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

Circ Cardiovasc Interv. 2014 Dec 31;8(1):e001593. doi: 10.1161/CIRCINTERVENTIONS.114.001593. Print 2015 Jan.

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.

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.

Keywords: infarction; morphine; platelets; prasugrel; stent; ticagrelor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Ticagrelor

Substances

  • Analgesics, Opioid
  • Piperazines
  • Platelet Aggregation Inhibitors
  • Thiophenes
  • Morphine
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Adenosine