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Eur Heart J. 2019 Sep 1;40(33):2801-2809. doi: 10.1093/eurheartj/ehz299.

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial.

Author information

1
Green Lane Cardiovascular Services, Auckland City Hospital, 5 Park Road, Grafton, Auckland, New Zealand.
2
FACT (French Alliance for Cardiovascular Trials), an F-CRIN network, Département Hospitalo-Universitaire FIRE, AP-HP, Hôpital Bichat, Université Paris-Diderot, Sorbonne Paris-Cité, INSERM U-1148, 46 rue Henri Huchard, Paris, France.
3
National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, Sydney Street, London, UK.
4
Department of Epidemiology and Biostatistics, SUNY Downstate Medical Center School of Public Health, 450 Clarkson Avenue, Brooklyn, USA.
5
Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, 75 Francis Street, Boston, USA.
6
Division of Cardiovascular Disease, University of Alabama at Birmingham, 701 19th Street South - LHRB 310, Birmingham, USA.
7
Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Paraguay 160, Rosario, Santa Fe, Argentina.
8
Sanofi, 55 Corporate Drive, Bridgewater, USA.
9
Latvian Centre of Cardiology, Pauls Stradins Clinical University Hospital, University of Latvia, Pilsonu Street 13, Riga, Latvia.
10
Canadian VIGOUR Centre, 2-132 Li Ka Shing Centre for Health Research Innovation University of Alberta, Edmonton, Alberta, Canada.
11
St. Michael's Hospital, 30 Bond Street, University of Toronto, Toronto, ON, Canada.
12
Sanofi, 54-56 Rue la Boétie, Paris, France.
13
Stanford Center for Clinical Research, Department of Medicine, 300 Pasteur Drive, S-102, Stanford, CA, USA.
14
Department of Cardiology, Leiden University Medical Center, RC Leiden, The Netherlands.
15
Duke Clinical Research Institute, 200 Morris Street, Durham, NC, USA.
16
Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Grant S-102, Stanford, CA, USA.
17
Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, USA.
18
Department of Medicine, Faculty of Medicine, Ramathibodi Hospital/Mahidol University, Rama VI Road, Thailand.
19
CSL Behring, 1100 N Miami Blvd Ste 613, Durham, NC, USA.
20
Department of Medicine III, Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main, Germany.
21
Division of Cardiology, University of Colorado School of Medicine, 1700 N. Wheeling Street, Aurora, CO, USA.

Abstract

AIMS :

The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin-kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI.

METHODS AND RESULTS :

Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77-0.99; P = 0.032) and Type 2 (0.77, 0.61-0.97; P = 0.025), but not Type 4 MI.

CONCLUSION :

After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.

KEYWORDS:

Alirocumab; MI types; Mortality; Prevention

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