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

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.

• Authors: Harvey D White, Ph Gabriel Steg, Michael Szarek, Deepak L Bhatt, Vera A Bittner, Rafael Diaz, Jay M Edelberg, Andrejs Erglis, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Renato D Lopes, Kenneth W Mahaffey, Angele Moryusef, Robert Pordy, Matthew T Roe, Piyamitr Sritara, Pierluigi Tricoci, Andreas M Zeiher, Gregory G Schwartz, ODYSSEY OUTCOMES Investigators
• Journal: European heart journal (Eur Heart J) Vol. 40 Issue 33 Pg. 2801-2809 (09 01 2019) ISSN: 1522-9645 [Electronic] England
• PMID: 31121022 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Chemical References

• Antibodies, Monoclonal, Humanized
• Cholesterol, LDL
• alirocumab

Topics

• Aged
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Cholesterol, LDL (blood)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Myocardial Infarction (blood, classification, prevention & control)
• Prospective Studies