Denosumab safer than romosozumab in terms of cardiovascular outcomes

Denosumab appears to have a neutral effect on the risk of composite and specific cardiovascular outcomes among patients with primary osteoporosis, whereas romosozumab may contribute to an increased risk of four-point major adverse cardiovascular event (4P MACE), according to the results of a meta-analysis.

Researchers searched multiple online databases for randomized clinical trials evaluating the effect of denosumab or romosozumab vs active comparators or placebo for at least 6 months in patients with primary osteoporosis or osteopaenia. Risk of bias was assessed in accordance with PRISMA guidelines.

The meta-analysis included 17 relevant studies, 11 of which were on denosumab (n=13,615 participants) and six were on romosozumab (n=12,219 participants). Pooled data showed no associations between denosumab therapy and risk of the following: a composite cardiovascular outcome (risk ratio [RR], 1.06, 95 percent confidence interval [CI], 0.88–1.28; p=0.54), three-point major adverse cardiovascular event (3P MACE; RR, 1.01, 95 percent CI, 0.83–1.23; p=0.93) and 4P MACE (RR, 0.99, 95 percent CI, 0.83–1.18;  p=0.89).

Romosozumab therapy, on the other hand, was associated with a heightened risk of 4P MACE (RR, 1.39, 95 percent CI, 1.01–1.90; p=0.04) among elderly men and postmenopausal woman with osteoporosis over a period of 12–36 months. Results were neutral for the risk of composite cardiovascular outcome (RR, 1.26, 95 percent CI, 0.95–1.68; p=0.11) and 3P MACE (RR, 1.41, 95 percent CI, 0.99–2.02; p=0.06).

Neither denosumab nor romosozumab exerted influence on specific cardiovascular outcomes, including cardiovascular death or any death, myocardial infarction, stroke, atrial fibrillation, heart failure, aortic and intracranial aneurysm, aortic dissection, aortic valve disease, and hypertension (p-all>0.05).

Sensitivity analysis modified the risk estimate for 4P MACE with romosozumab (RR, 1.36, 95 percent CI, 0.99–1.87; p=0.06).

Large observational studies with information on baseline cardiovascular disease risk and drug treatment and clear definitions of cardiovascular disease events are needed to fully understand the effects that denosumab or romosozumab therapies on cardiovascular disease outcomes, researchers said.