Table 1.

Drugs acting on PAR signaling.

DRUG CLASS [references]	CLINICALLY AVAILABLE MOLECULES	MECHANISM	CLINICAL USE	ROLE IN AF
Heparins (Spronk, 2017)	Unfractionated heparins, low molecular weight heparins	Fxa and thrombin inhibition by binding to anti-thrombins	Parenteral anticoagulants	Reduced atrial fibrosis
Heparin derivatives (Spronk, 2017)	Fondaparinux (penta-saccharide)	FXa inhibition	Parenteral anticoagulant	Reduced atrial fibrosis
Direct thrombin inhibitors(Chang, 2012; Jumeau, 2016; Altieri, 2018a)	Dabigatran, ximelagatran	Thrombin inhibition	(New) oral anticoagulants	Lower atrial fibrosis, inflammation, AF inducibility
Factor Xa inhibitors(Chang, 2012; Bukowska, 2013; Font, 2018; Kondo, 2018)	Apixaban, rivaroxaban, edoxaban	Reduction of thrombin formation	(New) oral anticoagulants	Lower atrial fibrosis, inflammation, firing of pulmonary veins, AF inducibility
PAR-1 inhibitors (Chang, 2012; Tricoci, 2012; Bonaca, 2014; Magnani, 2015; Jumeau, 2016; Chang, 2018; Schoergenhofer, 2018; Ungar, 2018; Friebel, 2019)	Vorapaxar	Block of PAR-1 signaling	Oral anti-platelet agent	Unknown
DPP-4 inhibitors (Lendeckel, 2001; Tremblay, 2014; Wronkowitz, 2014; Gong et al., 2015; Yamamoto, 2015; Chang, 2017; Zhang, 2017; Igarashi, 2018)	Sitagliptin, saxagliptin and other gliptins	Inhibition of circulating and local DPP-4, a PAR activator	Type-II diabetes (oral glucose lowering)	Reduced inflammation, small evidence
Chymase inhibitors (Matsumoto, 2003; Hooshdaran, 2017)	None	Inhibition of local chymases, PAR-1 activators	Experimental drugs	Unknown