title: Pharmacogenetics-Based versus Conventional Dosing of Warfarin: A Meta-Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Recently, using the patient's genotype to guide warfarin dosing has gained interest; however, whether pharmacogenetics-based dosing (PD) improves clinical outcomes compared to conventional dosing (CD) remains unclear. Thus, we performed a meta-analysis to evaluate these two strategies.
  
  
  METHODS
  The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese VIP and Chinese Wan-fang databases were searched. The Cochrane Collaboration's tool was used to assess the risk of bias in randomized controlled trials (RCTs). The primary outcome was time within the therapeutic range (TTR); the secondary end points were the time to maintenance dose and time to first therapeutic international normalized ratio (INR), an INR greater than 4, adverse events, major bleeding, thromboembolism and death from any cause.
  
  
  RESULTS
  A total of 11 trials involving 2,678 patients were included in our meta-analysis. The results showed that PD did not improve the TTR compared to CD, although PD significantly shortened the time to maintenance dose (MD = -8.80; 95% CI: -11.99 to -5.60; P<0.00001) and the time to first therapeutic INR (MD = -2.80; 95% CI: -3.45 to -2.15; P<0.00001). Additionally, PD significantly reduced the risk of adverse events (RR = 0.86; 95% CI: 0.75 to 0.99; P = 0.03) and major bleeding (RR = 0.36; 95% CI: 0.15 to 0.89, P = 0.03), although it did not reduce the percentage of INR greater than 4, the risk of thromboembolic events and death from any cause. Subgroup analysis showed that PD resulted in a better improvement in the endpoints of TTR and over-anticoagulation at a fixed initial dosage rather than a non-fixed initial dosage.
  
  
  CONCLUSIONS
  The use of genotype testing in the management of warfarin anticoagulation was associated with significant improvements in INR-related and clinical outcomes. Thus, genotype-based regimens can be considered a reliable and accurate method to determine warfarin dosing and may be preferred over fixed-dose regimens.
  Database registration: CRD42015024127.
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China.|Department of Clinical Pharmacology, Hangzhou Translational Medicine Research Center, Hangzhou, Zhejiang Province, China.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China.|Department of Clinical Pharmacology, Hangzhou Translational Medicine Research Center, Hangzhou, Zhejiang Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China.|Department of Clinical Pharmacology, Hangzhou Translational Medicine Research Center, Hangzhou, Zhejiang Province, China.|Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China.|The first Affiliated Hangzhou Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.
authors.forename: Nengming
authors.initials: N
authors.lastname: Lin
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D010597:Pharmacogenetics; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D013923:Thromboembolism / Q000188:drug therapy / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014859:Warfarin