Linli Duan1, Nuofu Zhang1, Huang Yan1, Yehui Guo1, Cheng Hong1, Xinyan Yang1, Xiaofen Su1, Rongchang Chen1, Ying Zhou1, Nanshan Zhong1, Chunli Liu2. 1. Department of Respiration, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China; Guangzhou Institute of Respiratory Disease & State Key Laboratory of Respiratory Disease, Guangzhou 510120, China; National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China. 2. Department of Respiration, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China; Guangzhou Institute of Respiratory Disease & State Key Laboratory of Respiratory Disease, Guangzhou 510120, China; National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China. Electronic address: chunli.liu@aliyun.com.
Abstract
RATIONALE: Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism. Rivaroxaban is an oral anticoagulant, which directly inhibits Factor Xa. The objective of the current study was, in comparison to the standard-therapy method, to investigate the potential of rivaroxaban to improve the treatment of patients with PE, and to reduce hemorrhage in the standard-therapy group through adjusting the dose of warfarin by CYP2C9 and VKORC1 genotypes. METHODS:Sixty-two PE patients with or without deep venous thrombosis (DVT) was randomized to rivaroxaban mono-therapy or standard-therapy with enoxaparin followed by vitamin K antagonist (VKA). Concentration of the anticoagulants was adjusted according to the results of CYP2C9 and VKORC1 genotypes in order to stabilize the international normalized rate (INR) at 2.0-3.0 range. Length of hospital stay at initial hospitalization was compared, therapeutic efficacy was examined by computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion (V/Q) scan, and side-effect of anti-coagulants was monitored at 1-month, and 3- or 6-months follow-up check points. RESULTS: We found that, overall, patients who received rivaroxaban mono-therapy had a significantly shorter length of hospital stay compared with patients who received standard-therapy of enoxaparin followed by VKA (9.29±3.70 versus 11.38±3.12days, P=0.021). The therapeutic efficacy was of no marked difference between these two groups. However, after one month treatment, 50% (16/32) of the standard-therapy group had mild hemorrhage, which was significantly higher than that of rivaroxaban mono-therapy group (16.7%, 5/30, P=0.006). Moreover, a significantly higher rate in the standard-therapy group (22.2% versus 3.4%, P=0.032) was found after 3 or 6months therapy. Major bleeding was slightly but not significantly higher in the standard-therapy group than that in the rivaroxaban therapy group. In addition, 2 (6.3%) patients died from Life-threatening bleeding in the standard-therapy group. CONCLUSION: Findings of the current study suggested that rivaroxaban mono-therapy result in shorter hospital stay compared to the standard-therapy. Implication of CYP2C9 and VKORC1 genotypes in determining dose of warfarin, however, remains to be further examined in larger cohort studies.
RCT Entities:
RATIONALE: Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism. Rivaroxaban is an oral anticoagulant, which directly inhibits Factor Xa. The objective of the current study was, in comparison to the standard-therapy method, to investigate the potential of rivaroxaban to improve the treatment of patients with PE, and to reduce hemorrhage in the standard-therapy group through adjusting the dose of warfarin by CYP2C9 and VKORC1 genotypes. METHODS: Sixty-two PE patients with or without deep venous thrombosis (DVT) was randomized to rivaroxaban mono-therapy or standard-therapy with enoxaparin followed by vitamin K antagonist (VKA). Concentration of the anticoagulants was adjusted according to the results of CYP2C9 and VKORC1 genotypes in order to stabilize the international normalized rate (INR) at 2.0-3.0 range. Length of hospital stay at initial hospitalization was compared, therapeutic efficacy was examined by computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion (V/Q) scan, and side-effect of anti-coagulants was monitored at 1-month, and 3- or 6-months follow-up check points. RESULTS: We found that, overall, patients who received rivaroxaban mono-therapy had a significantly shorter length of hospital stay compared with patients who received standard-therapy of enoxaparin followed by VKA (9.29±3.70 versus 11.38±3.12days, P=0.021). The therapeutic efficacy was of no marked difference between these two groups. However, after one month treatment, 50% (16/32) of the standard-therapy group had mild hemorrhage, which was significantly higher than that of rivaroxaban mono-therapy group (16.7%, 5/30, P=0.006). Moreover, a significantly higher rate in the standard-therapy group (22.2% versus 3.4%, P=0.032) was found after 3 or 6months therapy. Major bleeding was slightly but not significantly higher in the standard-therapy group than that in the rivaroxaban therapy group. In addition, 2 (6.3%) patients died from Life-threatening bleeding in the standard-therapy group. CONCLUSION: Findings of the current study suggested that rivaroxaban mono-therapy result in shorter hospital stay compared to the standard-therapy. Implication of CYP2C9 and VKORC1 genotypes in determining dose of warfarin, however, remains to be further examined in larger cohort studies.