Use of Alendronate and Risk of Incident Atrial Fibrillation in Women

Abstract

ABSTRACT Recent trials have suggested an increased risk of serious atrial fibrillation (AF) in osteoporotic women taking alendronate or zoledronic acid—an unanticipated side-effect that had not been recognized previously. The present trial is an ongoing population-based case-control study of risk factors for incident AF taking place in a clinical practice setting. The case group of 719 women confirmed as having AF in the years 2001–2004 was compared with 966 women without AF who were matched with case women for age, calendar year, and the presence or absence of treated hypertension. More case patients than control women had used alendronate at some time (6.5% versus 4.1%). The odds ratio (OR) for AF in women taking alendronate at any time, compared to those never taking any bisphosphonate drug, was 1.86, with a 95% confidence interval (CI) of 1.09–3.15 after adjusting for the matching variables, a diagnosis of osteoporosis, and a history of cardiovascular disease. Further adjustment for numerous possible confounding factors yielded an OR of 1.83 (95% CI, 1.04–3.24). The OR was slightly but not significantly higher for past users than for current users. Neither the total cumulative dose of alendronate dispensed nor the time since first use significantly influenced the risk of AF. AF was transient in approximately 42% of cases, intermittent or persistent in 46%, and sustained in 11.5%. Based on the population-attributable fraction, it was estimated that 3% of incident cases of AF in this population might be explained by the use of alendronate. The risk of AF associated with alendronate therapy was higher in diabetic patients and in those currently taking statins. These findings demonstrate the need to weigh the benefits of alendronate therapy against the possibly increased risk of AF in 2 groups of women: those with no more than a modest increase in risk of fracture, and those having risk factors for AF such as coronary disease, heart failure, or diabetes.