FOURIER tested evolocumab added to high-intensity statin therapy in patients with atherosclerotic cardiovascular disease. Which combination accurately states the outcome pattern?
- A LDL cholesterol fell substantially and the composite cardiovascular endpoint fell, but all-cause mortality was not significantly reduced ✓
- B LDL cholesterol rose modestly while cardiovascular events fell sharply
- C All-cause mortality fell significantly, establishing PCSK9 inhibition as first-line therapy
- D Neurocognitive adverse events led to premature termination of the trial
Correct answer: A. LDL cholesterol fell substantially and the composite cardiovascular endpoint fell, but all-cause mortality was not significantly reduced
Explanation
In FOURIER, evolocumab lowered LDL cholesterol by roughly 59% from a baseline already around 90 mg/dL on statin, and reduced the composite endpoint of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or coronary revascularization by about 15%. However, all-cause mortality was not significantly reduced, which remains the key limitation cited against universal PCSK9 inhibitor use. Neurocognitive concerns were formally examined and not confirmed.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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