title: Antiplatelet Effect Durability of a Novel, 24-Hour, Extended-Release Prescription Formulation of Acetylsalicylic Acid in Patients With Type 2 Diabetes Mellitus.
abstract: High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162.5 mg/day for 14 ± 4 days. Multiple platelet function tests, serum and urinary thromboxane B2metabolites, prostacyclin metabolite, and high-sensitive C-reactive protein levels were assessed at 1, 12, 16, and 24 hours post-dose. Patients with high platelet turnover and/or high platelet reactivity were treated with ER-ASA 325 mg/day for 14 ± 4 days, and laboratory analyses were repeated. All patients responded to ER-ASA 162.5 mg/day as measured by arachidonic acid-induced aggregation, and there was no loss of the platelet inhibitory effect of ER-ASA 162.5 mg/day over 24 hours post-dose (p = not significant). The antiplatelet effect was sustained over 24 hours for all platelet function measurements. Mean 1- to 24-hour serum thromboxane B2levels were low with both doses and were lower with ER-ASA 325 mg/day compared with 162.5 mg/day therapy (p = 0.002). In conclusion, ER-ASA 162.5 mg daily dose provided sustained antiplatelet effects over 24 hours in patients with type 2 DM and multiple cardiovascular risk factors and had a favorable tolerability profile.
authors: Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, Virginia. Electronic address: paul.gurbel@inova.org.
authors: Paul A
authors: PA
authors: Gurbel
authors: Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, Virginia.
authors: Kevin P
authors: KP
authors: Bliden
authors: Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, Virginia.
authors: Rahul
authors: R
authors: Chaudhary
authors: New Haven Pharmaceuticals, Inc., North Haven, Connecticut.
authors: Jeff
authors: J
authors: Patrick
authors: Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, Virginia; Department of Neurology, Beijing Hospital, Beijing, China.
authors: Fang
authors: F
authors: Liu
authors: Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, Virginia; Department of Cardiology, China-Japan Friendship Hospital, Beijing, China.
authors: Gailing
authors: G
authors: Chen
authors: Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, Virginia.
authors: Christopher
authors: C
authors: McLeod
authors: Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, Virginia.
authors: Udaya S
authors: US
authors: Tantry
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D011464:Epoprostenol / Q000096:biosynthesis / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008365:Manometry; D063847:Mean Platelet Volume; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000150:complications / Q000188:drug therapy*; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D013916:Thrombelastography; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D014664:Vasodilation
chemical_list: D003692:Delayed-Action Preparations; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D002097:C-Reactive Protein; D011464:Epoprostenol; D001241:Aspirin