ABSTRACT
BACKGROUND: Thrombin generation (TG), platelet function and circulating endothelial progenitor cells (EPCs) have an important role in the pathophysiology of coronary artery disease (CAD). To date, the effect of novel P2Y12 inhibitors on these aspects has mostly been studied in the sub-acute phase following myocardial infarction. OBJECTIVES: Comparing the effects of prasugrel and ticagrelor on TG and EPCs in the acute phase of ST-segment elevation myocardial infarction (STEMI). METHODS: STEMI patients were randomized to either ticagrelor or prasugrel treatment. TG, platelet reactivity and EPCs were evaluated prior to P2Y12 inhibitor loading dose (T0), and one day following (T1). RESULTS: Between December 2018 - July 2021, 83 consecutive STEMI patients were randomized to ticagrelor (N = 42) or prasugrel (N = 41) treatment. No differences were observed at T0 for all measurements. P2Y12 reactivity units (PRU) at T1 did not differ as well (prasugrel 13.2 [5.5-20.8] vs. ticagrelor 15.8 [4.0-26.3], p = 0.40). At T1, prasugrel was a significantly more potent TG inhibitor, with longer lag time to TG initiation (7.7 ± 7.5 vs. 3.9 ± 2.1 min, p < 0.01), longer time to peak (14.1 ± 12.6 vs. 8.3 ± 9.7 min, p = 0.03) and a lower endogenous thrombin potential (AUC 2186.1 ± 1123.1 vs. 3362.5 ± 2108.5 nM, p < 0.01). Furthermore, EPCs measured by percentage of cells expressing CD34 (2.6 ± 4.1 vs. 1.1 ± 1.1, p = 0.01) and CD133 (2.3 ± 1.8 vs. 1.4 ± 1.5, p = 0.01) and number of colony forming units (CFU, 2.1 ± 1.5 vs. 1.1 ± 1.0, p < 0.01) were significantly higher in the prasugrel group. CONCLUSION: Among STEMI patients, prasugrel as compared to ticagrelor was associated with more potent TG inhibition and improved EPCs count and function.
Subject(s)
Endothelial Progenitor Cells , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Ticagrelor/therapeutic use , Prasugrel Hydrochloride/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , ST Elevation Myocardial Infarction/drug therapy , Thrombin , Purinergic P2Y Receptor Antagonists/therapeutic use , Adenosine/therapeutic use , Treatment Outcome , Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effectsABSTRACT
BACKGROUND: The optimal antithrombotic treatment for patients with atrial fibrillation (AF) that undergo percutaneous coronary intervention (PCI) is controversial. Dual therapy (clopidogrel and a direct oral anticoagulant [DOAC]) is safer than triple therapy (warfarin, aspirin, and clopidogrel), while efficacy is unclear. We aimed to evaluate thrombin generation (TG) under dual and triple therapy. METHODS: A noninterventional prospective trial in patients with AF undergoing PCI. Patients received 4 weeks of triple therapy with aspirin, clopidogrel, and a DOAC followed by aspirin withdrawal. TG was measured in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) at 3 five to 21 points, day 1 after PCI (TIME 0), 4 weeks after PCI (TIME 1), and 2 weeks after aspirin withdrawal (TIME 2). RESULTS: Twenty-three patients (18 men, median age 78 years, 83% with acute coronary syndrome) were included. Endogenous thrombin potential (ETP) in PPP was high at TIME 0 compared with TIME 1 (ETP 3,178 ± 248 nM vs. 2,378 ± 222 nM, p = 0.005). These results remained consistent when measured in PRP. No significant difference in ETP was found before (TIME 1) and after aspirin withdrawal (TIME 2) although few patients had high ETP levels after stopping aspirin. CONCLUSIONS: TG potential is high immediately after PCI and decreases 4 weeks after PCI in patients receiving triple therapy. TG remains constant after aspirin withdrawal in most patients, suggesting that after 1 month the antithrombotic effect of dual therapy may be similar to triple therapy.
