Abstract
BackgroundIn patients undergoing primary percutaneous coronary intervention (PPCI) ticagrelor is superior to clopidogrel in reducing cardiovascular events. This study sought to evaluate the effect of clopidogrel pretreatment on the pharmacodynamics of ticagrelor in patients undergoing PPCI.MethodsWe measured platelet reactivity using the VerifyNow P2Y12 assay at baseline, 1, 2, 4, 6, 12, 24, and 48 hours following ticagrelor bolus in patients previously loaded with clopidogrel (C+T) and in thienopyridine-naive patients (T) referred to our centre for PPCI.ResultsIn total, 52 consecutive eligible patients with ST-elevation myocardial infarction (STEMI) were enrolled (27 C+T and 25 T). Baseline characteristics and mean baseline platelet reactivity units (PRUs) were similar between the groups. The primary endpoint, the proportion of patients achieving a PRU<208 at 2 hours, was more frequently achieved in the C+T group compared to T treatment (76.0% vs 44.4%, p = 0.026). Notably, C+T therapy resulted in fewer patients with high platelet reactivity at 1 hour (56.0% vs. 14.8%), 4 hours (100.0% vs. 61.5%) and 6 hours (100.0% vs. 64%, p<0.01 for all comparisons). Furthermore, C+T therapy was associated with lower PRU values from 2 to 48 hours.ConclusionsIn patients referred for PPCI, ticagrelor bolus following clopidogrel resulted in more rapid and profound platelet inhibition, demonstrating a positive pharmacodynamic interaction. Further study is needed to determine if this pharmacodynamic effect translates into reduced clinical events.
Highlights
Patients undergoing primary percutaneous coronary intervention (PPCI) for stent thrombosis (ST)-elevation myocardial infarction (STEMI) are routinely treated with a P2Y12 inhibitor in addition to aspirin
Pharmacodynamics reported in 25 patients undergoing PPCI and treated with ticagrelor suggested that onset of antiplatelet activity may be delayed in patients with ST-elevation myocardial infarction (STEMI) [8]
Population and Baseline Characteristics From June 2012 to November 2012, 328 patients were indexed in our regional STEMI program of which 52 eligible patients were enrolled and underwent baseline and serial platelet reactivity units (PRUs) testing with the VerifyNow P2Y12 assay (Figure 1)
Summary
Patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) are routinely treated with a P2Y12 inhibitor in addition to aspirin. Pharmacodynamics reported in 25 patients undergoing PPCI and treated with ticagrelor suggested that onset of antiplatelet activity may be delayed in patients with STEMI [8]. These findings were subsequently confirmed in a second pharmacodynamic study [9]. In patients undergoing primary percutaneous coronary intervention (PPCI) ticagrelor is superior to clopidogrel in reducing cardiovascular events.
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