Risk of Cardiovascular Events in Patients with Osteoporosis on Romosozumab Treatment Compared with Denosumab: A Multicenter Observational Cohort Study.

BACKGRUOUND: Romosozumab, a potent anabolic agent for osteoporosis, has been associated with an increased risk of adjudicated cardiovascular events compared with alendronate in postmenopausal women, although such an association was not observed in a placebo-controlled trial. Evidence from real-world clinical practice remains limited.

METHODS

In this multicenter observational study, we analyzed patients aged ≥50 years who were newly prescribed romosozumab 120 mg monthly or denosumab 60 mg every 6 months for osteoporosis at three tertiary hospitals in South Korea between January 1, 2020, and the end of each site's data collection period. The primary outcomes were major adverse cardiovascular events (MACE; acute myocardial infarction, ischemic stroke, or sudden cardiac death) and all cardiovascular adverse events (CVAEs; MACE, heart failure, peripheral artery disease, and non-coronary revascularization), assessed at 1- and 3-year follow-up. Large-scale 1:1 propensity score matching and Cox proportional hazards models were applied within a common data model framework with individual-level meta-analysis.

RESULTS

A total of 4,896 patients were included in the MACE analysis (4,758 in the CVAE analysis). At 1 year, the incidence rate of MACE did not differ significantly between the romosozumab and denosumab groups (9.20 per 1,000 person-years vs. 6.43 per 1,000 person-years; adjusted hazard ratio [aHR], 1.42; 95% confidence interval [CI], 0.64 to 3.19). The risk of CVAE was also similar between groups (16.23 per 1,000 person-years vs. 15.45 per 1,000 person-years; aHR, 1.05; 95% CI, 0.62 to 1.78). At 3 years, no significant differences were observed for MACE (aHR, 1.51; 95% CI, 0.79 to 2.88) or CVAE (aHR, 1.04; 95% CI, 0.69 to 1.58).

CONCLUSION

In real-world clinical practice, romosozumab use was not associated with a statistically significant increase in cardiovascular risk compared with denosumab.