(L) Comparative Cardiovascular Events Associated with Denosumab Vs. Zoledronate in The Elderly: A 5-Year Follow-Up Propensity Score Matching Cohort

Publication Number: 302

Background: Osteoporosis and atherosclerosis share similar risk factors and pathological mechanisms in developing cardiovascular events. Two long-acting injections, denosumab and zoledronate, are commonly used for osteoporosis treatment due to better persistence in therapy, but comparisons of long-term cardiovascular events between these two drugs remain unclear, especially in the elderly Asian population.

Objectives: To compare the cardiovascular event risk between denosumab and zoledronate in patients with osteoporosis.

Methods: We conducted a retrospective cohort study analyzing the largest multi-institutional electronic medical records database in Taiwan covering 1.3 million individuals or 6% of the Taiwan population. We included osteoporotic patients aged over 65 years without cardiovascular events at baseline, newly receiving denosumab or zoledronate during 2015-2016, and used 1:1 propensity score matching to ensure balanced characteristics between the two groups. The primary study outcome was the composite of cardiovascular events, including cardiovascular death, myocardial infarction, ischemic stroke and heart failure. We followed these patients until the occurrence of cardiovascular events, last clinical visit or the end of the database (31 December, 2021), and performed Cox proportion hazard model to compare the cardiovascular event risks between denosumab and zoledronate.

Results: We included a total of 3,908 denosumab and 803 zoledronate new users with mean age of 75.7 (SD 9.4) years, of whom 19.8% were men. After matching, the baseline characteristics, including sex, age, comorbidities and concomitant medications, were balanced between denosumab and zoledronate new users. After a median follow-up of 5.7 years, we identified 77 and 81 cardiovascular events in patients with denosumab and zoledronate, respectively. The incidence rate of cardiovascular events was similar between denosumab and zoledronate (17.4 vs. 18.2 per 1,000 patient-years) which yielded the hazard ratio of 0.95 (95% CI: 0.69 – 1.30).

Conclusions: Denosumab and zoledronate had similar risk of cardiovascular events in the Asian elderly with osteoporosis. Further large-scale studies are suggested to confirm our findings.