Evolocumab Improves Cardiovascular Outcomes

March 17, 2017

Evolocumab Improves Cardiovascular Outcomes

  1. Harlan M. Krumholz, MD, SM

Outcomes benefits were present, although somewhat less than anticipated, setting the stage for pricing debates and real-world monitoring of evolocumab's use.

  1. Harlan M. Krumholz, MD, SM

Prior research on evolocumab — a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) — has shown that this now FDA-approved drug can reduce LDL-cholesterol levels by 50% to 60% (NEJM JW Cardiol Jun 2014 and N Engl J Med 2014; 370:1811). We now have data from FOURIER, a manufacturer-funded outcomes trial of the drug (NCT01764633).

Researchers randomized 27,564 statin-treated patients with atherosclerotic cardiovascular disease (CVD) and LDL levels ≥70 mg/dL (median, 92 mg/dL) to receive subcutaneous evolocumab (140 mg every 2 weeks or 420 mg every month, as the patient preferred) or matching placebo. By 48 weeks of treatment, the drug had reduced LDL levels by 59%, compared with placebo, to a median of 30 mg/dL.

During a median follow-up of 2.2 years, incidence of the primary composite endpoint — cardiovascular death, myocardial infarction (MI), stroke, hospitalization for unstable angina, or coronary revascularization — was significantly lower with evolocumab than with placebo (9.8% vs. 11.3%; hazard ratio, 0.85; 95% confidence interval, 0.79–0.92), as was incidence of the main secondary endpoint of cardiovascular death, MI, or stroke (5.9% vs. 7.4%; HR, 0.80; 95% CI, 0.73–0.88). Findings were consistent across major subgroups. No prominent safety concerns emerged. There was no difference in all-cause mortality.

Comment

In this randomized trial, statin-treated patients with atherosclerotic CVD and relatively low baseline LDL levels had significant outcomes benefits with evolocumab, beyond its further LDL-lowering effects. Notably, some experts had predicted that the drug would yield even greater outcomes benefits (residual risk was still considerable). The question now is how to price the drug — and how best to communicate with patients about this treatment option. Also, as many more people start taking evolocumab (including those who do not meet FOURIER's inclusion criteria), safety and effectiveness will need to be monitored vigilantly.

Editor Disclosures at Time of Publication

  • Disclosures for Harlan M. Krumholz, MD, SM at time of publication Consultant / Advisory board United Healthcare (Advisory Board); Element Science (Consultant) Equity ImageCor; Hugo PHR Grant / Research support Agency for Healthcare Research and Quality; Food and Drug Administration; National Heart, Lung, and Blood Institute; Robert Wood Johnson Foundation; Medtronic; Johnson & Johnson; Chinese National Center for Cardiovascular Disease; Centers for Medicare & Medicaid Services Editorial boards BMJ.com/US; American Journal of Managed Care; American Journal of Medicine; Archives of Medical Science; Critical Pathways in Cardiology; Current Cardiovascular Risk Reports; JACC: Cardiovascular Imaging; Circulation: Cardiovascular Quality and Outcomes; Circulation (Associate Editor)

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