Long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in fibrinolytic-treated STEMI patients undergoing early PCI.

Abstract

The long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in patients undergoing early percutaneous coronary intervention (PCI) after fibrinolytic therapy is unknown. From May 2014 to August 2016, 212 patients undergoing PCI within 24h of Tenecteplase (TNK), Aspirin, and Clopidogrel for ST-elevated myocardial infarction (STEMI) were randomized at four Canadian sites to receive additional Clopidogrel or Ticagrelor initiated prior to PCI. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline), at 4 and 24h post PCI, and follow-up appointment. A mixed-model analysis with time as the repeated measure and drug as the between-subjects factor was calculated using 2 separate 1 × 4 ANOVAs, with students t-tests used to compare drugs within each time point. Complete clinical follow-up data (median 115.0 days; IQR 80.3-168.8) was available in 50 patients (23.6%) randomized to either Clopidogrel (n = 23) or Ticagrelor (n = 27). Analyses revealed significant decreases in PRU from baseline to 4h (261.4 vs. 71.7; Mdiff = - 189.7; p < 0.001) to 24h (71.7 vs. 27.7; Mdiff = - 44.0; p < 0.001) to end of follow-up (27.7 vs.17.9; Mdiff = - 9.9. p = 0.016) for those randomized to Ticagrelor and significant decreases in PRU only from baseline to 4h (271.3 vs. 200.8; Mdiff = - 70.5, p = < 0.001) in patients receiving Clopidogrel, and a significantly greater proportion of patients with adequate platelet inhibition (PRU < 208) on long-term follow-up (Clopidogrel, 82.6% vs. Ticagrelor, 100.0%; p = 0.038). Our results demonstrate that in patients undergoing PCI within 24h of fibrinolysis for STEMI, Ticagrelor provides prolonged platelet inhibition compared with Clopidogrel.