Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery.

Abstract

BACKGROUND:

Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death.

OBJECTIVES:

This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab).

METHODS:

Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. The primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003).

RESULTS:

In each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]).

CONCLUSIONS:

Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).

• Authors: Shaun G Goodman, Philip E Aylward, Michael Szarek, Vakhtang Chumburidze, Deepak L Bhatt, Vera A Bittner, Rafael Diaz, Jay M Edelberg, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Sasko Kedev, Alexia Letierce, Angele Moryusef, Robert Pordy, Gabriel Arturo Ramos López, Matthew T Roe, Margus Viigimaa, Harvey D White, Andreas M Zeiher, Ph Gabriel Steg, Gregory G Schwartz, ODYSSEY OUTCOMES Committees and Investigators
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 74 Issue 9 Pg. 1177-1186 (09 03 2019) ISSN: 1558-3597 [Electronic] United States
• PMID: 31466614 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• alirocumab

Topics

• Acute Coronary Syndrome (surgery)
• Aged
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Cardiovascular Diseases (prevention & control)
• Coronary Artery Bypass
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Male
• Middle Aged
• Postoperative Complications (prevention & control)