title: Targeting thrombin long-term after an acute coronary syndrome: Opportunities and challenges.
abstract: Patients after an acute coronary syndrome (ACS) are at increased risk of recurrent thrombotic events, justifying the search for additional antithrombotic treatments. The pathophysiology of ACS involves arterial thrombus formation, in turn occurring because of a combination of platelet activation and fibrin formation, with thrombin playing a key role in both. Antiplatelet therapy, targeting the thromboxane pathway and the ADP P2Y12 receptor has been widely accepted for secondary prevention after an ACS. Now, data from recent clinical trials in such patients also encourage the pursuit of inhibiting thrombin formation or thrombin-mediated platelet activation in addition to antiplatelet therapy. This "triple pathway inhibition", including inhibition of thrombin activity or thrombin receptor(s), is currently an option in pure ACS, but already a must in the setting of ACS accompanied by atrial fibrillation (AF), where anticoagulants have been shown to be much more effective than antiplatelet agents in preventing stroke. We here discuss the challenges of managing combined thrombin activity or receptor inhibition and antiplatelet therapy in all such patients. Translating this into practice still requires further studies and patient tailoring to fully exploit its potential.
authors.affiliation: Institute of Cardiology and Center of Excellence on Aging, G. d'Annunzio University - Chieti-Pescara, Pisa, Italy; G. Monasterio Foundation, Pisa, Italy. Electronic address: rdecater@unich.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Department of Medicine (Cardiology), Tokai University School of Medicine, Isehara, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D000991:Antithrombins / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D004359:Drug Therapy, Combination; D006801:Humans; D058990:Molecular Targeted Therapy; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D044463:Receptor, PAR-1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000991:Antithrombins; D010975:Platelet Aggregation Inhibitors; D044463:Receptor, PAR-1; D013917:Thrombin
keywords: Acute coronary syndromes; Anticoagulants; Atherosclerosis; Atherothrombosis; Coagulation; Myocardial infarction; Non-vitamin K antagonist oral anticoagulants; Platelets; Thrombin; Thrombosis