Atrial fibrillation and the use of oral bisphosphonates

Background: Epidemiological studies investigating a possible association between bisphosphonates and atrial fibrillation (AF) have reported conflicting findings. The objective of our study was to determine whether exposure to oral nitrogen-containing bisphosphonates alendronate and risedronate are associated with increased incidence of atrial fibrillation. Methods: In a retrospective cohort study we analyzed data from three large independent databases, two from the United States (MarketScan (R) and Ingenix (R)) and one from the United Kingdom (THIN). 144,548 women, age 50-89, bisphosphonate users during 2002-2005 were compared to 668,891 sex- and age-matched controls (1:4). Our primary outcome measure was new incident atrial fibrillation for up to three years; Cox models adjusted for disease and drug history were used to estimated relative risks. Results: We identified a total of 8,001, 1,984, and 817 AF cases in oral bisphosphonate users and nonusers during 744,340 (MarketScan), 243,898 (Ingenix), and 148,779 (THIN) person-years of follow-up, respectively. Compared to nonusers, overall adjusted relative risk (adjRR) (95% confidence interval [CI]) for AF in oral bisphosphonates users was 0.92 (0.85-0.99; MarketScan), 1.00 (0.87-1.16; Ingenix), and 0.97 (0.79-1.20; THIN); overall adjRR (95% CI) for any cardiac dysrrhythmia for MarketScan was 1.01 (0.98-1.05), Ingenix 1.06 (0.99-1.13), and THIN 0.97 (0.79-1.20). Conclusions: In all three databases from the two countries, the risk of AF or cardiac dysrrhythmia was not increased in postmenopausal women treated for up to three years with oral alendronate or risedronate.