Efficacy and Safety of Evolocumab in Primary Prevention: Insights from Recent Trials

In a pivotal trial, evolocumab reduced the risk of a first major cardiovascular event by 25% (three‑point MACE) in high‑risk adults without prior myocardial infarction or stroke.

The trial enrolled 12,257 adults with atherosclerosis or high‑risk diabetes and no prior heart attack or stroke; roughly half were randomized to evolocumab and half to placebo and were followed for a median of 4.6 years.

Three‑point MACE occurred in 336 versus 443 patients, with 5‑year Kaplan‑Meier estimates of 6.2% versus 8.0% (hazard ratio 0.75; 95% CI 0.65–0.86; P<0.001). A four‑point MACE analysis showed event rates of 13.4% versus 16.2% (HR 0.81; 95% CI 0.73–0.89), and myocardial infarction alone favored evolocumab (HR 0.64; 95% CI 0.52–0.79). LDL was reduced by about 55% at 48 weeks, with a median on‑treatment LDL near 45 mg/dL.

Safety over the median 4.6‑year follow‑up appeared broadly comparable between groups: rates of serious adverse events, treatment discontinuations, and adjudicated safety endpoints showed no new safety signals and no excess major harms attributable to the PCSK9 inhibitor. LDL lowering remained durable through follow‑up, and subgroup analyses reported consistent efficacy without a detectable safety trade‑off across prespecified strata.

Overall, the reported safety profile supports evolocumab use in the studied high‑risk, event‑free primary prevention population while acknowledging the trial's enrollment boundaries.