"Evolocumab in Patients with Cardiovascular Disease".The New England Journal of Medicine. 2017. 376:1713-1722.
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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
In patients with established cardiovascular disease and elevated LDL cholesterol levels despite statin therapy, does evolocumab further reduce cardiovascular events?
Among patients with cardiovascular disease and elevated LDL cholesterol levels on statin therapy, the addition of evolocumab further reduced LDL cholesterol and cardiovascular events.
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.
The FOURIER trial randomized 27,564 patients with established atherosclerotic cardiovascular disease and LDL cholesterol levels ≥70 mg/dL (1.8 mmol/L) despite statin therapy to receive either evolocumab or placebo. At 48 weeks, evolocumab reduced LDL cholesterol levels by 59% compared to placebo. After a median follow-up of 2.2 years, evolocumab reduced the risk of the primary composite endpoint (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) by 15%. The treatment effect appeared to increase over time.
As of 2017, no guidelines reflecting the outcomes of this trial have been published.
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
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%
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
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
Supported by Amgen, the manufacturer of evolocumab.
Additional references cited within the full text of the article and further data available in the supplementary material published alongside the article.