Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin

Dahal, Khagendra; Sharma, Sharan Prakash; Fung, Erik; Lee, Juyong; Moore, Jason H.; Unterborn, John; Williams, Scott M.

doi:10.1378/chest.14-2947

Cited by 27 publications

(21 citation statements)

References 59 publications

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“…Results demonstrated that GD algorithm significantly shortened time to first therapeutic INR and time to reach stable therapeutic dose, and reduced the risk of warfarin‐related major bleedings. GD algorithm presented similar PTTR at ≤1 month and higher PTTR at >1 month follow‐up compared to CD method, which is in accordance with the finding of previous meta‐analyses . There was no significant difference in the incidence of patients achieving stable dose between GD and CD groups at ≤1 month follow‐up, but more patients in the GD group achieving stable dose at >1 month follow‐up.…”

Section: Discussionsupporting

confidence: 89%

“…On the contrary, the Clarification of Optimal Anticoagulation through Genetics (COAG) trial of 1,015 patients did not illustrate better INR control with genotype‐guided warfarin dosing. There were also several meta‐analyses assessing the clinical benefits of genotype‐guided regimen for warfarin dosing, and their conclusions were also discrepant. Controversy about effectiveness of GD for warfarin challenged decision makers to decide whether it is reasonable to introduce it into clinical practice.…”

Section: What Is Known and Objectivementioning

confidence: 99%

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Genotype-guided dosing versus conventional dosing of warfarin: A meta-analysis of 15 randomized controlled trials

et al. 2018

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Summary What is known and Objective Genotype‐guided warfarin dosing algorithm is designed to predict the initial and stable dose of warfarin. However, whether this strategy is superior to conventional dosing method has not been consistently proven. To determine the benefit of genotype‐guided dosing vs conventional dosing of warfarin, we performed a meta‐analysis. Methods Literature was searched in PubMed, Embase and Central for published studies, and in clinicaltrials.gov for unpublished studies. Randomized controlled trials (RCTs) comparing genotype‐guided dosing with conventional dosing of warfarin were included in the meta‐analysis. Risk of bias of eligible RCTs was assessed with the Cochrane Collaboration's tool. Meta‐analysis was conducted by STATA software. The reliability of currently available evidence was determined with TSA software. Results and Discussion Fifteen RCTs with a total of 4852 patients were identified for the meta‐analysis. Genotype‐guided dosing of warfarin was associated with higher percentage time within therapeutic range (PTTR) and more patients achieving stable dose at >1 month follow‐up, shorter time to first therapeutic international normalized ratio (INR), shorter time to stable therapeutic dose, and decreased risk of warfarin‐related major bleeding events compared with conventional dosing. However, there were no statistically significant differences in PTTR and incidence of patients achieving stable dose within 1 month, INR >4, all bleeding events, thromboembolism and all‐cause mortality. What is new and Conclusion Genotype‐guided dosing should be considered in patients initiating warfarin treatment, especially in those with a history of haemorrhage. However, further studies are still needed to determine the cost‐effectiveness of routine warfarin‐related genotypes testing.

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Section: Discussionsupporting

confidence: 89%

Section: What Is Known and Objectivementioning

confidence: 99%

Genotype-guided dosing versus conventional dosing of warfarin: A meta-analysis of 15 randomized controlled trials

et al. 2018

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“…Pharmacoeconomic studies have suggested a growing improvement in cost‐effectiveness. A meta‐analysis of major RCTs comparing pharmacogenetic guided dosing to standard dosing showed an improvement of TTR by 6% and a reduction in the risk of major bleeding by 66% . The European Pharmacogenetics of Anticoagulant Therapy, an ongoing RCT, uses a bedside test that can provide results to guide therapy within 1.5 hours .…”

Section: Future Directionsmentioning

confidence: 99%

Warfarin Pharmacogenomics in Diverse Populations

et al. 2017

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Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African Americans and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarinrelated adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype-guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry. Despite differing frequencies of variants by race/ethnicity, most evidence in diverse populations evaluates variants that are most common in populations of European ancestry. Algorithms that do not include variants important across race/ethnic groups are unlikely to benefit diverse populations. In some race/ethnic groups, development of race-specific or admixture-based algorithms may facilitate improved genotype-guided warfarin dosing algorithms above and beyond that seen in individuals of European ancestry. These observations should be considered in the interpretation of literature evaluating the clinical utility of genotype-guided warfarin dosing. Careful consideration of race/ethnicity and additional evidence focused on improving warfarin dosing algorithms across race/ethnic groups will be necessary for successful clinical implementation of warfarin pharmacogenomics. The evidence for warfarin pharmacogenomics has a broad significance for pharmacogenomic testing, emphasizing the consideration of race/ethnicity in discovery of gene-drug pairs and development of clinical recommendations for pharmacogenetic testing.

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“…To optimize anticoagulation control, the use of genetic‐based algorithms, collectively termed ‘genotype‐guided dosing’, has been devised. However, previously published randomized controlled trials (RCTs) comparing the effects of genotype‐guided dosing against conventional dosing (either fixed dosing or clinically guided dosing) strategies , and even their subsequent meta‐analyses, have yielded conflicting results . A meta‐analysis published in 2015, which pooled the evidence from 11 RCTs with trial sequential analysis , reported a shorter time to reach the first therapeutic or stable international normalized ratio (INR), and improvements in markers of anticoagulation control such as the time in therapeutic range (TTR) and the number of patients with an out‐of‐range INR, although this did not translate into better clinical outcomes of reducing bleeding, thromboembolism or mortality.…”

Section: Introductionmentioning

confidence: 99%

Genotype‐guided warfarin dosing vs. conventional dosing strategies: a systematic review and meta‐analysis of randomized controlled trials

Tse

Gong

et al. 2018

Brit J Clinical Pharma

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Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin

Cited by 27 publications

References 59 publications

Genotype-guided dosing versus conventional dosing of warfarin: A meta-analysis of 15 randomized controlled trials

Genotype-guided dosing versus conventional dosing of warfarin: A meta-analysis of 15 randomized controlled trials

Warfarin Pharmacogenomics in Diverse Populations

Genotype‐guided warfarin dosing vs. conventional dosing strategies: a systematic review and meta‐analysis of randomized controlled trials

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