Rivaroxaban and Adjusted-Dose Warfarin Based on VKORC1 and CYP2C9 Genotypes for the Treatment of Symptomatic Pulmonary Embolism in Real World

Abstract

SESSION TITLE: Pulmonary Vascular Disease: VTE SESSION TYPE: Original Investigation Poster PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM PURPOSE: To compare the efficacy and safety of rivaroxaban and warfarin in treatment of pulmonary embolism (PE) and evaluate the clinical significance of the genotypes of VKORC1 and CYP2C9 in adjusted dose warfarin. METHODS: A total of 62 patients who had acute symptomatic PE with or without deep vein thrombosis (DVT) were randomized to receive rivaroxaban (n=30) (15 mg twice daily for 3 weeks, followed by 20 mg once daily last for the third months, then 10mg daily continued to the sixth months) or standard therapy of enoxaparin overlapping with and followed by an adjusted-dose warfarin (n=32) for 3 or 6 months. Meanwhile, the patients who receive warfarin were detected the genotypes of VKORC1 and CYP2C9. The primary efficacy outcome was recurrence and vanishing absorption of PE from imaging examination at the first month, third or sixth months. The principal safety outcome was major or non-major clinically relevant bleeding and other adverse events. RESULTS: There were no significant difference of primary efficacy outcome between rivaroxaban and standard therapy, whether at the first month (X2=2.848 P=0.416) or third and sixth months (X2=3.263 P=0.353). However, the length of hospital stay, rivaroxaban (9.29±3.70) was significantly less than standard therapy (11.38±3.12) (t=2.37 P=0.021). The non-major clinically relevant bleeding occurred in 5 (16.7%) patients in the rivaroxaban and in 16 (50%) patients in the standard therapy (t=7.681 P=0.006). Major bleeding was observed in no patients in rivaroxaban while in 2 (6.3%) patients in standard therapy. Other adverse events including 1 (3.3%) stroke in rivaroxaban and 1 (3.1%) death in standard therapy which all can not rule out PE. There were significant difference between the recommended dosages (3.5±0.86) of VKORC1 and CYP2C9 compared the actual dose of warfarin at discharge (4.02±1.26) (P=0.042). CONCLUSIONS: In patients with acute symptomatic PE, rivaroxaban was as efficacious as standard therapy enoxaparin followed by warfarin, However, the length of hospital stay, non-major clinically relevant and Major bleeding were significantly lower than standard therapy. Adjusting dose of warfarin which according toVKORC1 and CYP2C9, can not reduce the incidence of bleeding. CLINICAL IMPLICATIONS: Rivaroxaban has a similar efficacy while a better bleeding profile to standard therapy of enoxaparin overlapping with and followed by warfarin, and our study support the use of rivaroxaban as a single oral agent for patients with PE. Detecting VKORC1 and CYP2C9 maybe has little clinical significance. DISCLOSURE: The following authors have nothing to disclose: Linli Duan, Nuofu Zhang, Chunli Liu No Product/Research Disclosure Information