Meta-analysis Links Bisphosphonates to Atrial Fibrillation
Data from a recent meta-analysis suggest that use of bisphosphonates for treatment of osteoporosis and osteopenia is associated with a significantly increased risk for new-onset atrial fibrillation, as reported in the American Journal of Cardiology.
“The results of our analysis (pooled data from randomized control trials and observational studies) suggest an increased risk of developing atrial fibrillation with use of both oral and intravenous bisphosphonates, with this risk being greater with intravenous bisphosphonates,” said Abhishek Sharma, MD.
“However, as bisphosphonate therapy significantly reduces the risk of fracture and has been shown to have morbidity and mortality benefits, we recommend that the decision regarding the use of bisphosphonate therapy to be individualized,” Dr. Sharma said. “I suggest that physicians should be aware of this association, and close surveillance should be performed on patients who are on bisphosphonate therapy. Further prospective studies are needed to investigate this association and to determine whether this is a class effect or if there are differences between specific drugs.”
2008 FDA Safety Review of Bisphosphonates
In 2008, the U.S. Food and Drug Administration (FDA) reviewed data on risk of atrial fibrillation associated with bisphosphonate use from clinical trials of alendronate, ibandronate, risedronate, and zoledronic acid (19,687 bisphosphonate treated and 18,358 placebo-treated patients). The FDA concluded that the incidence of atrial fibrillation was low in most of the studies and that no significant increase in the risk of atrial fibrillation was attributed to use of bisphosphonates.
“Our recent analysis that included about five times the number of patients (n=191,231) [as the FDA review] indicated an increased risk of serious atrial fibrillation with bisphosphonate use,” Dr. Sharma said. The meta-analysis by Dr. Sharma and colleagues involved data from 9 studies (5 randomized-controlled studies and 4 observational studies), 5 of which were published after the FDA’s safety review.
Pooled data from the studies, which involved a total of 135,347 patients, showed a significantly increased risk of new-onset atrial fibrillation with intravenous (relative risk [RR], 1.40) and oral (RR, 1.22) bisphosphonates.
The authors noted that the large sample size allowed them to capture rare events such as atrial fibrillation that might go undetected in smaller studies. They also noted that the absolute risk of atrial fibrillation found in their study is relatively low (1.1% and 0.4% for intravenous and oral bisphosphonates, respectively).
The findings suggest that “perhaps it would be worthwhile for an FDA re-review, to revisit this association,” said Dr. Sharma.
A representative from the FDA told SpineUniverse that “FDA will look at the study.” The FDA had no further comment at this time.