"Evolocumab in Patients with Cardiovascular Disease".The New England Journal of Medicine. 2017. 376:1713-1722.PubMed•Full text•PDF

Contents

1Clinical Question
2Bottom Line
3Major Points
4Guidelines
5Design
6Population
6.1Inclusion Criteria
6.2Exclusion Criteria
6.3Baseline Characteristics
7Interventions
8Outcomes
8.1Primary Outcome
8.2Secondary Outcomes
9Criticisms
10Funding
11Further Reading

Clinical Question

In patients with established cardiovascular disease and elevated LDL cholesterol levels despite statin therapy, does evolocumab further reduce cardiovascular events?

Bottom Line

Among patients with cardiovascular disease and elevated LDL cholesterol levels on statin therapy, the addition of evolocumab further reduced LDL cholesterol and cardiovascular events.

Major Points

While statins have significantly reduced cardiovascular events through LDL cholesterol lowering, not all patients reach target LDL cholesterol levels with statins alone. Evolocumab, a monoclonal antibody inhibiting PCSK9, has been shown to lower LDL cholesterol by approximately 60%. Its cardiovascular event reduction potential was unclear.

Guidelines

As of 2017, no guidelines reflecting the outcomes of this trial have been published.

Design

Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
N=27,564 patients with established cardiovascular disease and LDL cholesterol ≥70 mg/dL
Evolocumab at either 140 mg every 2 weeks or 420 mg monthly (n=13,784)
Placebo (n=13,780)
Median follow-up: 2.2 years
Primary efficacy outcome: Composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization

Population

Inclusion Criteria
Age 40-85 years
Clinical evidence of atherosclerotic cardiovascular disease (MI, nonhemorrhagic stroke, symptomatic peripheral artery disease)
LDL cholesterol ≥70 mg/dL or non-HDL cholesterol ≥100 mg/dL on statin therapy
Exclusion Criteria
Not specified
Baseline Characteristics
Mean age: 63 years
Female: 24.6%
History of MI: 81.1%
Previous stroke: 19.4%
Symptomatic peripheral artery disease: 13.2%
Use of high-intensity statin therapy: 69.3%
Use of ezetimibe: 5.2%

Interventions

Randomization to receive subcutaneous injections of evolocumab or matching placebo

Outcomes

Primary Outcome
Primary composite endpoint: 9.8% in evolocumab vs. 11.3% in placebo (HR 0.85; 95% CI, 0.79 to 0.92; P<0.001)
Secondary Outcomes
Key secondary composite endpoint (cardiovascular death, MI or stroke): 5.9% in evolocumab vs. 7.4% in placebo (HR 0.80; 95% CI, 0.73 to 0.88; P<0.001)
Other individual outcomes: Significant reductions for MI, stroke, and coronary revascularization
No significant effect on cardiovascular mortality, hospitalization for unstable angina, overall death, or urgent revascularization

Criticisms

Relatively short follow-up duration compared to other lipid-lowering trials
The majority but not all patients on high-intensity statin therapy; low ezetimibe use

Funding

Supported by Amgen, the manufacturer of evolocumab.

Further Reading

Additional references cited within the full text of the article and further data available in the supplementary material published alongside the article.