Cardiovascular Safety of Denosumab Across Multiple Indications:A Systematic Review and Meta-Analysis of Randomized Trials
| Autor: | Alexander J. Rodríguez, Peter R. Ebeling, Alexander H Seeto, Bo Abrahamsen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty MENOPAUSE Endocrinology Diabetes and Metabolism Myocardial Infarction 030209 endocrinology & metabolism Placebo OSTEOPOROSIS law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Internal medicine medicine Humans Orthopedics and Sports Medicine Adverse effect Randomized Controlled Trials as Topic Bone Density Conservation Agents Diphosphonates business.industry ANTIRESORPTIVES CANCER Clinical trial 030104 developmental biology Denosumab Meta-analysis Relative risk Female business Mace CLINICAL TRIALS medicine.drug |
| Zdroj: | Seeto, A H, Abrahamsen, B, Ebeling, P R & Rodríguez, A J 2021, ' Cardiovascular Safety of Denosumab Across Multiple Indications : A Systematic Review and Meta-Analysis of Randomized Trials ', Journal of Bone and Mineral Research, vol. 36, no. 1, pp. 24-40 . https://doi.org/10.1002/jbmr.4157 |
| DOI: | 10.1002/jbmr.4157 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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