Oral Presentation 29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019

Cardiovascular safety of denosumab versus bisphosphonates or placebo in post-menopausal women: systematic review and meta-analysis (#40)

Alexander H. Seeto 1 , Bo Abrahamsen 2 , Daniel Prieto-Alhambra 3 , Peter R. Ebeling 4 , Alexander J. Rodriguez 4
  1. School of Medicine, Griffith University, Southport, QLD, Australia
  2. OPEN-Odense Patient Data Explorative Network, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
  3. Musculoskeletal Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
  4. Bone and Muscle Health Research Group, Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia

Introduction: Increasing evidence suggests that bisphosphonates may be cardioprotective. Randomised controlled trials (RCTs) have shown denosumab to have a similar overall safety profile to bisphosphonates. However, no study has comprehensively evaluated the cardiovascular safety of denosumab. Therefore, we conducted a systematic review to compare cardiovascular events (CAEs) in post-menopausal women treated with denosumab, bisphosphonates or placebo.

Methods: We searched MEDLINE, EMBASE and clinicaltrials.gov from inception to May 2019 for RCTs comprising >100 participants, which compared denosumab with any comparator and reported on skeletal outcomes. We extracted CAE data from all eligible trials, where a composite outcome was created, summating all reported CAEs. Summary effect estimates (relative risk (RR) and 95% confidence interval (CI)) were calculated using fixed effects models.

Results: We identified 27 trials. Most trials (n=23/27) administered 60mg subcutaneous denosumab injections (six monthly). Follow-up ranged from 6-36 months. Ten trials compared denosumab with bisphosphonates (alendronate n=6, risedronate n=1, ibandronate n=1, zoledronic acid n=1, combination n=1); 17 trials were placebo-controlled. Fifteen trials had data for meta-analysis. Of these, 13 were published and two had data available through clinicaltrials.gov. There were 124 CAEs in 2300 women randomised to denosumab compared with 89 CAEs in 2293 women randomised to any bisphosphonate [RR=1.39 (95%CI: 1.07 to 1.81)]. There was no significant increase in risk compared with placebo [n=736/5931 events in denosumab vs n=715/5597 events in placebo; RR=0.98 (0.90 to 1.06)]. There was no imbalance in total AEs [versus bisphosphonates: RR=0.98 (0.95 to 1.02); versus placebo: RR=0.99 (0.98 to 1.01)].

Conclusion: There appeared to be a greater number of CAEs experienced by post-menopausal women treated with denosumab compared with bisphosphonates, but no imbalance compared with placebo. Studies were limited by poor reporting of specific CAEs. Our data are consistent with prior reports of lower CAEs in bisphosphonate-treated individuals in both RCTs and observational studies.5d142ecad0a70-CONFERENCE+PICTURE.tif