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Risk of Incident Atrial Fibrillation With Zoledronic Acid Versus Denosumab: A Propensity Score–Matched Cohort Study

Zoledronic acid (ZA) is an effective agent in osteoporosis and malignancy‐related bone disease but may be associated with increased risk of atrial fibrillation (AF), although current studies disagree on this risk. To examine the risk of incident AF among patients receiving ZA compared with denosumab in the first year of treatment, we performed a new‐user, active comparator cohort study including privately insured Americans between January 1, 2010, and June 30, 2019. Individuals aged ≥50 years without known arrhythmia or advanced kidney disease who initiated ZA were 1:1 propensity score (PS)‐matched to individuals initiating denosumab in separate osteoporosis and malignancy cohorts. The primary outcome was incident diagnosis of AF (≥1 inpatient or ≥2 outpatient diagnostic codes) over 1 year. Secondary outcomes included stroke/transient ischemic attack (TIA) and nonvertebral fracture. In the osteoporosis cohort (n = 16,235 pairs), mean age was 71 years, and 93% were female. There was higher risk of AF with ZA compared with denosumab over 1 year (incidence rate [IR] = 18.6 versus 14.9 per 1000 person‐years; hazard ratio [HR] = 1.25; 95% confidence interval [CI] 1.04 to 1.50). In the malignancy cohort (n = 7732 pairs), mean age was 70 years, and 66% were female. There was a numerically higher, albeit not statistically significant, risk of AF with ZA compared with denosumab over 1 year (IR = 46.9 versus 39.0 per 1000 person‐years; HR = 1.19; 95% CI 1.00 to 1.43; p = 0.06). No difference in stroke/TIA rates occurred. In the malignancy cohort, ZA was less effective than denosumab at preventing nonvertebral fractures (HR = 1.32; 95% CI 1.01 to 1.74). Compared with denosumab, ZA treatment for osteoporosis and possibly for malignancy‐related bone disease is associated with modestly increased risk of incident AF in the first year of treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).