Clinical Application of Genotype-guided Dosing of Warfarin in Patients with Acute Stroke

Šupe, Svjetlana; Poljaković, Zdravka; Božina, Tamara; Ljevak, Josip; Šarinić, Viola Macolić; Božina, Nada

doi:10.1016/j.arcmed.2015.05.001

Cited by 17 publications

(21 citation statements)

References 44 publications

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“…In patients with acute stroke, genotypeguided dosing is recommended to be more useful by decreasing the time essential for stabilization when compared with fixed dosing. A priori and posteriori dosing could be estimated based on data about body weight, age, baseline, and target INR, with the option of considering the CYP2C9 and VKORC1 genotypes (a priori) and other information about previous doses and the INR (a posteriori), respectively (21,22).…”

Section: Resultsmentioning

confidence: 99%

“…The action of warfarin may constantly be inverted by vitamin K 1 , as the blood cannot be coagulated directly. After prescription, warfarin necessitates two to three days for onset of effective treatment in which the duration of the effect of a single dose is about two to five days (1)(2)(3)(4)(5)(6)(7)(14)(15)(16)(17)(18)(19)(20)(21)(22) Spontaneous spinal subdural hematoma is reported at a rare level in those receiving anticoagulant or antiplatelet agents (11). However, a great frequency of intracerebral hemorrhages with multiple cerebral microbleeds has been reported in warfarin-treated patients (12).…”

Section: Discussionmentioning

confidence: 99%

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Review of Warfarin; A Cytochrome P450 Metabolizing Drug, in Clinical Practice

Tolou-Ghamari

Mazdak

2016

Jentashapir J Health Res

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Context: For the prevention and management of thromboembolic complications, warfarin is the most extensively recommended anticoagulant. It is categorized as a drug with a narrow therapeutic window. Therefore, warfarin prescription requires special attention related to therapeutic drug monitoring.Evidence Acquisition: By categorizing the clinical implications of warfarin, this manuscript aims to provide a comprehensive (albeit somewhat brief) conclusion associated with its pharmacotherapy. The key words relevant to the topic were searched. Consequently, articles relevant to the pharmacotherapeutic management of warfarin were selected and reviewed in their entirety. Results:To obtain a reasonable level of stability between the required antithrombotic treatment and the risk of bleeding, an analysis of the literature revealed that the prothrombin time in terms of the international normalized ratio (INR) was found for each individual. The best model for stable warfarin dosage prediction was found to be based on multiple linear regression. Genotypeguided procedures were established to: 1, improve the time in the therapeutic range; 2, reduce time to the first therapeutic INR; and 3, reduce the time for the stable doses. Vitamin K epoxide reductase is an enzyme with an important role in vitamin K metabolism, and warfarin is metabolized in hepatocytes via a monooxygenase, cytochrome P450 2C9. In patients carrying 2C9*1/*2 and 2C9*2/*2 or 2C9*1/*3 alleles, the dose is recommended to be reduced by 18% -40% and 21% -49%, respectively. Conclusions:Race, age, body surface area, chronic kidney disease, CYP2C9*3 level, and VKORC1 variants could affect the dose of warfarin. To administer the proper doses of warfarin, patients and physicians might achieve the best results with the pharmacologist proficient anticoagulation database and recommended continuation program. Owing to its' unpredictability, caution must be taken when prescribing warfarin. More advanced warfarin pharmacotherapy studies are recommended based on a linear regression model specifically in the Iranian population.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Review of Warfarin; A Cytochrome P450 Metabolizing Drug, in Clinical Practice

Tolou-Ghamari

Mazdak

2016

Jentashapir J Health Res

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“…For instance, Shi et al and Wang et al extracted incorrect data for the endpoint of time to stable dose, and Tang et al categorized the control group of one study as fixed‐dose regimen by mistake. The latest meta‐analyses included 2 trials grouping patients by pseudo‐random, which could bring about great bias.…”

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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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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“…For instance, most of these drugs need to be intravenously injected, can cause serious side effects and usually have short half-life in the blood circulation. [26][27][28][29][30][31][32][33][34] To solve these problems, a series of nanopreparations, …”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of nanoscaled IQCA-TAVV as a delivery system capable of antiplatelet activation, targeting arterial thrombus and releasing IQCA

Zhu

Yang

et al. 2018

IJN

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Background Arterial thrombosis has been associated with a series of pathological conditions, and the discovery of arterial thrombosis inhibitor is of clinical importance. Methods By analyzing the pharmacophores of anti-platelet agents, thrombus targeting peptide and anti-thrombotic nano-systems 3S-1,2,3,4-tetrahydroisoquino-line-3-carbonyl-Thr-Ala-Arg-Gly-Asp(Val)-Val (IQCA-TAVV) was designed and prepared as a nano-scaled arterial thrombosis inhibitor. Results In vitro the nanoparticles of IQCA-TAVV were able to adhere onto the surface of activated platelets, attenuate activated platelets to extend pseudopodia and inhibit activated platelets to form aggregators. In vivo IQCA-TAVV targeted arterial thrombus, dose dependently inhibited arterial thrombosis with a 1 nmol/kg of minimal effective dose, and the activity waŝ1670 folds of that of aspirin. Conclusion IQCA-TAVV represented the design, preparation and application of nanomedicine capable of adhering on the surface of activated platelets, attenuating platelet activation, targeting arterial thrombus and inhibiting arterial thrombosis.

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Clinical Application of Genotype-guided Dosing of Warfarin in Patients with Acute Stroke

Cited by 17 publications

References 44 publications

Review of Warfarin; A Cytochrome P450 Metabolizing Drug, in Clinical Practice

Review of Warfarin; A Cytochrome P450 Metabolizing Drug, in Clinical Practice

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

Design and synthesis of nanoscaled IQCA-TAVV as a delivery system capable of antiplatelet activation, targeting arterial thrombus and releasing IQCA

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