Effect of morphine use on oral P2Y12 platelet inhibitors in acute myocardial infarction: Meta-analysis

Abstract

Background: Morphine is the recommended analgesic in acute myocardial infarction (AMI). This recommendation has come under scrutiny because of possible slow uptake of oral antiplatelet agents. Objective: We performed a meta-analysis of all available studies in AMI patients treated with prasugrel or ticagrelor (P2Y12 inhibitors) that reported use of morphine prior to loading the antiplatelet agents to critically assess the safety of co-administration of morphine and the newer P2Y12 inhibitors. Methods: Several sources were searched from inception to December 2017 with inclusion of eight studies, largely observational. Mean difference (MD) was calculated for continuous variables, and standardized mean difference (SMD) for platelet function was assessed by the various platelet assays, 2 h after the loading dose of oral P2Y12 inhibitors. Results: Higher platelet activity was noted among morphine group [SMD = 0.8, 95% confidence interval (CI) = 0.4–1.1, p < 0.01]. Morphine use caused higher odds of “high residual platelet reactivity” at 2 h (odds = 3.3, 95 %CI = 2.2–5.1, p < 0.01). Ticagrelor reached a lower plasma concentration in morphine group (MD = −481.8 ng/ml, 95% CI = −841.2 to −122.4 ng/ml, p < 0.01) with a higher vomiting rate (odds = 5.3, 95% CI = 2.5–11.1, p < 0.01). However, the composite of in-hospital mortality, stroke, and re-infarction was not significantly different between the groups (p = 0.83). Conclusion: Co-administration of morphine with P2Y12 inhibitors possibly decreases their efficacy in platelet inhibition. However, this did not translate into higher adverse outcomes because of low event rates, inadequate for analysis. A large randomized study is needed to evaluate the narcotic-P2Y12 interaction. Keywords: Morphine, STEMI, Myocardial infarction, Ticagrelor, Prasugrel, Platelets, Absorption, Platelet activity, Opioid, Chest pain, Death, Revascularization, Stent thrombosis