J Cardiovasc Pharmacol Ther. 2026 Jan-Dec;31:10742484261483397. doi: 10.1177/10742484261483397. Epub 2026 Aug 27.
ABSTRACT
BackgroundPlatelet reactivity varies after ST-segment-elevation myocardial infarction (STEMI). We evaluated serial platelet function-guided P2Y12 modulation after a 1-month ticagrelor run-in.MethodsAt month 1, 114 patients were randomized to continued ticagrelor (n=59) or an adenosine diphosphate (ADP)-guided strategy (n=55). Month-1 ADP was the preintervention baseline; months 2, 3, 6, 9, and 12 were analyzed using baseline-adjusted generalized estimating equations. Exploratory net adverse clinical events (NACE) were assessed from randomization through month 12 after STEMI.ResultsIn the guided group, month-1 ADP was 52 U (range, 4-466); 37 patients received clopidogrel 75 mg and 18 received 150 mg, with 17 dose-threshold discordances. Adjusted postrandomization ADP was higher with the guided strategy (geometric mean ratio, 1.26; 95% confidence interval [CI], 1.05-1.51). NACE occurred in 14/59 versus 4/55 patients (risk ratio [RR], 0.31; 95% CI, 0.11-0.87; absolute risk difference, -16.5 percentage points; exact P=.020). Any investigator-classified BARC bleeding occurred in 13/59 versus 3/55 (RR, 0.25; 95% CI, 0.07-0.82; exact P=.014), and the post hoc ischemic-or-BARC ≥2 composite in 9/59 versus 2/55 (RR, 0.24; 95% CI, 0.05-1.06; exact P=.055). One ischemic event occurred in each group.ConclusionsSerial ADP-guided modulation produced pharmacodynamic separation and was associated with fewer investigator-recorded, bleeding-driven events. Dose-threshold deviations, unverified extreme ADP values, incomplete BARC 2 documentation, and only 2 ischemic events restrict interpretation to hypothesis generation; efficacy and safety cannot be established.
PMID:42658178 | DOI:10.1177/10742484261483397