Bisphosphonate use unrelated to risk for atrial fibrillation

The risk for atrial fibrillation and flutter may not be increased by the use of bisphosphonates, according to a recent study published in the British Medical Journal.

Researchers from Aarhus University Hospital in Denmark and other institutions in the United States conducted a population-based, case-controlled study in 13,586 patients with atrial fibrillation and flutter and 68,054 controls.

Current users of bisphosphonates included 435 cases (3.2%) and 1,958 controls (2.9%). Researchers found no difference among the cases or controls in etidronate and alendronate use. Compared with non-use, the adjusted relative risk of use was 0.95 (95% CI, 0.84 to 1.07); new users had a relative risk similar to continuous users.

The researchers conclude that they found no evidence to link the use of bisphosphonates to an increased risk for atrial fibrillation and flutter. – by Stacey L. Adams

BMJ. 2008;336:813-816.

When the data from the zoledronic acid clinical trial was published in the New England Journal of Medicine there was also a letter to the editor indicating that something similar had been noted in the alendronate clinical trials, but there was no statistically significant difference between those on alendronate and those on placebo. That created a great uproar and, subsequently, the FDA after additional correspondence and careful review said there was no good evidence to link bisphosphonates to atrial fibrillation. This new study in BMJ looked at a lot of patients and found no association, so the issue of the safety of bisphosphonates in respect to atrial fibrillation is a dead issue for now. Alendronate has been available for over 10 years now in millions of patients and if it were going to be a problem one would think it would have been recognized by now. Essentially, this paper adds to the long-term safety record of bisphosphonates.

Since this perspective was made, an article has appeared in the Archives of Internal Medicine reporting that the relative risk of atrial fibrillation in patients on alendronate was 1.8 compared to non-alendronate users and that perhaps 3% of atrial fibrillation might be related to alendronate use. The authors did comment that the benefits from fracture prevention most likely trump the possible downside from atrial fibrillation. I still think that the long-term safety record of bisphosphonates is excellent. Remember the FDA holds osteoporosis therapies to the very high standard of demonstrating that they reduce fractures, not just improve bone density.

– Michael Kleerekoper, MD, MACE

Endocrine Today Editorial Board member