Original Investigation
Morphine and Cardiovascular Outcomes Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing Coronary Angiography

https://doi.org/10.1016/j.jacc.2019.11.035Get rights and content
Under an Elsevier user license
open archive

Abstract

Background

Mechanistic studies have shown that morphine blunts the antiplatelet effects of oral adenosine diphosphate receptor blockers. However, the clinical relevance of this interaction is controversial.

Objectives

This study sought to explore the association between morphine and ischemic events in 5,438 patients treated with concomitant clopidogrel presenting with non-ST-segment elevation acute coronary syndromes (NSTEACS) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome) trial. Patients not treated with clopidogrel (n = 3,462) were used as negative controls.

Methods

Endpoints were the composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout at 96 h (4-way endpoint) and the composite of death or MI at 30 days.

Results

In patients treated with clopidogrel, morphine use was associated with higher rates of the 4-way endpoint at 96 h (adjusted odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.04 to 1.87; p = 0.026). There was a trend for higher rates of death or MI at 30 days (adjusted OR: 1.29; 95% CI: 0.98 to 1.70; p = 0.072), driven by events in the first 48 h (adjusted hazard ratio: 1.54; 95% CI: 1.07 to 2.23; p = 0.021). In patients not treated with clopidogrel, morphine was not associated with either the 4-way endpoint at 96 h (adjusted OR: 1.05; 95% CI: 0.74 to 1.49; p = 0.79; pinteraction = 0.36 ) or death or MI at 30 days (adjusted OR: 1.07; 95% CI: 0.77 to 1.48; p = 0.70; pinteraction = 0.46).

Conclusions

When used concomitantly with clopidogrel pre-treatment, morphine was associated with higher rates of ischemic events in patients with NSTEACS. (EARLY ACS: Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome; NCT00089895)

Key Words

ADP receptor blocker
clopidogrel
drug interaction
non-ST-segment elevation ACS
opioids

Abbreviations and Acronyms

ACS
acute coronary syndromes
ADP
adenosine diphosphate
CI
confidence interval
FDA
U.S. Food and Drug Administration
IPTW
inverse probability of treatment weighting
MI
myocardial infarction
NSTEACS
non–ST-segment elevation acute coronary syndromes
OR
odds ratio
STEMI
ST-segment elevation myocardial infarction
TIMI
Thrombolysis In Myocardial Infarction

Cited by (0)

The EARLY ACS trial received grant funding from Schering-Plough. The work of Dr. Furtado was supported by the Lemann Foundation Cardiovascular Research Postdoctoral Fellowship, Harvard University/Brigham and Women’s Hospital. The current analyses received no sources of external funding. Dr. Furtado has received honoraria from AstraZeneca; and has received research grants from AstraZeneca, DalCor, Boehringer Ingelheim, Pfizer, Bayer, and Sanofi. Dr. Nicolau has received research grants from Amgen Inc., Bayer Healthcare Pharmaceuticals, Bristol-Myers Squibb Company, CLS Behring, DalCor, Janssen Pharmaceuticals Inc., Novartis, Population Research Institute, Novo Nordisk, Sanofi, and AstraZeneca; and has served as a consultant/on the advisory board for Bayer, Daiichi-Sankyo, Novartis, Servier, and Sanofi. Dr. Guo has received research grants from Merck. Dr. Im has received research grants from Merck; and is a member of the Thrombosis In Myocardial Infarction Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Aralez, AstraZeneca, Bayer HealthCare Pharmaceuticals Incl., BRAHMS, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company, and Zora Biosciences. Dr. Sabatine has received research grant support through Brigham and Women’s Hospital from Abbott Laboratories, Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, Gilead, GlaxoSmithKline, Intarcia, Janssen Research and Development, The Medicines Company, MedImmune, Merck, Novartis, Poxel, Pfizer, Quark Pharmaceuticals, Roche Diagnostics, and Takeda; is a member of the Thrombosis In Myocardial Infarction Study Group, which has also received institutional research grant support through Brigham and Women’s Hospital from Abbott, Aralez, Roche, and Zora Biosciences; and has received consulting fees from Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor, Dyrnamix, Esperion, IFM Therapeutics, Intarcia, Ionis, Janssen Research and Development, The Medicines Company, MedImmune, Merck, MyoKardia, and Novartis. Dr. Newby has received a research grant from Boehringer Ingelheim; and has served as a consultant/on the advisory board for Roche Diagnostics, Ortho-Clinical Diagnostics, Quidel, BioKier, Bristol-Myers Squibb, and CSL. Dr. Giugliano has received research grants from Amgen, Daiichi-Sankyo, and Merck; has received honoraria from Amgen, Daiichi-Sankyo, and Merck; has provided CME lectures for Amgen, Daiichi-Sankyo, Merck, and Servier; and has served as a consultant/on the advisory board for Akcea, Amarin, American College of Cardiology, Amgen, Angel Med, Beckman-Coulter, Boehringer Ingelheim, Bristol-Myers Squibb, CVS Caremark, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Lexicon, Merck, Portola, Pfizer, St. Jude, and Stealth Peptides. Ms. White has reported that she has no relationships relevant to the contents of this paper to disclose.

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