Comparison of platelet inhibition in patients with acute coronary syndrome treated with morphine vs. no morphine after a loading dose of swallowed vs. chewed ticagrelor

Background: Dual anti-platelet therapy represents standard care for treating patients with acute coronary syndromes (ACS). Ticagrelor is a direct-acting P2Y12 inhibitor and does not require metabolic activation. Over the past few years there has been some concern raised about the drug-drug interactions of morphine with antiplatelet agents and delayed gastric absorption causing impaired platelet inhibition as well as an association with worsened clinical outcomes.

Methods: We prospectively compared platelet inhibition in response to a ticagrelor loading dose (180mg) in 100 consecutive ACS patients [both ST-elevation (n=50) and non-ST-elevation (n=50) myocardial infarction (STEMI/NSTEMI)]. Patients were either treated by morphine (M) (n=17) or not (NM) (n=83). A ticagrelor loading dose was either swallowed (n=50) or chewed (n=50). Platelet inhibition was determined in response to ADP by VerifyNow and expressed as PRU at baseline, 1 hour, and 4 hours after loading dose.

Results: There were no differences in baseline characteristics between patients in both groups. Platelet reactivity was higher at 1 hour in the M group vs. NM groups regardless of whether ticagrelor was swallowed (233±25 vs. 140±92, p<0.01) or chewed (156±112 vs. 57±56, p<0.001). Nevertheless, at 4 hours platelet reactivity was higher in the M group if ticagrelor was swallowed (96±107 vs. 47±58, p=0.03) but not if it was chewed (59±53 vs. 37±33, p=0.06). Moreover, infarct size (as measured by lower left ventricular ejection fraction and higher peak troponin level) was larger among the M group (45%±11 vs. 51%±11, p=0.02 and 41±29 mic/l vs. 15±19 mic/l, p<0.001, respectively), as was the number of vessel disease by angiography (2.06 vs. 1.57, p=0.02).

Conclusions: Our findings suggest that beyond drug-drug interaction and delayed gastric absorption of ticagrelor, there is also association to platelet hypo-responsiveness that might be related to the extent of the myocardial infarction and thrombus burden in patients treated with morphine.