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Morphine confers elevated CV event rate when used with clopidogrel in NSTEACS
Among patients with non-ST-segment elevation ACS undergoing coronary angiography who were pretreated with clopidogrel, those using morphine had higher ischemic event rates compared with nonusers, according to new data from the EARLY ACS trial.
Because mechanistic studies have shown morphine blocks antiplatelet effects of oral adenosine diphosphate receptor blockers, researchers investigated whether morphine administration affected ischemic events on patients with non-ST-segment elevation ACS (NSTEACS) who had coronary angiography. They analyzed 5,438 patients from EARLY ACS treated with clopidogrel and used 3,462 patients not treated with clopidogrel as negative controls.
Among those treated with clopidogrel, the primary outcome of death, MI, recurrent ischemia or thrombotic bailout at 96 hours occurred more often in patients using morphine than in nonusers (adjusted OR = 1.4; 95% CI, 1.04-1.87), Remo H.M. Furtado, MD, PhD, from the TIMI Study Group at Brigham and Women’s Hospital and Instituto do Coracao (InCor), Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, Brazil, and colleagues wrote.
There was a trend toward elevated risk for death or MI at 30 days in those taking morphine (adjusted OR = 1.29; 95% CI, 0.98-1.7), driven by the first 48 hours (aHR = 1.54; 95% CI, 1.07-2.23), according to the researchers.
Among patients not treated with clopidogrel, morphine use had no effect on the primary outcome (aOR = 1.05; 95% CI, 0.74-1.49; P for interaction = .36) or death/MI at 30 days (aOR = 1.07; 95% CI, 0.77-1.48; P for interaction = .46), the researchers wrote.
See the Pharmacology Consult column in the January issue of Cardiology Today for more on the interaction between opioids and oral P2Y12 inhibitors.
In a related editorial, Robert F. Storey, MD, DM, and William A.E. Parker, MD, both from the department of infection, immunity and cardiovascular disease, University of Sheffield, and the South Yorkshire Cardiothoracic Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, U.K., wrote, “Clinicians should take note of these findings when using clopidogrel in the management of ACS as part of a dual oral antiplatelet strategy.”
They advised that “when clopidogrel is used concurrently with morphine or another opiate, the results of the present analysis and prior pharmacodynamic studies suggest that a further loading dose of clopidogrel should be considered at 6 to 8 hours after the last dose of opiate to optimize the chances of achieving therapeutic levels of platelet P2Y12 inhibition.” – by Erik Swain
Disclosures: Furtado reports he received honoraria from AstraZeneca and research grants from AstraZeneca, Bayer, Boehringer Ingelheim, DalCor, Pfizer and Sanofi. Please see the study for the other authors’ relevant financial disclosures. Storey reports he has received institutional research grants/support from AstraZeneca and GlyCardial Diagnostics; has received consultant fees from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, GlyCardial Diagnostics, Haemonetics, Actelion/Idorsia, Novartis, Portola and Thromboserin; and has received honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer and Medscape. Parker reports no relevant financial disclosures.