Vorapaxar and optimal aspirin dose: The FDA outlook

• Published in: International journal of cardiology Vol. 203; pp. 903 - 905
• Main Authors: Serebruany, Victor L, Fortmann, Seth D, Kim, Moo Hyun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 15-01-2016
• Subjects: Aspirin; Aspirin - administration & dosage; Bleeding; Cardiovascular; Clinical trials; Drug Approval - methods; Efficacy; Humans; Lactones - administration & dosage; Platelet Aggregation Inhibitors - administration & dosage; Pyridines - administration & dosage; Receptors, Thrombin - antagonists & inhibitors; United States; United States Food and Drug Administration; Vorapaxar; Clinical trials; Efficacy; Aspirin; Vorapaxar; Bleeding
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2015.11.064

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 100 mg range for concomitant use.