TAILOR- Thrombocytes And IndividuaLization of ORal antiplatelet therapy in percutaneous coronary intervention

Abstract

Background and objectives: Clopidogrel low-response (CLR) has been linked to adverse clinical events and individualization of antiplatelet therapy according to platelet function monitoring has become possible. We aimed at investigating the antiplatelet effect and safety of standard-dose prasugrel compared to doubledose clopidogrel in patients presenting with stable coronary disease or acute coronary syndromes and exhibiting high on-treatment platelet reactivity (HTPR) at baseline. Methods: Platelet reactivity was assessed with multiple electrode aggregometry (MEA) in patients with ischemic heart disease undergoing cardiac catheterization. The cut-off for response to clopidogrel was set to 70 Multiplate-ADP Units with low-response defined as MEA-values>70 U. Of the 923 screened, 237 (25.7%) exhibited CLR and 106 patients were randomized to an intensified antiplatelet regimen for one month: 52 were assigned to double-maintenance dose clopidogrel and 54 were assigned to standard dose prasugrel. The remaining 131 patients with HTPR were excluded mainly due to contraints to prasugrel use and served instead as controls. Results: HTPR was less pronounced in stable angina patients. The prevalence of diabetes was greater in the clopidogrel low-response population compared to patients with normal platelet reactivity. (30.8% vs 23.9%, p=0.039) Intensifying antiplatelet therapy improved platelet inhibition in 73.1% of all randomized patients. Prasugrel entailed a much greater platelet inhibition (54U ±24 versus 61U ±24 for clopidogrel, p=0.02) and a lower rate of poor response at follow-up compared to double maintenance-dose clopidogrel (20.4% of HTPR in the prasugrel-versus 42% in the clopidogrel arm, p=0.02). No major bleeds were observed during follow-up. In the control group with no intervention (n=131), we observed 3 cases of cardiovascular deaths within 30 days following the index procedure, while no case of fatal outcome was reported in the randomized group. Conclusion: Tailored antiplatelet therapy in patients exhibiting Clopidogrel low-response prior to percutaneous coronary intervention proved to efficiently reduce platelet activity. Prasugrel demonstrated a greater reduction in platelet aggregation compared to double-dose clopidogrel and also a greater reduction in the rate of HTPR at follow-up. Both regimens were well tolerated and no cases of adverse clinical events were reported in the randomized group.