Osteoporosis treatment linked to adverse cardiovascular events

Evenity, a monoclonal antibody that inhibits sclerostin used to treat osteoporosis, may increase patients’ risk for adverse cardiovascular events, according to research published in Science Translational Medicine.

“Our findings support the U.S. FDA and EMA’s addition of a warning for cardiovascular risk to [the Evenity (romosozumab, Amgen)] label and indicate that other therapies inhibiting sclerostin are also likely to exert similar cardiovascular effects,” Jonas Bovijn, MBChB, MSc, DLSHTM, of the Big Data Institute at the University of Oxford’s Li Ka Shing Centre for Health Information and Discovery, and colleagues wrote.

Bovijn and colleagues conducted a meta-analysis of published and unpublished data on cardiovascular outcomes in trials of romosozumab and investigated whether genetic variants that mimic the therapeutic inhibition of sclerostin are linked to an increased risk for CVD.

They found that results from two phase 3 randomized controlled trials with 25 events among 4,298 participants showed that taking 210 mg per month of romosozumab was associated with an increased risk for cardiac ischemic events (OR = 2.98; 95% CI, 1.18-7.55).

When researchers scaled SOST genetic variants to the equivalent dose of romosozumab, they were associated with reduced risks for fracture and developing osteoporosis. However, they also determined that these variants were associated with an 18% increased risk for myocardial infarction and/or coronary revascularization (69,649 cases; OR = 1.18; 95% CI, 1.06-1.32) and a 12% increased risk for major adverse cardiovascular events (119,032 cases; OR = 1.12; 95% CI, 1.03-1.21).

When the researchers broadened their definition of coronary heart disease to include self-reported angina and chronic stable ischemic heart disease, these variants were associated with a 10% increase in risk for heart disease (106,329 cases; OR = 1.1; 95% CI, 1-1.2).

“Our results warrant a rigorous assessment of the effect of romosozumab (and other sclerostin inhibitors in clinical development) on cardiovascular disease and cardiometabolic risk factors,” Bovijn and colleagues wrote. “This adds valuable information to whether pharmacological inhibition of sclerostin should be pursued as a therapeutic strategy for the prevention of fracture.”