title: [Impact of pharmacogenetic testing on the risk of bleedings and excessive hypocoagulation episodes in the use of warfarin: the first meta-analysis of Russian prospective studies].
abstract: OBJECTIVE
  To perform a meta-analysis of Russian prospective studies comparing the pharmacogenetic versus conventional warfarin dosing procedures.
  
  
  METHODS
  Publications were sought in the PubMed and eLibrary through September 30, 2013. Seven prospective studies comparing the pharmacogenetic method of warfarin dosing with consideration for CYP2C9, VKORC1, and CYP4F2 gene polymorphisms with the conventional one were selected. The number of minor and major bleedings and hypocoagulation episodes was taken into account. The meta-analysis was performed using MIX Pro 2.0.
  
  
  RESULTS
  Six studies compared the number of bleedings in experimental and control groups. Analysis of statistical heterogeneity showed that extraneous factors did not influence the results of meta-analysis. The pharmacogenetic approach decreases the risk of bleeding. The pooled odds ratio (OR) was significant for minor (OR = 0.49; 95% confidence interval (CI), 0.31 to 0.78; p = 0.002), major (OR = 0.07; 95% CI, 0.008 to 0.54; p = 0.01) and both minor and major bleedings (OR = 0.49; 95% CI, 0.31 to 0.78; p = 0.002). Six studies estimated the number of hypocoagulation cases. There was no evidence for statistical heterogeneity (Q-test p = 0.13; I2 = 40%). Four studies showed a group difference in the number of hypocoagulation cases (p < 0.05). The pooled OR was 0.21 (95% CI, 0.15 to 0.3; p < 0.01). The pharmacogenetic dosing groups had fewer hypocoagulation episodes than the control ones.
  
  
  CONCLUSIONS
  The pharmacogenetic approach decreases the risk of bleeding and the episodes of hypocoagulation. The performed meta-analysis covered only two randomized trials. Improving the metalogic quality and statistical power of Russian studies will be able to get more reliable data on the impact of pharmacogenetic testing on clinical outcomes during warfarin therapy.
authors.forename: D A
authors.initials: DA
authors.lastname: Sychev
authors.forename: D V
authors.initials: DV
authors.lastname: Ivashchenko
authors.forename: I V
authors.initials: IV
authors.lastname: Rusin
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001778:Blood Coagulation Disorders / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D002986:Clinical Trials as Topic; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods*; D011446:Prospective Studies; D012426:Russia; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin