Cardiovascular adverse events associated with denosumab versus zoledronic acid in patients with breast cancer: a propensity score overlap weighted analysis.

BACKGROUND: To compare the risks of cardiovascular events, fractures, and all-cause mortality between denosumab and zoledronic acid in patients with breast cancer bone metastases. PATIENTS AND METHODS: We identified female patients with breast cancer and bone metastases who received denosumab or zoledronic acid between April 2014 and August 2023 from a nationwide database of routinely collected administrative claims data in Japan. After adjusting for potential confounders using propensity score overlap weighting, we estimated the incidence of outcomes (per 10,000 person-years) and hazard ratios (HRs) using Cox proportional hazards models. RESULTS: Among the eligible 4350 patients, 2953 received denosumab and 1397 received zoledronic acid. The participants' median age was 76 years (interquartile range, 68 to 81). The adjusted incidence of composite cardiovascular disease was 118 in the denosumab group and 152 in the zoledronic acid group (HR 0.80, 95% confidence interval, 0.67 to 0.95). Heart failure was less frequent in patients administered denosumab [65 vs. 92; HR, 0.69 (0.55 to 0.87)] than in those administered zoledronic acid, whereas the rates of stroke and myocardial infarction were similar between the two groups. Denosumab was also associated with lower risks of any fracture [237 vs. 298; HR 0.80 (0.71 to 0.90)], hip (31 vs. 43), vertebral (135 vs. 168), and non-vertebral (114 vs. 142) fractures. Overall, 471 all-cause mortality events occurred in the denosumab group and 610 in the zoledronic acid group [HR 0.75 (0.69 to 0.82)]. CONCLUSION: In patients with breast cancer bone metastases, denosumab was associated with lower risks of cardiovascular events, fractures, and mortality than those with zoledronic acid.