Evolocumab in Patients without a Previous Myocardial Infarction or Stroke

Area of Science:

• Cardiovascular Medicine
• Pharmacology

Background:

• Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, like evolocumab, are known to reduce major adverse cardiovascular events (MACE) in patients with established cardiovascular disease.
• The impact of evolocumab on MACE risk in patients without a history of myocardial infarction or stroke was previously unestablished.

Purpose of the Study:

• To evaluate the efficacy of evolocumab in reducing cardiovascular events in patients with atherosclerosis or diabetes but no prior myocardial infarction or stroke.
• To assess the safety profile of evolocumab in this patient population.

Main Methods:

• An international, double-blind, randomized, placebo-controlled trial involving 12,257 patients with atherosclerosis or diabetes and low-density lipoprotein cholesterol ≥90 mg/dL.
• Patients received either evolocumab (140 mg every 2 weeks) or placebo in a 1:1 ratio.
• Primary endpoints included a composite of coronary heart disease death, myocardial infarction, or ischemic stroke (3-point MACE) and a composite including these plus ischemia-driven revascularization (4-point MACE).

Main Results:

• Evolocumab significantly reduced the risk of 3-point MACE by 25% (HR, 0.75; P<0.001) and 4-point MACE by 19% (HR, 0.81; P<0.001) compared to placebo over a median follow-up of 4.6 years.
• The 5-year Kaplan-Meier estimate for 3-point MACE was 6.2% with evolocumab versus 8.0% with placebo.
• No significant differences in safety event incidence were observed between the evolocumab and placebo groups.

Conclusions:

• PCSK9 inhibition with evolocumab effectively lowers the risk of first cardiovascular events in patients with atherosclerosis or diabetes without a history of myocardial infarction or stroke.
• Evolocumab represents a valuable therapeutic option for primary prevention of cardiovascular events in selected high-risk patients.