PCSK9i reduces CV events in patients with recent MI
Efficacy of Evolocumab on Cardiovascular Outcomes in Patients With Recent Myocardial Infarction: A Prespecified Secondary Analysis From the FOURIER Trial
Introduction and methods
The 2018 AHA/ACC multisociety guideline on the management of blood cholesterol recommends addition of a PCSK9 inhibitor to maximally tolerated statin therapy in patients with clinical atherosclerotic cardiovascular disease (ASCVD) who are at very high risk and have a LDL-c level >70 mg/dL or non-HDL-c level >100 mg/dL . Patients with recent (past 12 months) MI are considered as such very high-risk patients .
The FOURIER trial previously showed that patients with MI in the past 2 years, patients with multiple prior MIs, and patients with residual multivessel coronary disease are at greater risk of CV events and tended to have a higher risk reduction when treated with evolocumab. This prespecified secondary analysis of the FOURIER trial evaluated the risks of CV events and examined the clinical efficacy of evolocumab in patients with recent MI, compared to those with remote MI.
The FOURIER trial was a double-blind placebo-controlled randomized trial in 27564 patients with clinically evident ASCVD, LDL-c level >70 mg/dL or non-HDL-c level >100 mg/dL, and additional high-risk factors. Patients were randomized to receive either evolocumab (140 mg every 2 weeks or 420 mg every month, subcutaneous) or matching placebo [2,3]. The primary composite endpoint was CV death, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary composite endpoint was CV death, MI or stroke. For this analysis, 22320 patients (78.5% were male, mean [SD] age was 62.2 [9.0] years) were stratified as having recent MI (1-12 months prior to randomization, n=5711), or remote MI (>12 months prior to randomization, n=16609).
- In the placebo arm, the 3-year Kaplan-Meier rate for the primary endpoint was 17.2% in patients with recent MI compared with 14.4% in patients with remote MI (adjusted HR 1.45, 95%CI 1.29-1.64, P<0.001).
- The 3-year Kaplan-Meier rate for the key secondary endpoint in the placebo arm was 10.9% in the recent MI group compared with 9.5% in the remote MI group (adjusted HR 1.45, 95%CI 1.24-1.69, P<0.001).
- Evolocumab reduced the relative risk of the primary endpoint in patients with recent MI by 19% (HR 0.81, 95%CI 0.70-0.93), compared to placebo. In patients with remote MI, the relative risk reduction was 8% (HR 0.92, 95%CI 0.84-1.01, P for interaction=0.13).
- The relative risk reduction of the key secondary endpoint with evolocumab was 25% in those with recent MI (HR 0.75, 95%CI 0.62-0.91) and 15% in those with remote MI (HR 0.85, 95%CI 0.76-0.96, P for interaction=0.24).
- The ARRs over 3 years with evolocumab for the primary endpoint were 3.7% in patients with recent MI (95%CI 1.3-6.1) and 1.1% in those with remote MI (95%CI -0.6 to 2.7).The ARRs for the key secondary endpoint over 3 years were 3.2% in patients with recent MI (95%CI 1.2-5.2) and 1.3% in those with remote MI (95%CI -0.1 to 2.7).
- The NNT over 3 years to prevent 1 primary endpoint event was 27 in those with recent MI and 91 in those with remote MI.
This prespecified secondary analysis of the FOURIER trial showed that patients with a recent MI were at higher risk of CV events compared to patients with a remote MI. Those with recent MI tended to experience greater ARRs with evolocumab compared to those with remote MI.