Evolocumab’s Effect on Total Cardiovascular Events

Evolocumab was associated with a reduction in total cardiovascular burden, according to an analysis of the FOURIER trial.

The paper, published in JAMA Cardiology, was a deeper analysis of the results form the FOURIER study, presented in 2018. In the FOURIER study, evolocumab, a PCSK9 inhibitor that was shown to reduce low-density lipoprotein cholesterol (LDL-C) and first cardiovascular events in high-risk patients who were taking statins. The present secondary analysis focused on how evolocumab affected the total number of cardiovascular events in the FOURIER patient population. The analysis included a look at the data on the 27,564 patients in FOURIER, who all had stable atherosclerotic disease. The primary analysis endpoint was the time to first cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The researchers set the key secondary endpoint as time to first cardiovascular death, myocardial infarction, or stroke.

Total cardiovascular events between treatment arms were evaluated in a per-specified analysis. Mean patient age was 63 years, and just under 70% of the patients were taking high-intensity statin therapy. Media LDL-C at baseline was 92 mg/dL.

Evolocumab Effective

According to the study results, there were 2,907 first primary endpoint events and 4,906 total primary endpoint events during the study. Evolocumab was associated with an 18% decrease in total primary endpoint events (incidence rate ratio [RR]=0.82; 95% CI, 0.75 to 0.90; P<0.001), including first events (HR=0.85; 95% CI, 0.79 to 0.92; P<0.001) and subsequent events (RR=0.74; 95% CI, 0.65 to 0.87). According to the authors, evolocumab prevented 22 first primary endpoint events and 52 total primary endpoint events for every 1,000 patients treated for three years (P<0.001). This risk reduction was driven by reductions in strokes (P=0.007) and coronary revascularizations (P<0.001).

“The addition of the PCSK9 inhibitor evolocumab to statin therapy improved clinical outcomes, with significant reductions in total primary endpoint events, driven by decreases in myocardial infarction, stroke, and coronary revascularization,” the authors wrote in their conclusion. “More than double the number of events were prevented with evolocumab versus placebo as compared with the analysis of only first events. These data provide further support for the benefit of continuing aggressive lipid-lowering therapy to prevent recurrent cardiovascular events.”