Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease.
Level 2 - randomized trial
Individual large randomized controlled trial
PubMed 28304224 · doi:10.1056/NEJMoa1615664
What was done
A randomized, double-blind, placebo-controlled trial (FOURIER) evaluated 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL (1.8 mmol/L) or higher while on statin therapy. Participants were randomly assigned to receive subcutaneous evolocumab (140 mg every 2 weeks or 420 mg monthly) or matching placebo. The primary composite end point included cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Median follow-up was 2.2 years.
What was found
At 48 weeks, evolocumab reduced LDL cholesterol by a least-squares mean of 59% compared to placebo, from a median baseline of 92 mg/dL to 30 mg/dL (P < 0.001). Evolocumab significantly reduced the primary composite end point (9.8% [1,344 patients] vs. 11.3% [1,563 patients]; HR 0.85; 95% CI, 0.79 to 0.92; P < 0.001) and the key secondary end point of cardiovascular death, myocardial infarction, or stroke (5.9% [816 patients] vs. 7.4% [1,013 patients]; HR 0.80; 95% CI, 0.73 to 0.88; P < 0.001). Overall adverse events, including new-onset diabetes and neurocognitive events, did not differ significantly between groups, though injection-site reactions were higher with evolocumab (2.1% vs. 1.6%).
Why it matters
This trial established that lowering LDL cholesterol well below conventional targets using a PCSK9 inhibitor provides additional cardiovascular risk reduction in established atherosclerotic disease.
Limits
The median follow-up of 2.2 years is relatively short for assessing long-term safety and overall survival effects. The abstract does not break down individual mortality components, and the trial only included high-risk patients already receiving background statin therapy.
Cited by
- supports The monoclonal antibody Repatha (evolocumab) blocks the PCSK9 protein in the liver and reduces LDL cholesterol levels by half.