title: Comparison of rivaroxaban mono-therapy and standard-therapy adjusted by CYP2C9 and VKORC1 genotypes in symptomatic pulmonary embolism.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Linli
authors.initials: L
authors.lastname: Duan
authors.affiliation: 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.
authors.forename: Nuofu
authors.initials: N
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Huang
authors.initials: H
authors.lastname: Yan
authors.affiliation: 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.
authors.forename: Yehui
authors.initials: Y
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hong
authors.affiliation: 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.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Su
authors.affiliation: 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.
authors.forename: Rongchang
authors.initials: R
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.affiliation: 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.
authors.forename: Chunli
authors.initials: C
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D017984:Enoxaparin / Q000008:administration & dosage / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000235:genetics; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000627:therapeutic use*; D020246:Venous Thrombosis / Q000188:drug therapy / Q000235:genetics; D014812:Vitamin K / Q000037:antagonists & inhibitors; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D014812:Vitamin K; D000069552:Rivaroxaban; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: CYP2C9; Deep venous thrombosis; Pulmonary embolism; Rivaroxaban; VKORC1