95% CI, 0.72 to 1.74)

CONCLUSION:

• Results of this study indicate that rosiglitazone is associated with increased cardiovascular risk, mostly driven by heart failure and not myocardial infarction
• Restrictions for rosiglitazone use have eased since 2013
  • Pioglitazone is preferred in the US (and is also associated with increased risk of heart failure)
• The authors point out the importance of data transparency and that safety data may incomplete in trials

Rosiglitazone provides an ideal case to assess the impact of using IPD for safety related meta-analyses that examine relatively rare adverse events

Learn More – Primary Sources:

Updating insights into rosiglitazone and cardiovascular risk through shared data: individual patient and summary level meta-analyses

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