CYP2C9 and VKORC1 genotyping for the quality of long-standing warfarin treatment in Russian patients

Panchenko, E. P.; Кропачева, Е. С.; Dobrovolsky, A. B.; Титаева, Е В; Zemlyanskaya, O A; Trofimov, Trofimov D.Yu.; Galkina, Irina P.; Лифшиц, Г. И.; Vereina, N. K.; Синицын, С. П.; Vorobyeva, N.A.; Grehova, Lyudmila; Zateyshchikov, Dmitry A.; Зотова, И. В.; Вавилова, Т. В.; Сироткина, О. В.; Grontkovskaya, Alevtina V.

doi:10.1038/s41397-020-0157-2

Cited by 8 publications

(9 citation statements)

References 45 publications

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“…Ten RCTs reported no statistically significant difference between the study groups in terms of bleeding complications. On the contrary, Panchenko et al [ 26 ] showed a higher percentage of major bleeding in the CG group than in the GG group ( p = 0.031). Li et al [ 20 ] demonstrated that the rate of bleeding and thrombosis was 0 in the GG group and 5 (17.2%) in the CG group ( p = 0.022).…”

Section: Resultsmentioning

confidence: 94%

“…Five out of eight RCTs showed a statistically significant lower TRSD in the GG group compared with the CG group [ 20 , 26 , 27 , 28 ]. Burmester et al showed a lower TRSD in the GG group than the CG group without reaching statistical significance [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

“…Of the 11 studies that measured TTR, 4 showed a significantly higher TTR in the GG group than in the CG group [ 1 , 22 , 27 , 31 ]. Four studies [ 23 , 25 , 26 , 28 ] reported a higher TTR in the GG group without finding statistical significance. Differently, Pengo et al [ 30 ] showed a superiority of the CG group, but also in this case, there was no statistical significance.…”

Section: Resultsmentioning

confidence: 99%

“…Nine and twelve studies evaluated the incidence of INR>4 and warfarin-related bleeding, respectively. Several RCTs [ 22 , 24 , 26 , 27 , 30 ] demonstrated a significant reduction in the incidence of INR>4 in the GG group. Four RCTs [ 21 , 28 , 29 , 31 ] showed that the compared groups were similar regarding %Time in INR>4.…”

Section: Resultsmentioning

confidence: 99%

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Opposite Response to Vitamin K Antagonists: A Report of Two Cases and Systematic Review of Literature

Conti

Manzo

Bellis

et al. 2022

JPM

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Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high response variability hamper their management. Several patients experience fluctuations in dose–response and are at increased risk of over- or under-anticoagulation. Therefore, it is essential to monitor the prothrombin time/international normalized ratio to determine the so-called stable dose and to adjust the dosage accordingly. Three polymorphisms, CYP2C9∗2, CYP2C9∗3 and VKORC1-1639G>A, are associated with increased sensitivity to VKAs. Other polymorphisms are associated with a request for a higher dose and VKA resistance. We described the clinical cases of two patients who were referred to the Clinical Pharmacology and Pharmacogenetics Unit of the University Hospital of Salerno for pharmacological counseling. One of them showed hypersensitivity and the other one was resistant to VKAs. A systematic review was performed to identify randomized clinical trials investigating the impact of pharmacogenetic testing on increased sensitivity and resistance to VKAs. Although international guidelines are available and information on the genotype-guided dosing approach has been included in VKA drug labels, VKA pharmacogenetic testing is not commonly required. The clinical cases and the results of the systematically reviewed RCTs demonstrate that the pharmacogenetic-based VKA dosing model represents a valuable resource for reducing VKA-associated adverse events.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Opposite Response to Vitamin K Antagonists: A Report of Two Cases and Systematic Review of Literature

Conti

Manzo

Bellis

et al. 2022

JPM

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“…We included 26 studies12‐37 encompassing 7898 patients in this systematic review and meta‐analysis (Figure 1). A low risk of bias was observed in most of the domains (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

A network meta‐analysis ofCYP2C9,CYP2C9withVKORC1andCYP2C9withVKORC1andCYP4F2genotype‐based warfarin dosing strategies compared to traditional

Sridharan

Sivaramakrishnan

2020

J Clin Pharm Ther

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What is known and objectives: Variations in genotypes were observed in randomized clinical trials (RCTs) that evaluated genotype-based warfarin dosing. We carried out a network meta-analysis to assess whether any clinically significant differences exist between RCTs evaluating CYP2C9 with VKORC1, with CYP2C9 alone and CYP2C9, VKORC1, with CYP4F2 dosing strategies.Methods: Electronic records were searched for RCTs comparing genotype-based warfarin with traditional-dosing strategies. Key outcomes included were the time to first therapeutic international normalized ratio (INR); time to stable INR or warfarin dose; percent time in therapeutic range (TTR); and the proportion of patients with supra-therapeutic INR. Weighted mean differences (WMD) and odds ratios (OR) with 95% confidence intervals (95% CI) were the effect estimates.Results and discussion: Twenty-six studies (7898 patients) were included. CYP2C9based warfarin dosing was associated with a shorter time to first therapeutic INR (WMD: -2.73, 95% CI: -3.41, -2.05) and stable INR/warfarin dose (WMD: -8.1, 95% CI: -12.54, -3.66). CYP2C9 and VKORC1 were observed with a shorter time to first therapeutic INR (WMD: -1.92, 95% CI: -3.23, -0.61) and stable INR/warfarin dose (WMD: -4.6, 95% CI: -6.87, -2.34) along with a longer TTR (%) (WMD: 3.91, 95% CI:1.18, 6.63). CYP2C9, VKORC1 and CYP4F2 were observed with a reduced proportion of patients with supra-therapeutic INR (OR: 0.68, 95% CI: 0.49, 0.93). Trial sequential analysis confirms the superior benefits of CYP2C9 with VKORC1 genotype. What is new and conclusion:The present evidence is supportive of personalizing warfarin dose based only on CYP2C9 and VKORC1 genotypes compared to traditional strategies. More RCTs are needed to delineate any benefit for adding CYP4F2 to provide sufficient power for pooled analysis. No convincing evidence exists supporting the role of CYP2C9 alone.

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Development of an electrochemical DNA-based biosensor for the detection of the cardiovascular pharmacogenetic-altering SNP CYP2C9*3

Morais

Magalhães

Domingues

et al. 2023

Talanta

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CYP2C9 and VKORC1 genotyping for the quality of long-standing warfarin treatment in Russian patients

Cited by 8 publications

References 45 publications

Opposite Response to Vitamin K Antagonists: A Report of Two Cases and Systematic Review of Literature

Opposite Response to Vitamin K Antagonists: A Report of Two Cases and Systematic Review of Literature

A network meta‐analysis ofCYP2C9,CYP2C9withVKORC1andCYP2C9withVKORC1andCYP4F2genotype‐based warfarin dosing strategies compared to traditional

Development of an electrochemical DNA-based biosensor for the detection of the cardiovascular pharmacogenetic-altering SNP CYP2C9*3

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