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Morphine in Non-ST-Segment Elevation ACS
Study Questions:
What is the association between morphine and ischemic events in patients treated with concomitant clopidogrel presenting with non-ST-segment elevation acute coronary syndromes (NSTEACS)?
Methods:
The investigators conducted a post hoc subanalysis from the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome) trial, which randomly assigned high-risk patients with NSTEACS to early (i.e., before coronary angiography) versus delayed, provisional (during or soon after percutaneous coronary intervention) use of the intravenous glycoprotein IIb/IIIa antagonist eptifibatide. The primary population of interest for this analysis comprised those patients who were treated with clopidogrel within 24 hours before randomization. Endpoints were the composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout at 96 hours (four-way endpoint) and the composite of death or MI at 30 days. For the landmark analysis, the authors used a multivariable Cox proportional hazards model to derive hazard ratios (HRs) and confidence intervals (CIs). Schoenfeld residuals confirmed the proportional hazards assumption.
Results:
In patients treated with clopidogrel, morphine use was associated with higher rates of the four-way endpoint at 96 hours (adjusted odds ratio [OR], 1.40; 95% CI, 1.04-1.87; p = 0.026). There was a trend for higher rates of death or MI at 30 days (adjusted OR, 1.29; 95% CI, 0.98-1.70; p = 0.072), driven by events in the first 48 hours (adjusted HR, 1.54; 95% CI, 1.07-2.23; p = 0.021). In patients not treated with clopidogrel, morphine was not associated with either the four-way endpoint at 96 hours (adjusted OR, 1.05; 95% CI, 0.74-1.49; p = 0.79; pinteraction = 0.36) or death or MI at 30 days (adjusted OR, 1.07; 95% CI, 0.77-1.48; p = 0.70; pinteraction = 0.46).
Conclusions:
The authors concluded that when used concomitantly with clopidogrel pretreatment, morphine was associated with higher rates of ischemic events in patients with NSTEACS.
Perspective:
This study reports that morphine used concomitantly with clopidogrel pretreatment was associated with higher short-term risk of acute ischemic events among patients with invasively managed NSTEACS. Based on these results, it appears that a higher risk of ischemic events with morphine restricted to patients treated with concomitant clopidogrel is most likely explained by a clinical interaction between these drugs, which is also consistent with pharmacological studies. Given the post hoc nature of this analysis, additional studies are indicated to verify these results and to further define the pharmacological interactions between analgesic and antithrombotic medications in patients with acute coronary syndromes.
Clinical Topics: Acute Coronary Syndromes, Cardiovascular Care Team, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging
Keywords: Acute Coronary Syndrome, Coronary Angiography, Fibrinolytic Agents, Morphine, Myocardial Infarction, Myocardial Ischemia, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Platelet Glycoprotein GPIIb-IIIa Complex, Primary Prevention, Thrombosis
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