Individual Patient Level Data Clarifies Rosiglitazone Cardiovascular Risk
ROSIGLITAZONE is used to help control blood sugar levels in patients with Type 2 diabetes mellitus; however, the use of the drug has been suspended in Europe and has previously been restricted in the USA due to concerns over the risk of serious heart problems. Since 2007, there have been conflicting findings regarding the incidence of heart attacks associated with the drug’s use. Now, a team of researchers from Yale University and New York University have used individual patient-level data (IPD) to provide clarity over the relationship between rosiglitazone and the risk of cardiovascular events.
In the most comprehensive study of its kind, the results from more than 130 trials involving 48,000 adult patients that compared rosiglitazone with any control for at least 24 weeks were analysed (IPD were available for 33 trials, which included 21,156 patients). Previously, safety analyses have been conducted mostly relying on summary level data (e.g., results reported in publications and clinical trial registries) instead of the raw data. The IPD were made available to external investigators by GlaxoSmithKline, the maker of rosiglitazone.
Using data from 274 events among 11,837 rosiglitazone patients and 219 among 9,319 control patients, the researchers found that rosiglitazone was associated with a 33% increased risk of a composite cardiovascular event (heart attack, heart failure, cardiovascular and non-cardiovascular-related death) occurring compared with controls.
The researchers then examined the cardiovascular events independently and found that there were higher estimates of the risk of heart attacks with the use of IPD from the 33 GSK trials compared with trials with IPD and summary level data. The researchers comment that this potential difference in results highlights the need to analyse different data sources; they also call for greater clinical trial transparency and data sharing to accurately assess the safety of drugs.
“Our study suggests that when evaluating drug safety and performing meta-analyses focussed on safety, IPD might be necessary to accurately classify all adverse events,” they wrote. “By including these data in research, patients, clinicians, and researchers would be able to make more informed decisions about the safety of interventions.”
They added: “Our study highlights the need for independent evidence assessment to promote transparency and ensure confidence in approved therapeutics, and postmarket surveillance that tracks known and unknown risks and benefits.”