Zoledronic acid modestly increases atrial fibrillation risk vs. denosumab
Adults with osteoporosis prescribed zoledronic acid have an increased risk for atrial fibrillation when compared with denosumab, according to a study data.
“While previous observational studies on this topic have struggled with confounding and yielded equivocal results, our study using an active comparator design, restriction to incident users eligible for both treatment strategies, and propensity score matching in a large cohort support findings from randomized controlled trials suggesting that zoledronic acid does increase the risk of atrial fibrillation in the first year of treatment,” Sara Jane Cromer, MD, clinical and research fellow in endocrinology at Massachusetts General Hospital, told Healio.
Cromer presented the findings at the American Society for Bone and Mineral Research virtual meeting.
Cromer and colleagues conducted an active-comparator study analyzing claims data collected from the Clinformatics Data Mart from 2010 to June 2019. Two groups were analyzed using propensity score matching. One cohort included adults with osteoporosis, the other included adults with malignancy-related bone disease. All study participants were aged at least 50 years, used zoledronic acid or denosumab (Prolia, Amgen) and had no prior history of arrhythmia or advanced kidney disease. Researchers recorded whether each participant had a diagnosis or treatment for atrial fibrillation within 1 year of starting medication, incidents of stroke or transient ischemic attack, and occurrences of nonvertebral osteoporotic fractures.
In the osteoporosis group (n = 16,235 pairs; 93% women; mean age 71 years), those taking zoledronic acid had an increased risk for atrial fibrillation when compared with those taking denosumab (HR = 1.25; 95% CI, 1.04-1.5). Differences in risk among the malignancy cohort (n = 7,732 pairs; 66% women; mean age, 70 years) were not significant.
Both the osteoporosis and malignancy cohorts showed no increased risk for stroke or transient ischemic attack with zoledronic acid. However, in the malignancy group, those treated with zoledronic acid had a higher risk for nonvertebral osteoporotic fractures than those treated with denosumab (HR = 1.32; 95% CI, 1.01-1.74). Cromer said this finding was consistent with previously conducted randomized trials comparing zoledronic acid and denosumab. There was no difference in risk for nonvertebral fractures in the osteoporosis group.
Although study data revealed an increased atrial fibrillation risk for those taking zoledronic acid in the osteoporosis group, Cromer said it should not keep providers from prescribing the treatment.
“Although clinicians should be aware of this risk with zoledronic acid, overall risk remains low, and this should not discourage use of zoledronic acid in patients who would benefit from the medication,” Cromer said. “Denosumab may be superior to zoledronic acid for prevention of skeletal-related events in patients with bone metastases.”
Cromer said providers prescribing zoledronic acid therapy must consider the risks for atrial fibrillation and closely monitor those who are undergoing treatment.
Collapse
Cromer SJ, et al. Risk of incident atrial fibrillation with zoledronic acid versus denosumab: a propensity-score matched cohort study. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 11-15, 2020 (virtual meeting).