Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease: An Analysis from FOURIER.

Background -The FOURIER trial recently showed that the PCSK9 inhibitor evolocumab significantly reduced major vascular events in patients with stable atherosclerotic cardiovascular disease, including patients with prior MI. Within the broad group of patients with prior MI, we hypothesized that readily ascertainable features would identify subsets that derive greater clinical risk reduction with evolocumab. Methods -The 22,351 patients with a prior MI were characterized based on time from most recent MI, number of prior MIs, and presence of residual multivessel coronary artery disease (≥40% stenosis in ≥2 large vessels). The relative and absolute risk reductions in major vascular events including the primary endpoint (CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) and the key secondary endpoint (CV death, MI or stroke) with evolocumab in these subgroups were compared. Results -A total of 8402 patients (38%) were within 2 years of their most recent MI, 5285 patients (24%) had ≥2 prior MIs, and 5618 patients (25%) had residual multivessel CAD. In a multivariable adjusted model that simultaneously included all three high-risk features as well as other baseline covariates, more recent MI, multiple prior MIs, and residual multivessel coronary disease remained independent predictors of cardiovascular outcomes, with adjusted HRs for the primary endpoint of 1.37 (1.22-1.53), 1.78 (1.59-1.99) and 1.39 (1.24-1.56), all P<0.001. The relative risk reductions with evolocumab for the primary endpoint tended to be greater in the high-risk subgroups and were 20% (HR 0.80, 0.71-0.91), 18% (HR 0.82, 0.72-0.93), and 21% (HR 0.79, 0.69-0.91) for those with more recent MI, multiple prior MIs, and residual multivessel CAD, whereas they were 5% (HR 0.95, 0.85-1.05), 8% (HR 0.92, 0.84-1.02), and 7% (HR 0.93, 0.85-1.02) in those without, respectively. Given the higher baseline risk, the respective absolute risk reductions at 3 years exceeded 3% in the high-risk groups (3.4%, 3.7%, and 3.6%) vs. approximately 1% in the low-risk groups (0.8%, 1.3%, and 1.2%). Conclusions -Patients closer to their most recent MI, with multiple prior MIs or with residual multivessel CAD are at high risk for major vascular events and experience substantial risk reductions with LDL-C lowering with evolocumab.