P2Y12 receptor inhibition and effect of morphine in patients undergoing primary PCI for ST-segment elevation myocardial infarction

Abstract

PRIVATE-ATLANTIC (P2Y12 Receptor Inhibition with VASP Testing using Elisa kit during the ATLANTIC study) is a pre-specified substudy of the randomised, double-blind ATLANTIC trial in patients with ST-segment elevation myocardial infarction, designed to help interpret the main trial results. The primary objective of ATLANTIC was to assess coronary reperfusion prior to percutaneous coronary intervention (PCI) with pre- vs in-hospital ticagrelor 180 mg loading dose (LD). PRIVATE-ATLANTIC assessed platelet inhibition in 37 patients by measurement of vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) and VerifyNow platelet reactivity units (PRU) before angiogram (T1), immediately after PCI (T2), 1 (T3), and 6 (T4) hours (h) after PCI, and before next study drug administration (T5). The median time difference between the two ticagrelor LD was 41 minutes. Platelet reactivity was unaffected at T1 when measured by VASP-PRI (89.8 vs 93.9 % for pre- and in-hospital ticagrelor, respectively; p = 0.18) or PRU (239 vs 241; p = 0.82). Numerical differences were apparent at T2 and maximal at T3. Morphine administration significantly delayed onset of platelet inhibition at T3 (VASP-PRI 78.2 vs 23.4 % without morphine; p = 0.0116) and T4 (33.1 vs 11.0 %; p = 0.0057). In conclusion, platelet inhibition in ATLANTIC was unaffected by pre-hospital ticagrelor administration at the time of initial angiogram due to the short transfer delay. The maximum difference in platelet inhibition was detected 1 h after PCI (T3). Morphine administration was associated with delayed onset of action of ticagrelor and appeared more important than timing of ticagrelor administration.

International Expert Consensus on Switching Platelet P2Y 12 Receptor–Inhibiting Therapies

“…Infusions up to 4 hours might be considered particularly in patients treated with opiates such as morphine (terminal half-life varies from 1.5-4.5 hours) and possibly in patients undergoing primary PCI, which are settings known to reduce the pharmacodynamic onset of oral antiplatelet agents. [88][89][90][91] These observations are likely attributed to impaired gastrointestinal motility and drug absorption, which can be accentuated in patients undergoing primary PCI. 92 In the transition from cangrelor to a thienopyridine, the thienopyridine should be administered immediately after discontinuation of cangrelor with an LD (clopidogrel 600 mg or prasugrel 60 mg) to avoid a potential DDI.…”

P2Y 12 Receptor Antagonists and Morphine

“…Delayed onset of action when ticagrelor was coadministered with morphine was also reported in another study in 37 STEMI patients, where morphine administration was associated with significantly higher platelet reactivity at 1 and 6 hours after the loading dose of ticagrelor. 13 The same, by and large, was shown for prasugrel in a small crossover study of 11 patients with a history of STEMI in the past 12 months, 14 which showed increased platelet reactivity from 30 minutes ≤2 hours after the loading dose when morphine was coadministered, both in terms of absolute platelet reaction units and percent platelet inhibition. The estimated time to achieve adequate platelet inhibition (platelet reactivity units <208) was 150 minutes with morphine versus 68 minutes without (P=0.006).…”

Cangrelor for the management and prevention of arterial thrombosis

“…Opiates also delay gastric emptying and therefore can delay the absorption and onset of action of oral P2Y 12 inhibitors, which rely on intestinal absorption [27][28][29][30]. Vomiting of stomach contents may lead to uncertainty about absorption of oral therapy and patients can also be unable to swallow e.g.…”