Metabolism of ticagrelor in patients with acute coronary syndromes.

© The Author(s) 2018Ticagrelor 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.Peer reviewedFinal Published versio

Beta-Blocker Therapy Early After Myocardial Infarction: A Comparison Between Medication at Hospital Discharge and Subsequent Pharmacy-Dispensed Medication

BACKGROUND: Beta-blocker (BB) therapy after myocardial infarction (MI) reduces all-cause mortality. OBJECTIVE: The aim of this study was to investigate BB dosing patterns and compliance following MI. METHODS: Using medical patient files and nationwide databases, we identified 100 patients who were discharged following MI in 2012 from Aarhus University Hospital, Denmark, and subsequently redeemed one or more BB prescriptions within 6 months. We obtained information about all BB medication prescribed at discharge and all BB prescriptions redeemed until 31 December 2013. Daily BB doses were computed as percentages of the target doses used in clinical trials documenting the efficacy of BBs after MI. Four dose groups were defined: ≤12.5, >12.5–25, >25–50, and >50 % of target dose. The proportion of patients in each dose group was ascertained at and following discharge, as was the proportion that changed dose group following discharge. RESULTS: The median study period was 400 days (interquartile range [IQR] 318–486 days). At discharge, 8 % of daily doses were >50 % of target dose while 80 % were ≤25 % of target dose. At first prescription redemption, 71.7 % of patients moved to a higher dose group (median dose change = 33.4 % [IQR 2.0–115.1]). Still, comparing final daily doses to discharge doses, 40.2 % did not change dose group (median dose change −5.7 % [IQR −18.0 to 4.2]). Only 31.5 % reached a final daily dose >50 % of target dose. CONCLUSIONS: Target dose BB treatment was infrequently achieved at discharge following MI. Despite dose up-titration early after discharge, most patients did not receive target dose BB treatment approximately 1 year following MI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40801-016-0079-0) contains supplementary material, which is available to authorized users