Bisphosphonates and atrial fibrillation: clinical trial data suggest possible link

In 2007, an article describing an American placebo-controlled clinical trial of yearly zoledronic acid infusion at a dose of 5 mg mentioned a statistically significant excess of severe atrial fibrillation in postmenopausal women. Bisphosphonates had not previously been linked to this adverse effect. Several meta-analyses of clinical trials have been published, but they covered only a small number of the hundreds of comparative trials evaluating bisphosphonates, few of which mentioned atrial fibrillation. In 2010, a meta-analysis of placebo-controlled trials of bisphosphonates, in a total of 26 126 patients with osteoporosis, showed an increased risk of severe atrial fibrillation. A larger meta-analysis (40104 women) showed a nonsignificant increase in the risk of atrial fibrillation, regardless of severity. A meta-analysis published in 2010 included 7 placebo-controlled observational studies of bisphosphonates in patients with osteoporosis, two of which showed an increased risk of severe atrial fibrillation. This meta-analysis showed no statistically significant increase in the overall risk of severe atrial fibrillation. Our literature search, up to mid-2010, found no studies concerning the risk of atrial fibrillation in cancer patients treated with bisphosphonates. No cardiac adverse effects were mentioned in a report analysing two trials in patients with Paget's disease. Pending the publication of more data, the potential risk of severe atrial fibrillation in some patients treated with bisphosphonates should be taken into account. There is no evidence of an increased risk with a specific bisphosphonate, route of administration, patient subpopulation, or treatment duration.