Morphine Is Associated With a Delayed Activity of Oral Antiplatelet Agents in Patients With ST-Elevation Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

• Published in: Circulation. Cardiovascular interventions Vol. 8; no. 1
• Main Authors: Parodi, Guido, Bellandi, Benedetta, Xanthopoulou, Ioanna, Capranzano, Piera, Capodanno, Davide, Valenti, Renato, Stavrou, Katerina, Migliorini, Angela, Antoniucci, David, Tamburino, Corrado, Alexopoulos, Dimitrios
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.01.2015
• Subjects: Acute Disease; Adenosine - administration & dosage; Adenosine - adverse effects; Adenosine - analogs & derivatives; Age Factors; Aged; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Drug Interactions; Electrocardiography; Female; Humans; Male; Middle Aged; Morphine - administration & dosage; Morphine - adverse effects; Myocardial Infarction - diagnosis; Myocardial Infarction - drug therapy; Percutaneous Coronary Intervention; Piperazines - administration & dosage; Piperazines - adverse effects; Platelet Activation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Platelet Function Tests; Prasugrel Hydrochloride; Thiophenes - administration & dosage; Thiophenes - adverse effects; stent; infarction; prasugrel; ticagrelor; platelets; morphine
• ISSN: 1941-7640; 1941-7632
• DOI: 10.1161/CIRCINTERVENTIONS.114.001593

BACKGROUND—Morphine is recommended in patients with ST-segment–elevation myocardial infarction, including those undergoing primary percutaneous coronary intervention. Suboptimal antiplatelet effect during and after primary percutaneous coronary intervention is associated with increased thrombotic complications. It was hypothesized a potential drug–drug interaction between morphine and antiplatelet agents. We sought to assess platelet inhibition after a loading dose of the currently recommended antiplatelet agents in ST-segment–elevation myocardial infarction patients according to morphine use. METHODS AND RESULTS—Three hundred patients undergoing primary percutaneous coronary intervention receiving either prasugrel (n=95) or ticagrelor (n=205) loading dose had platelet reactivity assessed by VerifyNow 1, 2, and 4 hours after loading dose. Patients treated with morphine (n=95; 32%) had a higher incidence of vomit (15% versus 2%; P=0.001). P2Y12 reactivity units 2 hours after the loading dose was 187 (153–221) and 133 (102–165) in patient with and without morphine (P<0.001); the difference persisted after excluding patients with vomit (P<0.0001). High residual platelet reactivity (P2Y12 reactivity units ≥208) at 2 hours was found in 53% and 29% patients with and without morphine (P<0.001) and without difference between prasugrel and ticagrelor patients. The independent predictors of high residual platelet reactivity at 2 hours were morphine use (odds ratio, 2.91 [1.71–4.97]; P<0.0001) and age (odds ratio, 1.03 [1.01–1.05]; P=0.010). Morphine remained associated with high residual platelet reactivity after propensity score adjustment (c-statistic, 0.68; 95% confidence interval, 0.66–0.70; P=0.879 for Hosmer–Lemeshow test). CONCLUSIONS—In patients with ST-segment–elevation myocardial infarction, morphine use is associated with a delayed onset of action of the oral antiplatelet agents. This association persisted after adjusting for the propensity to receive morphine and after excluding patients with vomit.