title: Vorapaxar and optimal aspirin dose: The FDA outlook.
abstract: Vorapaxar, a novel thrombin PAR-1 inhibitor, approved for post-myocardial infarction, and peripheral artery disease indications has been tested in 2 major clinical trials. In the successful TRA2P, antecedent aspirin (ASA) has been used in 94% of patients, and in failed TRACER in over 96% of patients. However, both trial publications were silent on the impact of ASA dose on clinical outcomes after voraparax. We determined which ASA dose range should be used in combination with voraparax based on the TRA2P and TRACER secondary FDA review. The data suggest that for both voraparax trials, younger patients, males, and diabetics received higher ASA doses. The interactions between voraparax efficacy and ASA dose ≥ 300 mg was marginally significant by Cox regressions for TRA2P (CI=1.00-1.61; p=0.048) and strongly trended in TRACER (CI=0.98-1.47; p=0.073). Bleeding rates were overall slightly higher with voraparax than with placebo, and were the highest in patients receiving ASA dosages ≥ 300 mg. However, there were no interactions between ASA dose and GUSTO moderate/severe bleeding. In conclusion, the efficacy of voraparax in TRA2P and TRACER, was slightly worse while bleeding was substantially worse with the higher over 300 mg/day of ASA dosages. Voraparax label should recommend ASA daily use in 75 to 100mg range for concomitant use.
authors.affiliation: HeartDrug™ Research Laboratories, Johns Hopkins University, Osler Medical Building, 7600 Osler Drive, Suite 307, Towson, Maryland 21204, United States. Electronic address: vserebr1@jhmi.edu.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
authors.affiliation: HeartDrug™ Research Laboratories, Johns Hopkins University, Osler Medical Building, 7600 Osler Drive, Suite 307, Towson, Maryland 21204, United States.
authors.forename: Seth D
authors.initials: SD
authors.lastname: Fortmann
authors.affiliation: Department of Cardiology, Dong-A University, Busan, Republic of Korea. Electronic address: kimmh@dau.ac.kr.
authors.forename: Moo Hyun
authors.initials: MH
authors.lastname: Kim
mesh_terms: D001241:Aspirin / Q000008:administration & dosage*; D017277:Drug Approval / Q000379:methods*; D006801:Humans; D007783:Lactones / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage*; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D018179:Receptors, Thrombin; D001241:Aspirin; C530299:vorapaxar
keywords: Aspirin; Bleeding; Clinical trials; Efficacy; Vorapaxar