Efficacy and Safety of Long-Term Evolocumab Use Among Asian Subjects - A Subgroup Analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Trial

Circ J. 2021 Oct 25;85(11):2063-2070. doi: 10.1253/circj.CJ-20-1051. Epub 2021 May 15.

Abstract

Background: There are concerns that Asian patients respond differently to some medications. This study evaluated the efficacy and safety of evolocumab among Asian vs. other subjects in the FOURIER trial, which randomized stable atherosclerosis patients to receive either evolocumab or placebo.

Methods and results: Effects of adding evolocumab vs. placebo to background statin therapy on low-density lipoprotein cholesterol (LDL-C) reductions, cardiovascular outcomes, and adverse events were compared among 27,564 participants with atherosclerotic disease, according to self-reported Asian (n=2,723) vs. other (n=24,841) races followed for a median of 2.2 years in the FOURIER trial. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. At randomization, Asians had slightly lower LDL-C (median 89 [IQR 78-104] mg/dL vs. 92 [80-109] mg/dL; P<0.001) and were much less likely to be on a high-intensity statin (33.3% vs. 73.3%; P<0.001). Evolocumab lowered LDL-C more in Asians than in others (66% vs. 58%; P<0.001). The effect of evolocumab on the primary endpoint was similar in Asians (HR, 0.79; 95% CI, 0.61-1.03) and others (HR, 0.86; 95% CI, 0.79-0.93; P interaction=0.55). There was no excess of serious adverse events with evolocumab among Asians over others.

Conclusions: Use of evolocumab robustly lowers LDL-C and is equally efficacious in lowering the risk of cardiovascular events and safe in Asians as it is in others.

Trial registration: ClinicalTrials.gov NCT01764633.

Keywords: Asians; Evolocumab; LDL cholesterol; PCSK9 inhibitor.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Asian People*
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / ethnology
  • Cholesterol, LDL
  • Heart Disease Risk Factors
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • PCSK9 Inhibitors* / adverse effects
  • Proprotein Convertase 9
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PCSK9 Inhibitors
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • evolocumab

Associated data

  • ClinicalTrials.gov/NCT01764633