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Genotype-Guided Dosing of Coumarin Anticoagulants: A Meta-analysis of Randomized Controlled Trials.
J Cardiovasc Pharmacol Ther. 2015 Jul; 20(4):387-94.JC

Abstract

BACKGROUND

Coumarin anticoagulants (acenocoumarol, phenprocoumon, and warfarin) are generally used for the prevention of stroke in patients with atrial fibrillation or for the therapy and prevention of venous thromboembolism. However, the safe use of coumarin anticoagulants is restricted by a narrow therapeutic window and large interindividual dosing variations. Some studies found that the effectiveness and safety of coumarin anticoagulants therapy were increased by pharmacogenetic-guided dosing algorithms, while others found no significant effect of genotype-guided therapy.

METHODS

Four electronic databases were searched from January 1, 2000, to March 1, 2014, for randomized controlled trials of patients who received coumarin anticoagulants according to genotype-guided dosing algorithms. The primary outcome was the percentage of time that the international normalized ratio (INR) was within the normal range (2.0-3.0). Secondary outcomes included major bleeding events, thromboembolic events, and INR ≥4 events.

RESULTS

Eight studies satisfied the inclusion and exclusion criteria. Genotype-guided dosing of coumarin anticoagulants improved the percentage of time within the therapeutic INR range (95% confidence interval [CI], 0.02-0.28; P = .02; I(2) = 70%). Subgroup analysis was performed after dividing the nongenotype-guided group into a standard-dose group (95% CI, 0.14-0.49; P = .0004; I(2) = 50%) and a clinical variables-guided dosing algorithm group (95% CI, -0.07-0.15; P = .48; I(2) = 34%). There is a statistically significant reduction in numbers of secondary outcomes (INR ≥4 events, major bleeding events, and thromboembolic events; 95% CI, 0.79-1.00; P = .04). Subgroup analysis of secondary outcomes showed no significant difference between genotype-guided dosing and clinical variables-guided dosing (95% CI, 0.84-1.10; P = .57; I(2) = 11%), but genotype-guided dosing reduced secondary outcomes compared with standard dosing (95% CI, 0.62-0.92; P = .006; I(2) = 0%).

CONCLUSIONS

This meta-analysis showed that genotype-guided dosing increased the effectiveness and safety of coumarin therapy compared with standard dosing but did not have advantages compared with clinical variables-guided dosing.

Authors+Show Affiliations

Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.Department of Ophthalmology, Tai Zhou Hospital of Zhejiang Province, Taizhou, China.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China Institute of Intervention Vessel, Tongji University, Shanghai, China zxpsibs@163.com cjr.limaoquan@163.vip.com.Department of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China Institute of Intervention Vessel, Tongji University, Shanghai, China zxpsibs@163.com cjr.limaoquan@163.vip.com.

Pub Type(s)

Comparative Study
Journal Article
Meta-Analysis

Language

eng

PubMed ID

25575537

Citation

Tang, Tao, et al. "Genotype-Guided Dosing of Coumarin Anticoagulants: a Meta-analysis of Randomized Controlled Trials." Journal of Cardiovascular Pharmacology and Therapeutics, vol. 20, no. 4, 2015, pp. 387-94.
Tang T, Liu J, Zuo K, et al. Genotype-Guided Dosing of Coumarin Anticoagulants: A Meta-analysis of Randomized Controlled Trials. J Cardiovasc Pharmacol Ther. 2015;20(4):387-94.
Tang, T., Liu, J., Zuo, K., Cheng, J., Chen, L., Lu, C., Han, S., Xu, J., Jia, Z., Ye, M., Pei, E., Zhang, X., & Li, M. (2015). Genotype-Guided Dosing of Coumarin Anticoagulants: A Meta-analysis of Randomized Controlled Trials. Journal of Cardiovascular Pharmacology and Therapeutics, 20(4), 387-94. https://doi.org/10.1177/1074248414565666
Tang T, et al. Genotype-Guided Dosing of Coumarin Anticoagulants: a Meta-analysis of Randomized Controlled Trials. J Cardiovasc Pharmacol Ther. 2015;20(4):387-94. PubMed PMID: 25575537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotype-Guided Dosing of Coumarin Anticoagulants: A Meta-analysis of Randomized Controlled Trials. AU - Tang,Tao, AU - Liu,Jie, AU - Zuo,Keqiang, AU - Cheng,Jie, AU - Chen,Linyin, AU - Lu,Chenhui, AU - Han,Shilong, AU - Xu,Jichong, AU - Jia,Zhongzhi, AU - Ye,Meng, AU - Pei,Erli, AU - Zhang,Xiaoping, AU - Li,Maoquan, Y1 - 2015/01/08/ PY - 2014/08/20/received PY - 2014/11/14/accepted PY - 2015/1/11/entrez PY - 2015/1/13/pubmed PY - 2016/3/22/medline KW - anticoagulation KW - coumarin KW - genotype guided KW - meta-analysis SP - 387 EP - 94 JF - Journal of cardiovascular pharmacology and therapeutics JO - J. Cardiovasc. Pharmacol. Ther. VL - 20 IS - 4 N2 - BACKGROUND: Coumarin anticoagulants (acenocoumarol, phenprocoumon, and warfarin) are generally used for the prevention of stroke in patients with atrial fibrillation or for the therapy and prevention of venous thromboembolism. However, the safe use of coumarin anticoagulants is restricted by a narrow therapeutic window and large interindividual dosing variations. Some studies found that the effectiveness and safety of coumarin anticoagulants therapy were increased by pharmacogenetic-guided dosing algorithms, while others found no significant effect of genotype-guided therapy. METHODS: Four electronic databases were searched from January 1, 2000, to March 1, 2014, for randomized controlled trials of patients who received coumarin anticoagulants according to genotype-guided dosing algorithms. The primary outcome was the percentage of time that the international normalized ratio (INR) was within the normal range (2.0-3.0). Secondary outcomes included major bleeding events, thromboembolic events, and INR ≥4 events. RESULTS: Eight studies satisfied the inclusion and exclusion criteria. Genotype-guided dosing of coumarin anticoagulants improved the percentage of time within the therapeutic INR range (95% confidence interval [CI], 0.02-0.28; P = .02; I(2) = 70%). Subgroup analysis was performed after dividing the nongenotype-guided group into a standard-dose group (95% CI, 0.14-0.49; P = .0004; I(2) = 50%) and a clinical variables-guided dosing algorithm group (95% CI, -0.07-0.15; P = .48; I(2) = 34%). There is a statistically significant reduction in numbers of secondary outcomes (INR ≥4 events, major bleeding events, and thromboembolic events; 95% CI, 0.79-1.00; P = .04). Subgroup analysis of secondary outcomes showed no significant difference between genotype-guided dosing and clinical variables-guided dosing (95% CI, 0.84-1.10; P = .57; I(2) = 11%), but genotype-guided dosing reduced secondary outcomes compared with standard dosing (95% CI, 0.62-0.92; P = .006; I(2) = 0%). CONCLUSIONS: This meta-analysis showed that genotype-guided dosing increased the effectiveness and safety of coumarin therapy compared with standard dosing but did not have advantages compared with clinical variables-guided dosing. SN - 1940-4034 UR - https://www.unboundmedicine.com/medline/citation/25575537/Genotype_Guided_Dosing_of_Coumarin_Anticoagulants:_A_Meta_analysis_of_Randomized_Controlled_Trials_ L2 - http://journals.sagepub.com/doi/full/10.1177/1074248414565666?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -