(065) Bisphosphonates versus Denosumab: Assessing the Risk of Heart Failure in a Nationwide Retrospective Cohort Study in Taiwan

Background: Bisphosphonates, a class of drugs widely used to treat osteoporosis, have shown both protective and adverse cardiovascular effects in various studies, leading to an inconclusive impact on heart health. Similarly, denosumab, another prevalent anti-osteoporotic medication, has demonstrated potential systemic effects beyond bone metabolism, including effects on the cardiovascular system. Given the widespread use of these anti-osteoporotic agents among the elderly, who are at high risk for heart failure (HF), understanding the differential HF risk between bisphosphonate and denosumab users is clinically relevant. However, research evidence on this issue remains scarce.

Objectives: This study aimed to compare the risk of HF development between patients treated with bisphosphonates and those treated with denosumab.

Methods: We conducted a nationwide population-based cohort study utilizing Taiwan’s National Health Insurance Research Database. Patients diagnosed with osteoporosis or osteoporotic fractures and treated with either bisphosphonates or denosumab between 2012 and 2020 in the Taiwanese population were included. Patients were categorized into bisphosphonate and denosumab groups based on their initial anti-osteoporotic treatment. The primary outcome was newly diagnosed HF. Inverse probability of treatment weighting was used to balance baseline characteristics and control potential confounders, including age, sex, income, comorbidities, medications, medical utilization, and features of healthcare providers. Cox proportional hazards models estimated the hazard ratios (HRs) for HF development.

Results: The cohort study included 97,688 patients treated with bisphosphonates and 61,404 patients treated with denosumab. Bisphosphonate use was significantly associated with a lower risk of HF compared to denosumab use (HR=0.93, 95% CI: 0.89-0.97, p< 0.001). Subgroup analyses demonstrated a consistently lower HF risk in bisphosphonate users across both sexes. However, a significant association of lower HF risk with bisphosphonate use compared to denosumab was only observed in patients aged ≥ 65 years (HR=0.93, 95% CI: 0.90-0.97, p=0.001), not in those < 65 years. Sensitivity analyses, such as applying competing risk models to address the competing event of mortality and conducting analyses of negative control outcomes, further supported our findings.

Conclusions: Compared to denosumab, bisphosphonate use was associated with a lower risk of HF development in patients treated for osteoporosis. Although the effects appear subtle, the high prevalence and incidence of osteoporosis and HF make our study of clinical importance. Further research is needed to confirm our findings.