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Brief Report
May 20, 2020

Efficacy of Evolocumab on Cardiovascular Outcomes in Patients With Recent Myocardial Infarction: A Prespecified Secondary Analysis From the FOURIER Trial

Author Affiliations
  • 1TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Cardiology Division, Geneva University Hospitals, Geneva, Switzerland
  • 3Division of Cardiology Città della Salute e della Scienza, Department of Medical Sciences, University of Torino, Turin, Italy
  • 4Department of Medicine, Cardiology and Intensive Care Medicine and Sigmund Freud University, Medical School, Vienna, Austria
  • 5Lady Davis Carmel Medical Center, Haifa, Israel
  • 6Hospital de Santa Cruz, Lisbon, Portugal
  • 7Amgen, Thousand Oaks, California
  • 8Sydney Medical School, National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia
  • 9National Heart and Lung Institute, Imperial College London, London, United Kingdom
  • 10Oslo University Hospital, Ulleval and Medical Faculty, University of Oslo, Oslo, Norway
  • 11Deputy Editor, JAMA Cardiology
JAMA Cardiol. Published online May 20, 2020. doi:10.1001/jamacardio.2020.0882
Key Points

Question  What is the efficacy of evolocumab in patients with a low-density lipoprotein cholesterol level of 70 mg/dL or greater (or non–high-density lipoprotein cholesterol level of 100 mg/dL or greater) and recent (past 12 months) myocardial infarction (MI) treated with maximally tolerated high-intensity statin?

Findings  In a prespecified secondary analysis from the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial in the subgroup of 5711 patients with a recent MI, evolocumab significantly reduced the risk of the composite outcome of cardiovascular death, MI, stroke, unstable angina, or coronary revascularization by 19%, with a number needed to treat over 3 years of 27.

Meaning  Our findings support the 2018 American Heart Association/American College of Cardiology Multisociety Guideline on the Management of Blood Cholesterol recommendations to intensify lipid-lowering treatment in patients with a recent MI.

Abstract

Importance  The 2018 American Heart Association/American College of Cardiology Multisociety Guideline on the Management of Blood Cholesterol identified patients with recent (past 12 months) myocardial infarction (MI) as very high risk, in whom a PCSK9 inhibitor is reasonable to add to maximally tolerated statin combined with ezetimibe if their low-density lipoprotein cholesterol level is 70 mg/dL or greater or non–high-density lipoprotein cholesterol level is 100 mg/dL or greater.

Objective  To examine the clinical efficacy of evolocumab in patients with recent MI.

Design, Setting, and Participants  This was a prespecified secondary analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, in which 27 564 patients with atherosclerotic cardiovascular disease treated with a statin were randomized to evolocumab vs placebo. Patients with prior MI with a known date (n = 22 320) were stratified as having a recent MI (within 12 months of randomization) or a remote MI (more than 12 months prior to randomization). Per protocol, patients with MI within 4 weeks prior to randomization were excluded from the FOURIER trial. Data were collected from February 2013 to November 2016, and data were analyzed from May 2019 to February 2020.

Main Outcomes and Measures  The primary composite end point was cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary composite end point was cardiovascular death, MI, or stroke.

Results  Of 22 320 included patients, 17 516 (78.5%) were male, and the mean (SD) age was 62.2 (9.0) years. Compared with 16 609 patients with a remote MI, 5711 patients with a recent MI were younger and more likely to be treated with high-intensity statin (77.3% [4415] vs 69.3% [11 506]). In the placebo arm, the 3-year Kaplan-Meier rate for the primary end point was 17.2% in patients with recent MI compared with 14.4% in those with remote MI (adjusted HR, 1.45; 95% CI, 1.29-1.64; P < .001). Similarly, the 3-year Kaplan-Meier rates for the key secondary end point was also higher in those with recent MI (10.9% vs 9.5%; adjusted HR, 1.45; 95% CI, 1.24-1.69; P < .001). In patients with a recent MI, evolocumab reduced the risk of the primary and key secondary end points by 19% (hazard ratio [HR], 0.81; 95% CI, 0.70-0.93) and 25% (HR, 0.75; 95% CI, 0.62-0.91), respectively. In patients with a remote MI, evolocumab reduced the risk of the primary and key secondary end points by 8% (HR, 0.92; 95% CI, 0.84-1.01; P for interaction = .13) and 15% (HR, 0.85; 95% CI, 0.76-0.96; P for interaction = .24), respectively. Given the higher event rates in patients with a recent MI, the absolute risk reductions over 3 years with evolocumab were 3.7% in those with recent MI vs 1.1% in those with remote MI for the primary end point and 3.2% vs 1.3%, respectively, for the key secondary end point.

Conclusions and Relevance  Patients with a recent MI were at higher risk of cardiovascular events and tended to experience greater absolute risk reductions with evolocumab than those with remote MIs. These findings support the concept in US and European guidelines to aggressively lower low-density lipoprotein cholesterol levels in very high-risk patients, such as those with a recent MI.

Trial Registration  ClinicalTrials.gov Identifier: NCT01764633

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