Morphine is associated with a delayed activity of oral antiplatelet agents in patients with ST-elevation acute myocardial infarction undergoing primary PCI

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