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Title: | Cardiovascular Safety of Denosumab Across Multiple Indications: A Systematic Review and Meta-Analysis of Randomized Trials. | Authors: | Abrahamsen B.;Seeto A.H.;Ebeling P.R. ;Rodriguez A.J. | Institution: | (Seeto) School of Medicine, Griffith University, Gold Coast, Australia (Abrahamsen, Rodriguez) OPEN-Odense Patient Data Explorative Network, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark (Abrahamsen) Musculoskeletal Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (Abrahamsen) Department of Medicine, HolbaekHospital, Holbaek, Denmark (Ebeling, Rodriguez) Bone and Muscle Health Research Group, Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Monash Medical Centre, Clayton, Australia (Ebeling) Australian Institute for Musculoskeletal Science, St Albans, Australia (Rodriguez) Disorders of Mineralisation Research Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia | Issue Date: | 9-Mar-2021 | Copyright year: | 2021 | Publisher: | John Wiley and Sons Inc | Place of publication: | United States | Publication information: | Journal of Bone and Mineral Research. 36 (1) (pp 24-40), 2021. Date of Publication: January 2021. | Journal: | Journal of Bone and Mineral Research | Abstract: | The cardiovascular safety of denosumab has not yet been evaluated in a systematic review. This systematic review and meta-analysis sought to quantify the number of randomized controlled trials (RCTs) of denosumab (against comparators) reporting cardiovascular adverse events (CAEs) and examine the balance of CAEs between treatment arms. MEDLINE, Embase, and clinicaltrials.gov were searched from inception to October 26, 2019, for RCTs of denosumab versus comparators for any indication. Included trials were randomized, enrolled >=100 participants, and reported bone-related outcomes. Primary outcome for analysis was all CAEs, a composite endpoint representing summation of all CAEs as reported by included trials. Secondary outcomes included major adverse cardiovascular events (MACE). Data were pooled using a fixed effects model to determine relative risk (RR) and 95% confidence interval (95% CI). Risk of bias was assessed using the Cochrane risk-of-bias tool. Of 554 records screened, 49 were included, while 36 reported CAEs. Twenty-seven included trials (12 eligible for meta-analysis) were conducted in 13,202 postmenopausal women. Compared with bisphosphonates, there was a 46% (95% CI 1.05 to 2.02) increase in CAEs (85/2136 events in denosumab-treated versus 58/2131 events in bisphosphonate-treated; seven trials). There was a similar imbalance in a five-point (stroke, myocardial infarction, cardiovascular death, heart failure, atrial fibrillation) MACE endpoint (28/2053 versus 12/2050; RR = 2.33 [1.19 to 4.56]). Compared with placebo-treated women, there was no imbalance in total CAEs (439/4725 events in denosumab versus 399/4467 in placebo; RR = 0.79 [0.41 to 1.52]; seven trials). No imbalance in total AEs (versus bisphosphonates: 0.98 [0.92 to 1.04]; versus placebo: 0.99 [0.98 to 1.01]) occurred. Other indications showed no statistically significant results. The excess CAEs in postmenopausal women treated with denosumab compared with bisphosphonates, but not placebo, indirectly supports claims that bisphosphonates may suppress CAEs. Future trials should use standardized CAE reporting to better describe cardiovascular effects of bone active medications. (PROSPERO: CRD42019135414.) © 2020 American Society for Bone and Mineral Research (ASBMR). | DOI: | http://monash.idm.oclc.org/login?url= http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1002/jbmr.4157 |
PubMed URL: | 32780899 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32780899] | ISSN: | 0884-0431 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/27053 | Type: | Article | Subjects: | coronary artery disease/si [Side Effect] *drug indication *drug safety female heart failure/si [Side Effect] heart infarction/si [Side Effect] human hypertension/si [Side Effect] male meta analysis multiple myeloma/dt [Drug Therapy] osteoclast osteolysis osteoporosis/dt [Drug Therapy] peripheral vascular disease/si [Side Effect] postmenopause postmenopause osteoporosis/dt [Drug Therapy] prostate cancer/dt [Drug Therapy] randomized controlled trial (topic) risk factor side effect/si [Side Effect] systematic review vitamin supplementation alendronic acid/ae [Adverse Drug Reaction] alendronic acid/cm [Drug Comparison] alendronic acid/dt [Drug Therapy] bisphosphonic acid derivative/ae [Adverse Drug Reaction] bisphosphonic acid derivative/cm [Drug Comparison] calcium *denosumab/ae [Adverse Drug Reaction] *denosumab/cm [Drug Comparison] *denosumab/dt [Drug Therapy] glucocorticoid minodronic acid/ae [Adverse Drug Reaction] minodronic acid/cm [Drug Comparison] minodronic acid/dt [Drug Therapy] risedronic acid/ae [Adverse Drug Reaction] risedronic acid/cm [Drug Comparison] risedronic acid/dt [Drug Therapy] vitamin D zoledronic acid/ae [Adverse Drug Reaction] zoledronic acid/cm [Drug Comparison] zoledronic acid/dt [Drug Therapy] rheumatoid arthritis/dt [Drug Therapy] acute coronary syndrome/si [Side Effect] acute heart failure/si [Side Effect] acute heart infarction/si [Side Effect] article atrial fibrillation/si [Side Effect] bone density bone metastasis/dt [Drug Therapy] brain hemorrhage/si [Side Effect] brain ischemia/si [Side Effect] breast cancer/dt [Drug Therapy] *cardiovascular disease/si [Side Effect] *cardiovascular effect cardiovascular mortality cerebrovascular accident/si [Side Effect] clinical outcome congestive heart failure/si [Side Effect] cardiovascular mortality cerebrovascular accident / side effect clinical outcome congestive heart failure / side effect coronary artery disease / side effect *drug indication *drug safety female heart failure / side effect heart infarction / side effect human hypertension / side effect male meta analysis multiple myeloma / drug therapy osteoclast osteolysis osteoporosis / drug therapy peripheral vascular disease / side effect postmenopause postmenopause osteoporosis / drug therapy prostate cancer / drug therapy randomized controlled trial (topic) acute heart infarction / side effect risk factor side effect / side effect systematic review vitamin supplementation acute heart failure / side effect acute coronary syndrome / side effect rheumatoid arthritis / drug therapy Article atrial fibrillation / side effect bone density bone metastasis / drug therapy brain hemorrhage / side effect brain ischemia / side effect breast cancer / drug therapy *cardiovascular disease / *side effect *cardiovascular effect |
Type of Clinical Study or Trial: | Systematic review and/or meta-analysis |
Appears in Collections: | Articles |
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