Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial

Gage, Brian F.; Bass, Anne R.; Lin, Hsin-Chang; Woller, Scott C.; Stevens, Suzanne; Al-Hammadi, Noor

doi:10.1016/j.jvsv.2017.10.005

Cited by 54 publications

(101 citation statements)

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“…As presented in the flow chart of detailed selection process (Figure ), a total of 1604 citations were identified from literature search, of which 15 RCTs with a total of 4852 patients were included in the meta‐analysis. The characteristics of 15 eligible studies are summarized in Table .…”

Section: Resultsmentioning

confidence: 99%

“…The characteristics of 15 eligible studies are summarized in Table . The locations of the trials distributed in five countries: the United States (7 trials), China (6 trials), Italy (1 trial), UK (1 trial) and Sweden (1 trial). Study population included patients taking warfarin for atrial fibrillation/flutter, venous thromboembolism, pulmonary embolism, prosthetic valve, prosthetic joint and stroke.…”

Section: Resultsmentioning

confidence: 99%

“…However, randomized controlled trials (RCTs) comparing GD with conventional dosing (CD) of warfarin have shown inconsistent results. Two large high‐quality multicenter trials, the European Pharmacogenetics of Anticoagulant Therapy (EU‐PACT) trial and the Genetic Informatics Trial (GIFT), found improvement in percentage time within therapeutic range (PTTR) of international normalized ratio (INR). 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.…”

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: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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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“…Applying patient‐specific data and pharmacogenomics prior to the use of many common medications such as anticoagulants and antidepressants has been shown to improve efficacy, safety, and/or therapeutic outcomes in targeted patient populations . Pharmacogenomic data can also be beneficial when used within an existing treatment regimen to guide medication dosage/selection of alternative treatment regimens in at‐risk patients (eg, those experiencing adverse effects or lack of response to proven therapies).…”

Section: Perspectives On Precision Medicine By Prnmentioning

confidence: 99%

PRN OPINION PAPER: Application of precision medicine across pharmacy specialty areas

Caudle

Gammal

Karnes

et al. 2019

J Am Coll Clin Pharm

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Clinical pharmacists have been incorporating precision medicine into practice for decades. Drug selection and dosing based on patient‐specific clinical factors such as age, weight, renal function, drug interactions, plasma drug concentrations, and diet are expected as part of routine clinical practice. Newer concepts of precision medicine such as pharmacogenomics have recently been implemented into clinical care, while other concepts such as epigenetics and pharmacomicrobiomics still predominantly exist in the research area but clinical translation is expected in the future. The purpose of this paper is to describe current and emerging aspects of precision medicine as it relates to clinical pharmacy across a variety of specialty areas of practice, with perspectives from the American College of Clinical Pharmacy Practice and Research Network membership.

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“…Dosing warfarin can prove challenging after surgery due to the metabolic response to surgery, and an interesting development is genotype-guided dosing after hip or knee arthroplasty to reduce the risk of bleeding, venous thromboembolism and death 97. When bridging anticoagulation is indicated, the last dose of LMWH should be given 24 hours prior to the procedure and restarted 48 hours after the procedure 33.…”

Section: Postoperativementioning

confidence: 99%

Blood management in total knee arthroplasty: state-of-the-art review

et al. 2018

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Total blood loss from primary total knee arthroplasty may exceed 2 L with greater blood loss during revision procedures. Blood loss and allogeneic transfusion are strongly associated with adverse outcomes from surgery including postoperative mortality, thromboembolic events and infection. Strategies to reduce blood loss and transfusion rates improve patient outcomes and reduce healthcare costs. Interventions are employed preoperatively, intraoperatively and postoperatively. The strongest predictor for allogeneic blood transfusion is preoperative anaemia. Over 35% of patients are anaemic when scheduled for primary and revision knee arthroplasty, defined as haemoglobin <130 g/L for men and women, and the majority of cases are secondary to iron deficiency. Early identification and treatment of anaemia can reduce postoperative transfusions and complications. Anticoagulation must be carefully managed perioperatively to balance the risk of thromboembolic event versus the risk of haemorrhage. Intraoperatively, tranexamic acid reduces blood loss and is recommended for all knee arthroplasty surgery; however, the optimal route, dose or timing of administration remains uncertain. Cell salvage is a valuable adjunct to surgery with significant expected blood loss, such as revision knee arthroplasty. Autologous blood donation is not recommended in routine care, sealants may be beneficial in select cases but further evidence of benefit is required, and the use of a tourniquet remains at the discretion of the surgeon. Postoperatively, restrictive transfusion protocols should be followed with a transfusion threshold haemoglobin of 70 g/L, except in the presence of acute coronary syndrome. Recent studies report no allogeneic transfusions after primary knee arthroplasty surgery after employing blood conservation strategies. The current challenge is to select and integrate different blood conserving interventions to deliver an optimal patient pathway with a multidisciplinary approach.

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Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial

Cited by 54 publications

References 0 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

PRN OPINION PAPER: Application of precision medicine across pharmacy specialty areas

Blood management in total knee arthroplasty: state-of-the-art review

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