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Evevident
Original paper
2017NEJMCardiology

FOURIER

Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

RCTPCSK9 inhibition / secondary prevention

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Overview

In established ASCVD on statins, evolocumab lowered LDL to very low levels and reduced cardiovascular events.

Clinical takeaway

FOURIER established evolocumab as an outcomes-positive add-on therapy for patients with established ASCVD and residual LDL risk on statins. The event reductions were mainly MI, stroke, and revascularization over relatively short follow-up.

Key result

Primary endpoint: 9.8% with evolocumab vs 11.3% with placebo; HR 0.85.

Practice impact

Use PCSK9 inhibitors for very-high-risk ASCVD patients whose LDL remains above goal despite maximally tolerated statin and usually ezetimibe.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

27,564

Follow-up

Median 2.2 years.

Geography

Multinational

Clinical question

Does adding evolocumab to statin therapy reduce cardiovascular events in patients with established ASCVD?

Population

  • Patients with clinically evident atherosclerotic cardiovascular disease and LDL cholesterol >=70 mg/dL or non-HDL cholesterol >=100 mg/dL while receiving statin therapy.

Intervention

Evolocumab added to background statin therapy.

Comparator

Placebo added to background statin therapy.

Primary outcome

Composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization.

Evolocumab reduced the primary composite cardiovascular endpoint compared with placebo.

Hazard ratio / 0.85 / CI 95% CI 0.79-0.92 / p=<0.001

Key results

  • Primary endpoint: 9.8% with evolocumab vs 11.3% with placebo; HR 0.85; 95% CI 0.79-0.92; p<0.001.
  • Key secondary endpoint: 5.9% vs 7.4%; HR 0.80; 95% CI 0.73-0.88; p<0.001.
  • LDL cholesterol fell by 59% at 48 weeks to a median of 30 mg/dL.
  • Injection-site reactions were more common with evolocumab.

Harms

  • Injection-site reactions were more common with evolocumab.

Clinical Use

When to cite

  • When justifying PCSK9 inhibitor therapy for residual LDL risk in ASCVD.

Practice impact

  • Supports PCSK9 inhibitor use in very-high-risk secondary prevention when LDL remains above goal despite other therapy.

Applicability

  • Most applicable to established ASCVD patients already on statins with residual LDL risk.

Limitations

  • Median follow-up was relatively short for mortality assessment.
  • Cost and access affect real-world implementation.
  • Trial selected patients with residual LDL risk despite statins.

Common misinterpretations

  • Do not describe FOURIER as primarily a mortality-reduction trial.

Related evidence

IMPROVE-IT - Earlier TrialODYSSEY OUTCOMES - Same Drug Class4S - Context

Citation

Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376(18):1713-1722. doi:10.1056/NEJMoa1615664

Inhibition of PCSK9 with evolocumab lowered LDL cholesterol levels and reduced cardiovascular events.