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Arch Intern Med. 2008;168(8):826-831.

Background  A recent publication from the HORIZON (Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly) trial in women with postmenopausal osteoporosis reported a higher risk of serious atrial fibrillation (AF) in zoledronic acid recipients than in placebo recipients. This adverse effect was unexpected and had not been recognized previously.

Methods  We studied alendronate sodium ever use in relation to the risk of incident AF in women in a clinical practice setting. This population-based case-control study was conducted at Group Health, an integrated health care delivery system in Washington State. We identified 719 women with confirmed incident AF between October 1, 2001, and December 31, 2004, and 966 female control subjects without AF, selected at random from the Group Health enrollment and frequency matched on age, presence or absence of treated hypertension, and calendar year.

Results  More AF case patients than controls had ever used alendronate (6.5% [n = 47] vs 4.1% [n = 40]; P = .03). Compared with never use of any bisphosphonate, ever use of alendronate was associated with a higher risk of incident AF (odds ratio, 1.86; 95% confidence interval, 1.09-3.15) after adjustment for the matching variables, a diagnosis of osteoporosis, and a history of cardiovascular disease. Based on the population-attributable fraction, we estimated that 3% of incident AF in this population might be explained by alendronate use.

Conclusion  Ever use of alendronate was associated with an increased risk of incident AF in clinical practice.

Author Affiliations: Cardiovascular Health Research Unit (Drs Heckbert, Smith, and Psaty and Mr Li) and Departments of Epidemiology (Drs Heckbert, Smith, and Psaty) and Medicine (Mr Li and Dr Psaty), University of Washington, Seattle; Center for Health Studies, Group Health, Seattle (Drs Heckbert and Psaty); San Francisco Coordinating Center, California Pacific Medical Center Research Institute and University of California, San Francisco (Dr Cummings); and Seattle Epidemiologic Research and Information Center, Veterans Administration Puget Sound Health Care System, Seattle (Dr Smith).

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