Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk - FOURIER
Contribution To Literature:
The FOURIER trial showed that evolocumab was superior to placebo at reducing adverse cardiovascular events.
The goal of the trial was to evaluate the efficacy and safety of evolocumab, a PCSK9 inhibitor, among subjects with elevated cardiovascular risk on statin therapy.
Patients with established cardiovascular disease on statin therapy were randomized to evolocumab 140 mg subcutaneous every 2 weeks or 420 mg monthly (n = 13,784) versus placebo every 2 weeks (n = 13,780).
- Patients with established cardiovascular disease defined as prior myocardial infarction (MI), prior stroke, or symptomatic peripheral arterial disease
- On statin therapy with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl
- Total number of enrollees: 27,564 patients
- Duration of follow-up: median 26 months
- Mean patient age: 63 years
- Percentage female: 25%
- Percentage with diabetes: 37%
- Myocardial infarction or stroke within 4 weeks
- New York Heart Association class III or IV heart failure symptoms or left ventricular ejection fraction <30%
- Hemorrhagic stroke
- Uncontrolled ventricular tachycardia
- Planned revascularization within the next 3 months
- Uncontrolled hypertension
- Chronic kidney disease
- Organ transplant
- Major active infection
Other salient features/characteristics:
- 69% were on a high-intensity statin, while 30% were on a moderate-intensity statin
- Median LDL-C = 92 mg/dl
The primary outcome, incidence of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization, occurred in 12.6% of the evolocumab group versus 14.6% of the placebo group (p < 0.0001). This finding was consistent among all tested subgroups.
- Absolute reduction in LDL-C was 56 mg/dl with evolocumab versus placebo (median LDL-C = 30 mg/dl)
- Any serious adverse event: 24.8% with evolocumab versus 24.7% with placebo
A proportion of patients underwent cognitive testing (n = 1,204). Among this cohort, there was no difference between evolocumab versus placebo for a battery of cognitive tests, patient-reported everyday cognition, and physician-reported adverse cognitive events.
Among patients with elevated cardiovascular risk on statin therapy, evolocumab versus placebo was effective at reducing adverse cardiovascular events. Evolocumab was associated with marked reductions in LDL-C levels. Serious adverse events were similar between treatment groups. PCSK9 inhibition represents a novel approach to lower LDL-C levels and improves cardiovascular outcomes. However, for the duration of follow-up, there was no benefit on cardiovascular or all-cause mortality, and cost remains an issue.
Detailed testing did not reveal any adverse cognitive deficits among the evolocumab group.
Sabatine MS, Giugliano RP, Keech AC, et al., on behalf of the FOURIER Sttering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017;Mar 17:[Epub ahead of print].
Editorial: Dullaart RP. PCSK9 Inhibition to Reduce Cardiovascular Events. N Engl J Med 2017;Mar 17:[Epub ahead of print].
Presented by Dr. Marc S. Sabatine at the American College of Cardiology Annual Scientific Session (ACC 2017), Washington, DC, March 17, 2017.
EBBINGHAUS: Presented by Dr. Robert P. Giugliano at the American College of Cardiology Annual Scientific Session (ACC 2017), Washington, DC, March 18, 2017.
Keywords: ACC17, ACC Annual Scientific Session, Angina, Unstable, Antibodies, Monoclonal, Cholesterol, Cholesterol, LDL, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipoproteins, Metabolic Syndrome X, Myocardial Infarction, Peripheral Arterial Disease, Primary Prevention, Proprotein Convertases, Stroke, Subtilisins, Cognition
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