title: Morphine is associated with a delayed activity of oral antiplatelet agents in patients with ST-elevation acute myocardial infarction undergoing primary percutaneous coronary intervention.
abstract: 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.
  
  
  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.
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.). parodiguido@gmail.com.
authors.forename: Guido
authors.initials: G
authors.lastname: Parodi
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.).
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bellandi
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.).
authors.forename: Ioanna
authors.initials: I
authors.lastname: Xanthopoulou
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.).
authors.forename: Piera
authors.initials: P
authors.lastname: Capranzano
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.).
authors.forename: Davide
authors.initials: D
authors.lastname: Capodanno
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.).
authors.forename: Renato
authors.initials: R
authors.lastname: Valenti
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.).
authors.forename: Katerina
authors.initials: K
authors.lastname: Stavrou
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.).
authors.forename: Angela
authors.initials: A
authors.lastname: Migliorini
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.).
authors.forename: David
authors.initials: D
authors.lastname: Antoniucci
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.).
authors.forename: Corrado
authors.initials: C
authors.lastname: Tamburino
authors.affiliation: From the Department of Heart and Vessels, Careggi University Hospital, Florence, Italy (G.P., B.B., R.V., A.M., D. Antoniucci); Post-graduate School in Cardiology, University of Florence, Italy (G.P.); Department of Cardiology, Patras University Hospital, Patras, Greece (I.X., K.S., D. Alexopoulos); and Cardiology Department, Ferrarotto Hospital, University of Catania, Catania, Italy (P.C., D.C., C.T.).
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Alexopoulos
mesh_terms: D000208:Acute Disease; D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000367:Age Factors; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D004347:Drug Interactions; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000188:drug therapy; D062645:Percutaneous Coronary Intervention; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects; D000077486:Ticagrelor
chemical_list: D000701:Analgesics, Opioid; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D009020:Morphine; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine
keywords: infarction; morphine; platelets; prasugrel; stent; ticagrelor