Cardiovascular outcome trial · N Engl J Med 2017
FOURIER trial
Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease.
The bottom line
Adding evolocumab to statin therapy substantially lowers LDL cholesterol and reduces cardiovascular events in patients with atherosclerotic cardiovascular disease, with injection-site reactions being the main added safety concern.
BenefitUS status: US-approved
At a glance
- Medicine
- evolocumab (either 140 mg every 2 weeks or 420 mg monthly)
- Compared with
- matching placebo
- People
- 27,564
- Who took part
- patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy
- Design
- randomized, double-blind, placebo-controlled trial
- Follow-up
- median duration of follow-up was 2.2 years
- Main question
- composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization
Main result
1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001
Effect on LDL cholesterol
least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001)
Other results
key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke): 816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001
Safety
There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%)
In the trial's own words
“Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001).”
Quoted from the abstract of N Engl J Med 2017, checked word for word against PubMed. PubMed 28304224 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Evolocumab (Repatha) and alirocumab (Praluent)
Common questions
What did the FOURIER trial find?
Adding evolocumab to statin therapy substantially lowers LDL cholesterol and reduces cardiovascular events in patients with atherosclerotic cardiovascular disease, with injection-site reactions being the main added safety concern.
Who was in FOURIER?
27,564 people. patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy.
What was FOURIER's main result?
1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001
How much did LDL cholesterol change in FOURIER?
least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001)
Related trials
- EBBINGHAUS (2017)Adding evolocumab to statin therapy did not worsen cognitive function compared with placebo over a median follow-up of 19 months.
- ORION-1 (2017)In this phase 2 trial, inclisiran produced substantial, dose-dependent, and durable reductions in LDL cholesterol and PCSK9 levels in high cardiovascular risk patients, with an acceptable safety profile, but the trial was not designed to assess cardiovascular outcomes.
- SPIRE-1/2 (2017)Bococizumab substantially lowered LDL cholesterol but showed no significant reduction in major cardiovascular events overall, with benefit seen only in the higher-risk trial, and the drug's development was discontinued due to high rates of antidrug antibodies and injection-site reactions.
- GAUSS-3 (2016)In statin-intolerant patients, evolocumab produced substantially greater LDL-C lowering than ezetimibe over 24 weeks, with fewer treatment discontinuations for muscle symptoms.
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