“Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or nonserious atrial fibrillation was observed,” the FDA reported in a statement. “Additionally, increasing dose or duration of bisphosphonate therapy was not associated with an increase rate of atrial fibrillation.” The FDA will continue to monitor the situation.
Safety review of nearly 20,000 patients finds no causal link
To arrive at these conclusions, the FDA reviewed data on 19,687 patients treated with bisphosphonates and 18,358 patients treated with placebo who were followed for 6 months to 3 years. The risk of atrial fibrillation was low within each study. Specifically, most studies contained two or fewer cases of atrial fibrillation. Moreover, the absolute difference in event rates between each of the bisphosphonate and placebo arms varied from 0 to 3 per 1000.
“Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or nonserious atrial fibrillation was observed.”—US FDA
The investigation was spurred by two reports that found increased rates of serious atrial fibrillation in patients who took either Merck's Fosamax® (alendronate) or Novartis' Reclast® (zoledronic acid).
The following seven FDA-approved bisphosphonates are currently on the market: alendronate (sold generically and as Fosamax), ibandronate (Boniva®), risedronate (sold as Actonel®), zoledronic acid (Reclast and Zometa®), etidronate (Didronel®), pamidronate (Aredia®), and tiludronate (Skelid®).
In the FDA safety review, 1 large study of zoledronic acid showed a statistically significant increase in the rate of serious atrial fibrillation events, but there was no clear association seen between overall bisphosphonate exposure and the rate of serious or nonserious atrial fibrillation observed across all studies.
Translating research into practice
As a result of the new findings, “healthcare professionals should not alter their prescribing patterns for bisphosphonates and patients should not stop taking their bisphosphonate medication,” according to the FDA.
Going forward, the FDA is exploring the feasibility of conducting additional epidemiologic studies to examine this issue. The FDA is continuing to monitor postmarket reports of atrial fibrillation in patients who have taken bisphosphonates.
“I tell patients with current atrial fibrillation or a history of arrhythmia that there have been reports of bisphosphonate use being associated with an increased incidence of the arrhythmia, but that the largest population-based studies have not found such an association,” said Stephen Honig, MD, director of the osteoporosis center at New York University Hospital for Joint Diseases in New York City. “I prescribe bisphosphonates for such patients and have not seen any issue regarding their use since I first became aware of the Reclast data,” he told MSKreport.com. “I think the drugs have a good cardiac safety profile and may offer benefits regarding other cardiac conditions, but that data is not definitive to date.”
Reference
1. FDA home page. Medwatch. Available at: http://www.fda.gov/medwatch/safety/2008/safety08.htm#bisphosphonates2. Accessed November 18, 2008.
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