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J Am Coll Cardiol. 2020 Jan 28;75(3):289-300. doi: 10.1016/j.jacc.2019.11.035.

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

Author information

1
Thrombosis In Myocardial Infarction Study Group-Brigham and Women's Hospital, Boston, Massachusetts; Instituto do Coracao (InCor), Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
2
Instituto do Coracao (InCor), Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
3
Thrombosis In Myocardial Infarction Study Group-Brigham and Women's Hospital, Boston, Massachusetts.
4
Duke Clinical Research Institute, Durham, North Carolina.
5
Thrombosis In Myocardial Infarction Study Group-Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: rgiugliano@bwh.harvard.edu.

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).

KEYWORDS:

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

PMID:
31976867
DOI:
10.1016/j.jacc.2019.11.035

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