The research conducted by the Yale School of Public Health is the most comprehensive study of cardiovascular risk of rosiglitazone ever done. Originally created to control blood sugar levels in patients with type 2 diabetes, Rosiglitazone has now been shown to increase the risk of serious heart problems. This new information has led to the suspension of the drug in Europe and previous restrictions on its use in the United States.
“Since 2007, studies have reported conflicting findings about whether rosiglitazone increases the risk of heart attacks,” said Joshua Wallach, assistant professor at the Yale School of Public Health and the study’s lead author. “However, these studies did not have access to the raw data, also known as individual patient level data (IPD), from clinical trials, which are more reliable when estimating a drug’s true safety profile.”
Transparency of Testing
GlaxoSmithKline (GSK), rosiglitazone’s manufacturer, has recently made efforts to make IPD available to external investigators, making it easier for U.S. researchers to analyze raw clinical data and clarify some of the uncertainties surrounding the cardiovascular risk of the popular drug. Because of this, Wallach and his co-authors were able to analyze the results of more then 130 trials involving over 48,000 adult patients that compared rosiglitazone with any control for at least 24 weeks.
From the results of the trials, it was 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) compared with controls. Participants in the trials had 274 events which were among the 11,837 rosiglitazone patients and 219 events among 9,319 control patients.
When examined independently, the GlaxoSmithKline trials showed that IPD resulted in higher estimates of the risk of heart attacks than the analyses of trials with IPD and summary level data. The difference results from these data sources help to highlights the importance 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 focused on safety, IPD might be necessary to accurately classify all adverse events,” the researchers said.
“By including these data in research, patients, clinicians, and researchers would be able to make more informed decisions about the safety of interventions.”
“Although rosiglitazone is no longer available in Europe, and now rarely prescribed in the U.S., the rosiglitazone story is an important lesson in the value of clinical trial transparency” said Wallach. “Our study demonstrates how data-sharing platforms can be used to improve our understanding of drug safety.”