Abstract
Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.
Highlights
Excessive platelet activation and aggregation play essential role in the pathophysiology of acute coronary syndromes (ACS), including acute myocardial infarction (AMI)[1]
According to both European and American guidelines, it is the first line of treatment in a wide spectrum of ACS patients, including patients with ST-elevation myocardial infarction (STEMI) and moderate-to-high-risk non-ST-elevation ACS (NSTE-ACS), regardless of initial treatment strategy and including those pretreated with clopidogrel[3,4,5,6]
A multiple regression analysis confirmed that both diagnosis of STEMI
Summary
Excessive platelet activation and aggregation play essential role in the pathophysiology of acute coronary syndromes (ACS), including acute myocardial infarction (AMI)[1]. Ticagrelor is a potent, reversibly binding, noncompetitive, oral P2Y12 receptor antagonist[7] It is characterized by linear pharmacokinetics, and unlike other available P2Y12 receptor inhibitors administered orally, it does not necessitate metabolic activation to exert its antiplatelet action[8]. Ticagrelor may increase bioavailability of some statins, currently there are no data indicating that any of the medications routinely used for the treatment of ACS may affect metabolism of ticagrelor[22]. This applies to morphine, the elementary analgesic used to relive chest pain in patients with ACS21. It remains obscure what causes this discrepancy in the bioavailability of AR-C124910XX between healthy subjects and patients with ACS
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