Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events (OSLER)

The OSLER (Open-label Study of Long-term Evaluation Against LDL Cholesterol) trials enrolled 4,465 patients who had completed prior evolocumab phase 2 and 3 studies and randomized them to evolocumab plus standard care versus standard care alone, following them for 1 year to assess long-term safety and cardiovascular event rates.

Evolocumab reduced LDL-C by 61% from baseline and maintained LDL-C of approximately 48 mg/dL over the follow-up period. Adverse events were similar between groups. In an exploratory, non-prespecified event analysis, the evolocumab group had a significantly lower rate of major adverse cardiovascular events (0.95% vs. 2.18% annualized, HR 0.47, p=0.003).

OSLER was not powered or designed as a cardiovascular outcomes trial — it was an open-label long-term safety extension. The cardiovascular signal was exploratory, with a small event count and open-label design introducing possible bias. However, as precursor data to the definitive FOURIER trial, the OSLER cardiovascular trend was hypothesis-generating and consistent with the subsequently confirmed FOURIER result.

OSLER established that long-term evolocumab (12 months) is safe, produces sustained LDL-C reduction, and generated the early cardiovascular efficacy signal that motivated the FOURIER trial design and enrollment.

We rate the evidence moderate. An open-label long-term safety trial with an exploratory cardiovascular endpoint — important precursor data to FOURIER but not itself definitive evidence for event reduction.