To evaluate the efficacy and safety of genotype testing for dosing of warfarin.
We will identify relevant studies in any language by searching electronic databases from inception to March 2015. Databases to be searched will include PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese VIP database, Chinese Wan Fang database.
Types of study to be included
Condition or domain being studied
Warfarinis the most widely used oral anticoagulant for the treatment and prevention of thromboembolic events. It is difficult to determine accurate doses for warfarin owing to a narrow therapeutic window and substantial interindividual variation in dose-response. Insufficient anticoagulation increases the risk for thrombotic events, whereas overdosing confers a predisposition to bleeding. Several factors are associated with variation in warfarin dose requirements, including age, height, body weight, sex, race, dietary vitamin K intake and drug interactions. The focus of study over the last decade has shifted towards identifying genetic factors of dose requirements. It was reported that several genes might be related to the activity and metabolism of warfarin, with genotypes of the cytochrome-P450 gene (CYP) 2C9 and the vitamin K epoxide reductase complex subunit 1 gene (VKORC1) being the most important. These genotypes plus clinical characteristics predict approximately one half of interindividual dose variability. Several previous studies have raised interest in using the genetic variants of CYP2C9 and VKORC1 to guide warfarin dosing. However, it is unclear whether CYP2C9 and VKORC1 genotype-based warfarin dosing can truly improve clinical outcomes.
Inclusion Criteria: patients were at least 18 years old with an indication for anticoagulation.
Exclusion Criteria: patients with a history of treatment with warfarin and known maintenance dose.
Genetic-based warfarin dosing.
Non-genetic-based warfarin dosing.
Time within therapeutic range (TTR).
1. time to maintenance dose
2. time to first therapeutic INR
3. INR greater than 4
4. adverse events
5. major bleeding
7. all-cause mortality
Data extraction, (selection and coding)
Two reviewers will screen the titles and, when available, abstracts of all reports identified by the search strategies. All potentially relevant reports will be retrieved in full and assessed independently by two reviewers. Any disagreement will be resolved through discussion.
Risk of bias (quality) assessment
The methodological quality of the included studies will be assessed with the Cochrane Collaboration’s risk of bias tool. Two reviewers will independently assess the risk of bias within each included trial based on the following domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, other bias.
Strategy for data synthesis
For continuous data, we will use the mean difference (MD) when the pooled trial used the same rating scale to assess an outcome. For dichotomous data, the impact of the intervention will be expressed as relative risk (RR) with 95% CI will be calculated. Fixed effects or random effects will be used, depending on the existence of heterogeneity. Heterogeneity will be evaluated with I-squared calculations. When heterogeneity will be observed, a sensitivity analysis will be conducted. Statistical analysis will be performed with RevMan 5.3 with two tailed p-values <0.05 considered significant.
Analysis of subgroups or subsets
A subgroup analysis will be performed to assess whether pooled outcomes could vary by the type of conventional regimen (fixed-dose regimen or algorithm included clinical variables only)
Contact details for further information
Organisational affiliation of the review
Mr Changcheng Shi, Hangzhou First People’s Hospital Mrs Wei Yan, Hangzhou First People’s Hospital Mr Gang Wang, Hangzhou First People’s Hospital Mrs Fei Wang, Hangzhou First People’s Hospital Mrs Qingyu Li, Hangzhou First People’s Hospital Professor Nengming Lin, Hangzhou First People’s Hospital
Formal screening of search results against eligibility criteria
Risk of bias (quality) assessment
PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites.