SEATTLE, Washington—A second study linking bisphosphonates to atrial fibrillation (AF) has found that alendronate (Fosamax^®) nearly doubles AF risk in women. Susan R. Heckbert, MD, PhD, from the cardiovascular health research unit at the University of Washington in Seattle, reported the study in Archives of Internal Medicine.¹

The researchers studied >700 female Group Health patients whose AF was first detected during a 3-year period. The subjects were compared in a case-control study to >900 randomly selected female Group Health members matched for age, presence or absence of treated hypertension, and calendar year.

“Having ever used alendronate was associated with an 86% higher risk of newly detected AF compared with never having used the drug,” Dr. Heckbert said. New AF rates were 6.5% with alendronate versus 4.1% with no prior bisphosphonate (P = .03). The odds ratio for developing AF was 1.86 for alendronate versus no prior bisphosphonate (95% CI 1.09-3.15). The researchers estimate that, based on the population-attributable fraction, alendronate might be responsible for 3% of the incident AF in women aged 30 to 84 years.

Black et al had previously reported from the HORIZON (Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly) trial AF rates of 1.3% with zoledronic acid versus 0.5% with placebo (P <.001).²

Translating research into practice

Experts tell Musculoskeletal Report that the Herbert paper and the HORIZON trial paper should not be viewed as tocsins to stop using either alendronate or zoledronic acid.

“For most women at high risk of fracture, alendronate’s benefit of reducing fractures will outweigh the risk of AF,” Dr. Heckbert said. However, she suggested that alternative to alendronate be considered for women at high risk of fractures who also have preexisting risk factors for AF such as heart failure, diabetes, or coronary disease.

Ethel S. Siris, MD, director of the Toni Stabile osteoporosis center at Columbia University Medical Center in New York City was similarly cautious. Dr. Siris told Musculoskeletal Report that the apparent association observed in the case-controlled study needs further study. “If I saw a patient with AF or with congestive heart failure or with bad diabetes—which are not at all the typical patients I see—I might be more cautious about using (alendronate or zoledronic acid). We need more studies that will help us sort this out because it is an important question.”

Nancy E. Lane, MD, director of the aging center at the University of California at Davis Medical Center in Sacramento was similarly cautious. Dr. Lane characterized the study as “an interesting observation that needs further investigation for causality.”

The Food and Drug Administration approved the first generic versions of alendronate in February.

References

1. Heckbert SR, Li G, Cummings SR, et al. Use of alendronate and risk of incident atrial fibrillation in women. Arch Intern Med. 2008;168:826-831.
2. Black DM, Delmas PD, Eastell R, et al. N Engl J Med. 2007;356:1809-1822.