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Long-Term Efficacy of Evolocumab in Patients With or Without Multivessel Coronary Disease
Daniel J McClintick1, Michelle L O'Donoghue2, Gaetano M De Ferrari3
1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Background:
In FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), during a median follow-up of 2.2 years, risk reduction for major adverse cardiovascular event with evolocumab was greater in patients with multivessel disease (MVD). The FOURIER Open-Label Extension (FOURIER-OLE) provides an additional median follow-up of 5 years.
Objectives:
The purpose of this study was to assess the long-term benefit of evolocumab in patients with and without MVD.
Methods:
FOURIER randomized 27,564 patients to evolocumab vs placebo; 6,635 entered FOURIER-OLE. Patients with coronary artery disease were categorized based on the presence of MVD (≥40% stenosis in ≥2 large vessels). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization; the key secondary endpoint was cardiovascular death, myocardial infarction, or stroke.
Results:
Of 23,656 patients in FOURIER with coronary artery disease, 25.4% had MVD; 5,887 patients continued into FOURIER-OLE. The risk reduction with initial allocation to evolocumab tended to be greater in patients with MVD than in those without: 23% (HR: 0.77 [95% CI: 0.68-0.87]) vs 11% (HR: 0.89 [95% CI: 0.82-0.96]) for the primary and 31% (HR: 0.69 [95% CI: 0.59-0.81]) vs 15% (HR: 0.85 [95% CI: 0.77-0.94]) for the key secondary endpoints (Pinteraction = 0.062 and Pinteraction = 0.031, respectively). The magnitude of benefit tended to grow during the first several years, reaching 37% to 38% reductions in risk in patients with MVD and 23% to 28% reductions in risk in patients without MVD.
Conclusions:
Evolocumab reduced the rate of major adverse cardiovascular event in patients with and without MVD. The benefit tended to occur earlier and was larger in patients with MVD. However, the magnitude grew over time in both groups. These data support early initiation of intensive low-density lipoprotein cholesterol lowering both in patients with and without MVD.
Insights
Evolocumab significantly reduced major cardiovascular events in patients with multivessel disease (MVD) and without. The drug
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Clinical Trials
Background:
- The FOURIER trial demonstrated evolocumab's efficacy in reducing cardiovascular events.
- Patients with multivessel disease (MVD) showed a greater risk reduction with evolocumab.
- The FOURIER Open-Label Extension (FOURIER-OLE) extended follow-up for long-term benefit assessment.
Purpose of the Study:
- To evaluate the long-term cardiovascular benefits of evolocumab in patients with and without MVD.
- To compare the efficacy of evolocumab in patient subgroups based on the presence of MVD.
Main Methods:
- FOURIER randomized 27,564 patients; 6,635 entered the FOURIER-OLE.
- Patients were categorized by the presence of MVD (stenosis in ≥2 large vessels).
- Primary endpoint: composite of cardiovascular death, myocardial infarction, stroke, unstable angina hospitalization, or revascularization.
Main Results:
- Evolocumab demonstrated greater risk reduction in patients with MVD (23% primary, 31% key secondary) compared to those without (11% primary, 15% key secondary).
- The magnitude of benefit increased over time, with risk reductions reaching 37-38% in MVD patients and 23-28% in non-MVD patients.
- A significant interaction was observed for the key secondary endpoint (P=0.031), indicating a differential benefit based on MVD status.
Conclusions:
- Evolocumab effectively reduces major adverse cardiovascular events in both MVD and non-MVD patients.
- The cardiovascular benefit of evolocumab was more pronounced and occurred earlier in patients with MVD.
- These findings support early and intensive low-density lipoprotein cholesterol lowering with evolocumab for patients with and without MVD.
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