LDL-C-lowering with evolocumab safe over long term

The long-term use of evolocumab to lower low-density lipoprotein cholesterol (LDL-C) levels appears safe, with consistently low frequency of adverse events over 8 years and leading to further reductions in cardiovascular events, according to a study.

The study involved 27,564 patients with atherosclerotic cardiovascular disease (ASCVD) and LDL-C ≥70mg/dl on statin who were enrolled in the FOURIER trial and then randomized to either evolocumab or placebo. Those who completed the trial were included in the open-label extension studies (FOURIER-OLE) in the United States and Europe.

A total of 6,635 patients received evolocumab in FOURIER-OLE, of whom 3,355 had been treated with evolocumab and 3,280 with placebo in the parent study. Median follow-up in the open-label study was 5.0 years, and the maximum exposure to evolocumab in FOURIER plus FOURIER-OLE was 8.4 years.

Twelve weeks into FOURIER-OLE, the patients had a median LDL-C of 30 mg/dl, with more than half of them (63.2 percent) achieving LDL-C <40 mg/dl on evolocumab. The frequency of serious adverse events, muscle-related events, new-onset diabetes, haemorrhagic stroke, and neurocognitive events with long-term evolocumab did not increase over time and did not exceed those observed among placebo-treated patients during the parent study.

Over the open-label follow-up period, patients who originally received evolocumab vs placebo in the parent trial had a 15-percent reduced risk of cardiovascular death, myocardial infarction (MI), stroke, hospitalization for unstable angina or coronary revascularization (hazard ratio [HR], 0.85, 95 percent confidence interval [CI], 0.75–0.96; p=0.008); a 20-percent reduced risk of cardiovascular death, MI, or stroke (HR, 0.80, 95 percent CI, 0.68–0.93; p=0.003); and a 23-percent decreased risk of cardiovascular death (HR, 0.77, 95 percent CI, 0.60–0.99; p=0.04).