TY - JOUR
T1 - Vorapaxar and optimal aspirin dose
T2 - The FDA outlook
AU - Serebruany, Victor L.
AU - Fortmann, Seth D.
AU - Kim, Moo Hyun
PY - 2016/1/15
Y1 - 2016/1/15
N2 - 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.
AB - 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.
KW - Aspirin
KW - Bleeding
KW - Clinical trials
KW - Efficacy
KW - Vorapaxar
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U2 - 10.1016/j.ijcard.2015.11.064
DO - 10.1016/j.ijcard.2015.11.064
M3 - Article
C2 - 26609688
AN - SCOPUS:84952690604
VL - 203
SP - 903
EP - 905
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
ER -