Polish trials influencing 2017 European Society of Cardiology guidelines on acute myocardial infarction in patients presenting with ST-segment elevation

During the latest annual European Society of Cardiology Congress in Barcelona, new guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation (STEMI) were presented [1]. It is noteworthy that, apart from international, multicenter studies involving sites from Poland, the results of three Polish trials had a significant impact on the shape of the current recommendations on the management of STEMI patients [2–4].
Alleviation of chest pain is one of the main therapeutic targets in patients presenting with STEMI, and titrated intravenous morphine is a routinely administered analgesic in this setting. However, a recent paper by Kubica et al. revealed that morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction [2]. The randomized, double-blind, placebo-controlled IMPRESSION trial, conducted in the Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University in Bydgoszcz, aimed to evaluate the influence of infused morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite in patients with acute myocardial infarction. Seventy patients were assigned in a 1 : 1 ratio to receive either morphine (5 mg) or placebo intravenously followed by a 180 mg loading dose of ticagrelor. Morphine lowered the total exposure to ticagrelor and its active metabolite by 36% (AUC(0–12): 6307 vs. 9791 ng * h/ml; p = 0.003) and 37% (AUC(0–12): 1503 vs. 2388 ng * h/ml; p = 0.008), respectively. Moreover, a delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; p = 0.004) was observed in patients receiving morphine. Multiple regression analysis showed that lower AUC(0–12) values for ticagrelor were independently associated with the administration of morphine (p = 0.004) and the presence of STEMI (p = 0.014). In pharmacodynamic assessment up to three platelet reactivity tests were used – the vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode aggregometry and VerifyNow – and all of them revealed a stronger antiplatelet effect in the placebo group and a greater prevalence of high platelet reactivity in the morphine arm. Despite the results of the IMPRESSION study clearly showing a negative impact of morphine on bioavailability and antiplatelet action of ticagrelor, due to lack of effective alternative, titrated intravenous opioids should be considered to relieve pain in STEMI patients....


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