New research uses high-quality data to find that type 2 diabetes drug rosiglitazone increases by 33 per cent the risk of adverse cardiovascular events.
Rosiglitazone is a drug developed originally for the treatment of type 2 diabetes. It was approved in 1999 by the United States Food and Drug Administration (FDA) under the name Avandia.
While Europe has suspended the drug because of concerns about its adverse effects on heart health, and the United States has restricted its use, research on its safety has produced mixed results so far.
Now, a new study that appears in the journal The BMJ has used more reliable data to investigate the cardiovascular health effects of this drug.
The new paper’s lead author is Joshua D. Wallach, who is an assistant professor in the Department of Environmental Health Sciences at the Yale School of Public Health in New Haven, CT.
The need for more accurate data
In 1999, a year ahead of Europe, the FDA approved rosiglitazone, states Wallach and the colleagues in their paper.
Regulatory bodies warned as early as 2006 about its potential effects on heart failure and a meta-analysis of several trials indicated a 43 percent higher risk of heart attack in 2007.
As a result, the drug was taken off European markets by 2010, because the risk of heart attack and stroke was increased.
The drug is still available in the U.S., though it features warnings on its packaging, and in 2010-2011 the FDA restricted its availability.
The fact that the drug is still available is due primarily to the mixed results produced by the cardiovascular effects of the drug investigation.
The new research, however, indicates that these mixed results are due to the poor nature of the data used by those previous studies.
In other words, these previous articles did not have access to “individual patient data (IPD),” that is, raw data, such as patient medical records, instead of summary-level data, which are, for example, the final results of clinical trials.
Studying rosiglitazone and heart health
Wallach and colleagues set out to evaluate more than 130 clinical trials to rectify this methodological problem; the researchers had access to IPD for 33 of those trials. This totaled 48,000 patient data for adults, of which 21,156 were IPDs for researchers.
The clinical trials were randomized, phase II-IV controlled trials that had studied and compared the effects of rosiglitazone with any other controls for at least 24 weeks.
“The control group was defined as patients who received any other drug regimen than rosiglitazone, including placebo,” the researchers explain.
In their study of the trials for which they had IPD, the team analyzed the outcomes of “acute myocardial infarction, heart failure, cardiovascular-related death and non-cardiovascular-related death.”
The researchers only investigated myocardial infarction and cardiovascular-related death for the other trials, using summary-level data.
A 33% higher risk of cardiovascular disease
The analysis revealed a 33 per cent higher risk of heart attack, heart failure, cardiovascular deaths, and combined non-cardiovascular deaths among people taking the drug relative to those taking any control substance, like placebo.
Wallach and his fellow Members conclude:
“The results suggest that rosiglitazone is associated with an increased cardiovascular risk, especially for heart failure events.”
The results also help to underline the significance of using raw data to accurately assess a drug’s health, the authors say.
“Our study suggests that IPD may be appropriate to accurately identify all adverse events when evaluating drug safety and conducting safety-focused meta-analyses,” they write.
“By including this data in research, patients, physicians and researchers would be able to make more informed decisions on the safety of treatments.”
“Our study highlights the need for independent evidence review to encourage accountability and maintain trust in approved therapies, and post-market monitoring that monitors known and unknown risks and benefits.”