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Meta-Analysis of Genotype-Guided Versus Standard Dosing of Vitamin K Antagonists.

Publication ,  Journal Article
Kheiri, B; Abdalla, A; Haykal, T; Osman, M; Ahmed, S; Hassan, M; Bachuwa, G
Published in: The American journal of cardiology
April 2018

Vitamin K antagonist (VKA) is a commonly prescribed anticoagulant with a narrow therapeutic window. Genetic polymorphisms account for high VKA dosage variability. Hence, we performed an updated meta-analysis of all randomized clinical trials (RCTs) comparing genotype-guided VKA versus standard dosing algorithms. We conducted a systematic search of electronic databases from inception to October 2017 for all RCTs. The primary outcome was the percentage of time in therapeutic range (TTR). Secondary outcomes were international normalized ratio >4, major and all bleeding events, thromboembolism, adverse and serious adverse events, and all-cause mortality. We calculated the weighted mean difference for the primary outcome and risk ratio (RR) for secondary outcomes using a random-effect model. We included 20 RCTs and analyzed a total of 5,980 adult patients. Our pooled analysis showed greater improvement in TTR for the genotype-guided group in comparison with the standard group (mean difference 3.41%, 95% confidence interval [CI] 0.71 to 6.10, p = 0.01). In addition, there were significant reductions in major and all bleeding events ((RR 0.35, 95% CI 0.20 to 0.63, p = 0.0004) and (RR 0.79, 95% CI 0.66 to 0.95, p = 0.01), respectively). However, there were no significant differences between the groups for international normalized ratio >4 (RR 0.89, 95% CI 0.80 to 1.00, p = 0.06), thromboembolism (RR 0.81, 95% CI 0.56 to 1.17, p = 0.25), serious adverse events (RR 0.79, 95% CI 0.61 to 1.03, p = 0.08), any adverse events (RR 0.94, 95% CI 0.88 to 1.01, p = 0.07), or all-cause mortality (RR 0.73, 95% CI 0.32 to 1.66, p = 0.46). In conclusion, genotype-guided VKA dosing can improve the TTR and reduce the risk for bleeding episodes, in comparison with standard dosing algorithms.

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Published In

The American journal of cardiology

DOI

EISSN

1879-1913

ISSN

0002-9149

Publication Date

April 2018

Volume

121

Issue

7

Start / End Page

879 / 887

Related Subject Headings

  • Warfarin
  • Vitamin K
  • Thromboembolism
  • Phenprocoumon
  • Pharmacogenomic Variants
  • Pharmacogenomic Testing
  • Odds Ratio
  • Mortality
  • International Normalized Ratio
  • Humans
 

Citation

APA
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ICMJE
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Kheiri, B., Abdalla, A., Haykal, T., Osman, M., Ahmed, S., Hassan, M., & Bachuwa, G. (2018). Meta-Analysis of Genotype-Guided Versus Standard Dosing of Vitamin K Antagonists. The American Journal of Cardiology, 121(7), 879–887. https://doi.org/10.1016/j.amjcard.2017.12.023
Kheiri, Babikir, Ahmed Abdalla, Tarek Haykal, Mohammed Osman, Sahar Ahmed, Mustafa Hassan, and Ghassan Bachuwa. “Meta-Analysis of Genotype-Guided Versus Standard Dosing of Vitamin K Antagonists.The American Journal of Cardiology 121, no. 7 (April 2018): 879–87. https://doi.org/10.1016/j.amjcard.2017.12.023.
Kheiri B, Abdalla A, Haykal T, Osman M, Ahmed S, Hassan M, et al. Meta-Analysis of Genotype-Guided Versus Standard Dosing of Vitamin K Antagonists. The American journal of cardiology. 2018 Apr;121(7):879–87.
Kheiri, Babikir, et al. “Meta-Analysis of Genotype-Guided Versus Standard Dosing of Vitamin K Antagonists.The American Journal of Cardiology, vol. 121, no. 7, Apr. 2018, pp. 879–87. Epmc, doi:10.1016/j.amjcard.2017.12.023.
Kheiri B, Abdalla A, Haykal T, Osman M, Ahmed S, Hassan M, Bachuwa G. Meta-Analysis of Genotype-Guided Versus Standard Dosing of Vitamin K Antagonists. The American journal of cardiology. 2018 Apr;121(7):879–887.
Journal cover image

Published In

The American journal of cardiology

DOI

EISSN

1879-1913

ISSN

0002-9149

Publication Date

April 2018

Volume

121

Issue

7

Start / End Page

879 / 887

Related Subject Headings

  • Warfarin
  • Vitamin K
  • Thromboembolism
  • Phenprocoumon
  • Pharmacogenomic Variants
  • Pharmacogenomic Testing
  • Odds Ratio
  • Mortality
  • International Normalized Ratio
  • Humans