Original Investigation
Nonculprit Lesion Myocardial Infarction Following Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome

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Abstract

Background

Recent emphasis on reduced duration and/or intensity of antiplatelet therapy following percutaneous coronary intervention (PCI) irrespective of indication for PCI may fail to account for the substantial risk of subsequent nontarget lesion events in acute coronary syndrome (ACS) patients.

Objectives

The authors sought to examine the effect of more potent antiplatelet therapy on the basis of the timing and etiology of recurrent myocardial infarction (MI) or cardiovascular death following PCI for ACS.

Methods

In the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38), which randomized patients to prasugrel or clopidogrel, 12,844 patients with ACS received at least 1 stent. MI and cardiovascular death were categorized as: 1) procedural (related to revascularization); 2) definite or probable stent thrombosis (ST); or 3) spontaneous (non-ST or non–procedure-related). Median follow-up was 14.5 months.

Results

Among the first events occurring within 30 days, 584 (69.0%) were procedural, 126 (14.9%) ST-related, and 136 (16.1%) spontaneous. After 30 days, 22 (4.7%) were procedural, 63 (13.5%) were ST-related, and 383 (81.8%) spontaneous. Prasugrel significantly reduced the incidence of MI or cardiovascular death for ST-related (1.0% vs. 2.1%; p < 0.001) and spontaneous events (3.9% vs. 4.8%; p = 0.012), with a directionally consistent numerical reduction for procedural events (4.4% vs. 5.1%; p = 0.078). Prasugrel increased spontaneous, but not procedural, major bleeding.

Conclusions

Long-term potent antithrombotic therapy reduces de novo (spontaneous) atherothrombotic events in addition to preventing complications associated with stenting of the culprit lesion following ACS. In patients undergoing PCI for ACS, spontaneous events predominate after 30 days, with the later-phase cardiovascular benefit of potent dual antiplatelet therapy driven largely by reducing de novo atherothrombotic ischemic events. (Comparison of Prasugrel [CS-747] and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591)

Key Words

acute coronary syndrome
clopidogrel
dual antiplatelet therapy
P2Y12
percutaneous coronary intervention
prasugrel

Abbreviations and Acronyms

ACS
acute coronary syndrome
CABG
coronary artery bypass graft
CI
confidence interval
CV
cardiovascular
DAPT
dual antiplatelet therapy
DES
drug-eluting stents
MI
myocardial infarction
NSTEMI
non–ST-segment elevation myocardial infarction
PCI
percutaneous coronary intervention
ST
stent thrombosis
STEMI
ST-segment elevation myocardial infarction
TIMI
Thrombolysis In Myocardial Infarction

Cited by (0)

The TRITON-TIMI 38 trial was sponsored by Daiichi-Sankyo and Eli Lilly. All authors are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women's Hospital from Abbott, Amgen, Aralez, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., BRAHMS, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company, and Zora Biosciences. Dr. Scirica has received consultant fees/honoraria from AbbVie, Allergan, Covance, Eisai, Elsevier Practice Update Cardiology, Esperion, Lexicon, Medtronic, NovoNordisk, Sanofi, AstraZeneca Pharmaceuticals, Biogen Idec, Boehringer Ingelheim Pharmaceuticals, Inc., Dr. Reddy's Laboratories Inc., Forest Laboratories, GE Healthcare, GlaxoSmithKline, Health@Scale, Lexicon, Merck & Co., Inc., and St. Jude Medical; has received institutional research grants from AstraZeneca, Daiichi-Sankyo, Eisai, Merck, Pfizer, and Poxel; and holds equity in Health@Scale. Dr. Bergmark has received grant support from MedImmune and Abbott Vascular; and has received consulting fees from Quark Pharmaceuticals, Abbott Vascular, Daiichi-Sankyo, Philips, and Janssen Pharmaceuticals. Dr. Morrow has received institutional grants from Novartis, Abbott Laboratories, AstraZeneca, Amgen, BRAHMS, Daiichi-Sankyo, Eisai, GlaxoSmithKline, The Medicines Company, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Roche Diagnostics, Takeda, and Zora Biosciences; and has received personal fees from Abbott Laboratories, AstraZeneca, GlaxoSmithKline, Merck, Roche Diagnostics, Peloton, Verseon, Bayer Pharma, InCarda Therapeutics, and Aralez. Dr. Antman has received institutional grant support from Daiichi-Sankyo. Dr. Bonaca has received institutional grants from AstraZeneca, Amgen, Bayer, Elly Lilly, Pfizer, and Merck; and has been a consultant/Advisory Board member for AstraZeneca, Merck, Aralez, and Bayer. Dr. Sabatine has received research grants from Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, Intarcia, Janssen Research and Development, The Medicines Company, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, and Takeda; and has served as a consultant/Advisory Board member for Amgen, Anthos Therapeutics, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor, Dr. Reddy’s Laboratories, Dyrnamix, Esperion, IFM Therapeutics, Intarcia, Janssen Research and Development, The Medicines Company, MedImmune, Merck, and Novartis. Dr. Braunwald has received institutional research grants from Daiichi-Sankyo and Eli Lilly; has received institutional research grants outside the submitted work from AstraZeneca, Merck, and Novartis; has been an uncompensated consultant and lecturer for Merck and Novartis; has been a consultant with Amgen, Novo Nordisk, and The Medicines Company; and has received lecture fees from Medscape. Dr. Wiviott has received grants from Amgen, Arena, AstraZeneca, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Merck, and Sanofi; has received consulting fees from ARENA, AstraZeneca, Aegerion, Allergan, Angelmed, Boehringer Ingelheim, Boston Clinical Research Institute, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, Eli Lilly, Icon Clinical, Janssen, Lexicon, Merck, Servier, St. Jude Medical, and Xoma; and his spouse is an employee of Merck.

Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.

∗

Dr. Scirica and Dr. Bergmark contributed equally to this work.

© 2020 by the American College of Cardiology Foundation. Published by Elsevier.