In the case of vorapaxar, which is the only approved drug of a novel class antithrombotic agent acting on the protease-activated receptor-1 (PAR-1), trials directly assessing stroke management are lacking.4PAR-1 is fundamental for pleiotropy of coagulation factors in the central nervous system (CNS).5The main proteases that can activate PAR-1 are matrix metalloproteinase 9 (MMP-9)5and thrombin, whose activation state, concentration, and association with activated protein C (aPC) lead to differential pathway activation in physiology6as well as CNS pathologies. This evidence concerns the gene F2R and Stroke.