FDA restricts rosiglitazone use
European Medicines Agency suspends marketing authorization.
The FDA has announced that it will restrict use of the diabetes drug rosiglitazone to patients with type 2 diabetes who cannot control their diabetes with other medications, according to a press release.
In a separate announcement, the European Medicines Agency (EMA) has recommended suspending the marketing authorization of all rosiglitazone-containing antidiabetes medicines, including Avandia, Avandamet and Avaglim. Plans to phase out the drug’s availability in Europe within the next few months are in place.
“Both the FDA and the EMA have evaluated the same evidence and reached similar conclusions. Our different approaches in part reflect differences in the tools we have available to manage [the] risk and benefits of [the] medication,” Margaret A. Hamburg, MD, FDA commissioner, said during a conference call.
Rosiglitazone (Avandia, GlaxoSmithKline) will still be available in the United States, but the FDA will require GlaxoSmithKline to develop a restricted access program for the drug under a Risk Evaluation and Mitigation Strategy. Under the strategy, current rosiglitazone users who are benefiting from the drug will be able to continue taking it. Only patients who could not achieve glucose control with other medications and are unable to take pioglitazone (Actos, Takeda) will be able to take rosiglitazone. As previously reported by Cardiology Today, the FDA announced it would be evaluating preliminary results from a long-term, observational study suggesting patients who were taking pioglitazone may be at increased risk for bladder cancer. As of press time, no association had been confirmed.
“However, because of concerns of cardiovascular ischemia, physicians and health care professionals may want to consider switching patients to a different medication,” Joshua Sharfstein, MD, FDA principal deputy commissioner, said during the call.
In all cases, physicians must attest to and document their patients’ eligibility for taking the drug, and patients must review statements regarding the CV safety of rosiglitazone and acknowledge they understand the risks.
Both agencies’ decisions come in light of reviews that linked the medicines with an elevated risk for adverse CV events. Previous clinical trials, observational studies and meta-analyses of existing research from the past 3 years denoted a potential association between the medications and increased risk for ischemic heart disease, HF and fluid retention. Consequently, restrictions for the medications’ use in people with HF or a history of HF were implemented after market approval.
The FDA also ordered GlaxoSmithKline to convene an independent group of scientists to review key aspects of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, which compared the CV safety of rosiglitazone to other diabetes drugs. An earlier review noted a potential bias in the identification of CV events. In July, the U.S. Senate Committee on Finance accused GlaxoSmithKline of withholding scientific data pertaining to the drug.
Further, the FDA halted the company’s Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) trial, which compared rosiglitazone with pioglitazone and other diabetes drugs, and rescinded all regulatory deadlines for the completion of the trial.
In Europe, the EMA said it could not pinpoint further measures that would reduce CV risk. Unless GlaxoSmithKline can offer solid evidence that identifies a patient population in whom the drugs’ benefits would outweigh the risks, the suspension will hold.
The European Commission has also been notified of the committee’s recommendation for the adoption of a legally binding decision.
The EMA also advises patients who are currently taking these medications to consult their physicians to find alternative treatments. They should not, however, discontinue treatment before speaking with their doctors.
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PARTNER: TAVI in high-risk surgical patients linked with reduced mortality rates
Although an association between transcatheter aortic valve implantation and improved mortality was reported, it came at the price of increased stroke incidence
Transcatheter aortic valve implantation was associated with reduced mortality in patients who were at heightened risk for conventional valve replacement surgery, newly published results from the PARTNER trial suggested.
Researchers enrolled 358 patients who had aortic stenosis, cardiac symptoms and who were deemed unsuitable for conventional valve replacement surgery, which included balloon aortic valvuloplasty. Patients were randomly assigned to two cohorts: those who were at high risk for surgery but who received standard therapy (n=179) and those at high risk for surgery and underwent transcatheter aortic valve implantation (TAVI; n=179). The primary study endpoint was the rate of death from any cause during the study period
According to the results, a Kaplan-Meier analysis showed that 1-year rate of death from any cause was 30.7% in the TAVI group vs. 50.7% with standard therapy (HR with TAVI=0.55; 95% CI, 0.40-0.70). The composite endpoint of death from any cause or repeat hospitalization was also lower in the TAVI group vs. the standard therapy group (42.5% vs. 71.6%; HR=0.46; 95% CI, 0.35-0.59). The rate of cardiac symptoms was lower at 1 year in patients who underwent TAVI vs. those who received standard therapy (25.2% vs. 58%; P<.001).
Despite improvements in death from any cause and other endpoints, TAVI was also associated with an elevated incidence of major strokes vs. standard therapy (5% vs. 1.1%; P=.06), as well as an increase in the incidence of vascular complications (16.2% vs. 1.1%; P<.001).
“Although we were optimistic about the results of the trial, it ended up exceeding our expectations,” Michael Mack, MD, a study co-author and vice president of the Society of Thoracic Surgeons, told Cardiology Today. “Although this trial was unprecedented because we have randomized data available for the first time, just about as important will be the data from cohort A, which will be available in the spring, because that will compare the results with those of conventional surgery.”
Mack said the results will likely have a positive effect on the incorporation of the procedure into practice.
“This trial being positive will positively influence and catalyze the adoption of the procedure, but what it won’t do is change the regulatory process, and that will have to play out,” he said. “What it will do, though, is increase the enthusiasm for the procedure. If this trial was negative, it would have significantly negatively impacted the whole field.” – by Eric Raible
Leon M. N Engl J Med. 2010;doi:10.1056/NEJMoa1008232.