Impact of morphine dose on ticagrelor uptake and platelet inhibition in patients with ST-segment elevation myocardial infarction – A substudy from the prospective randomized MOVEMENT trial

Morphine delays ticagrelor effect in ST-segment elevation myocardial infarction (STEMI) patients, likely due to impaired gastrointestinal motility. The aim was to evaluate if the morphine dose impacts ticagrelor effect in STEMI patients presenting for percutaneous coronary intervention. The patient cohort was divided into quartiles based on morphine dose (mg/kg). Platelet inhibition was measured with vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) and high on-treatment platelet reactivity (HPR) was defined as ≥50% PRI. Blood samples for analyses of VASP PRI and plasma concentrations of morphine, ticagrelor, and AR-C124910XX were taken at baseline (arrival in the catherization lab) and one and 2 h later. The primary endpoint was PRI difference between the highest morphine dose quartile compared with the lowest morphine dose quartile 2 h after study inclusion. A total of 80 STEMI patients treated with morphine and ticagrelor were included in the study. The time from ticagrelor administration to randomization did not differ significantly between the different morphine dose quartiles, with an overall median of 44 min (interquartile range, IQR: 35–57 min). The primary outcome variable PRI at 2 h after study inclusion was significantly higher in patients in quartile 4 compared with quartile 1 (61.7% [42.4–91.2] vs. 26.6% [9.17–73.6], p = 0.024). Ticagrelor concentrations were significantly lower in both quartile 3 and 4 compared with quartile 1 at all the three timepoints. STEMI patients with higher weight-based morphine doses had significantly lower uptake and antiplatelet effect after a 180 mg loading dose ticagrelor.