Study finds link between alendronate use and risk for atrial fibrillation

Women who have ever used alendronate sodium may be at an increased risk of incident atrial fibrillation, according to recent data published in the Archives of Internal Medicine.

Researchers from Washington and California conducted a population-based case control study of 719 women with incident atrial fibrillation and 966 randomly selected controls.

Compared with controls, more atrial fibrillation patients had ever used alendronate: 4.1% vs. 6.5% (P=.03), according to the researchers. Ever use of alendronate was also linked to a higher risk of incident atrial fibrillation, compared with those who had never used a bisphosphonate (OR=1.86; 95% CI, 1.09-3.15).

The researchers estimated that alendronate use may explain 3% of incident atrial fibrillation in the study population. – by Stacey L. Adams

Arch Intern Med. 2008;168:826-831.

The issue of atrial fibrillation after use with the family of drugs called bisphosphonates, was raised initially by a big study with zoledronic acid in osteoporosis where serious episodes of atrial fibrillation appeared to occur slightly more frequently, or statistically more significantly in the treated group vs. placebo. However, this paper fails to point out a second study published in the New England Journal of Medicine by Lyles et al. They studied hip fracture patients, roughly 1,000 treated vs. 1,000 placebo, and there was no difference in atrial fibrillation. In this case-controlled study it looks like there is a 3% risk, but then in an actual randomized, double-blind study, the hip fracture study, there was no difference. There is a risk of case-controlled studies not necessarily being the whole truth, which this study points out. There are two problems. First, there is no consistent evidence that atrial fibrillation is caused by a bisphosphonate. It is possible, but there is no absolute evidence. Second, the mechanism is unclear, particularly because in the intravenous studies, the problem developed at least 30 days after a single infusion. It is a little hard to blame the drug when it occurred so long after the drug had vanished from the blood.

The message is that doctors and patients should be aware that there is a question of atrial fibrillation after or during bisphosphonate therapy. It is a very small risk, and it is not absolutely proven that the drug causes atrial fibrillation. The benefits of these drugs appear to outweigh the risk of developing atrial fibrillation.

– Frederick Singer, MD

Director, Endocrine/Bone Disease Program
John Wayne Cancer Institute, Saint John’s Health Center, Santa Monica, Calif.