Bisphosphonates Not Linked to Atrial Fibrillation, Says FDA

The FDA reported Nov. 12 that, based on the results of clinical trials, no clear association between bisphosphonates and serious or nonserious atrial fibrillation, or AF, exists. The agency said, however, it would continue to track postmarketing reports of AF in patients who have taken these drugs.

In an update to an early communication issued last year about the cardiovascular safety profile of bisphosphonates, the agency stated that "across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or nonserious atrial fibrillation was observed." Even increasing the dosage and duration of treatment was not associated with an increased rate of the condition.

The FDA update concluded that, based on the information currently available, physicians "should not alter their prescribing patterns for bisphosphonates," and patients should not stop taking these medications.

FDA officials announced in October 2007 that they were reviewing data that had raised concerns about a potential increased risk for AF in patients with osteoporosis who had been treated with bisphosphonates. That review involved the following drugs:

To date, the sponsors of these medications have submitted data from several studies involving a total of 19,687 men and women treated with bisphosphonates and 18,358 patients who received placebos. The absolute difference in AF event rates between each of the bisphosphonate and placebo study arms varied from zero to three per 1,000.

In its update, the FDA acknowledged the discordance among previous studies, a number of which did suggest an increased risk of AF in postmenopausal women being treated for osteoporosis. Specifically, one large study of zoledronic acid showed a "statistically significant" increase in the rate of serious AF events. The agency said it would explore the feasibility of conducting additional epidemiologic studies to examine this issue. Meanwhile, the update noted, the agency will continue to monitor reports of AF in patients who have taken bisphosphonates.

FDA officials urge physicians to report side effects from the use of bisphosphonates online or by calling (800) 332-1088.