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A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.
N Engl J Med. 2013 Dec 12; 369(24):2304-12.NEJM

Abstract

BACKGROUND

Observational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy.

METHODS

We conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism. The primary outcome was the percentage of time in the target range for the international normalized ratio (INR; target range, 2.0 to 3.0) in the 12-week period after the initiation of therapy. Owing to low enrollment, the two trials were combined for analysis. The primary outcome was assessed in patients who remained in the trial for at least 10 weeks.

RESULTS

A total of 548 patients were enrolled (273 patients in the genotype-guided group and 275 in the control group). The follow-up was at least 10 weeks for 239 patients in the genotype-guided group and 245 in the control group. The percentage of time in the therapeutic INR range was 61.6% for patients receiving genotype-guided dosing and 60.2% for those receiving clinically guided dosing (P=0.52). There were no significant differences between the two groups for several secondary outcomes. The percentage of time in the therapeutic range during the first 4 weeks after the initiation of treatment in the two groups was 52.8% and 47.5% (P=0.02), respectively. There were no significant differences with respect to the incidence of bleeding or thromboembolic events.

CONCLUSIONS

Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy. (Funded by the European Commission Seventh Framework Programme and others; EU-PACT ClinicalTrials.gov numbers, NCT01119261 and NCT01119274.).

Authors+Show Affiliations

The authors' affiliations are listed in the Appendix.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24251360

Citation

Verhoef, Talitha I., et al. "A Randomized Trial of Genotype-guided Dosing of Acenocoumarol and Phenprocoumon." The New England Journal of Medicine, vol. 369, no. 24, 2013, pp. 2304-12.
Verhoef TI, Ragia G, de Boer A, et al. A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon. N Engl J Med. 2013;369(24):2304-12.
Verhoef, T. I., Ragia, G., de Boer, A., Barallon, R., Kolovou, G., Kolovou, V., Konstantinides, S., Le Cessie, S., Maltezos, E., van der Meer, F. J., Redekop, W. K., Remkes, M., Rosendaal, F. R., van Schie, R. M., Tavridou, A., Tziakas, D., Wadelius, M., Manolopoulos, V. G., & Maitland-van der Zee, A. H. (2013). A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon. The New England Journal of Medicine, 369(24), 2304-12. https://doi.org/10.1056/NEJMoa1311388
Verhoef TI, et al. A Randomized Trial of Genotype-guided Dosing of Acenocoumarol and Phenprocoumon. N Engl J Med. 2013 Dec 12;369(24):2304-12. PubMed PMID: 24251360.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon. AU - Verhoef,Talitha I, AU - Ragia,Georgia, AU - de Boer,Anthonius, AU - Barallon,Rita, AU - Kolovou,Genovefa, AU - Kolovou,Vana, AU - Konstantinides,Stavros, AU - Le Cessie,Saskia, AU - Maltezos,Efstratios, AU - van der Meer,Felix J M, AU - Redekop,William K, AU - Remkes,Mary, AU - Rosendaal,Frits R, AU - van Schie,Rianne M F, AU - Tavridou,Anna, AU - Tziakas,Dimitrios, AU - Wadelius,Mia, AU - Manolopoulos,Vangelis G, AU - Maitland-van der Zee,Anke H, AU - ,, Y1 - 2013/11/19/ PY - 2013/11/21/entrez PY - 2013/11/21/pubmed PY - 2013/12/20/medline SP - 2304 EP - 12 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 369 IS - 24 N2 - BACKGROUND: Observational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy. METHODS: We conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism. The primary outcome was the percentage of time in the target range for the international normalized ratio (INR; target range, 2.0 to 3.0) in the 12-week period after the initiation of therapy. Owing to low enrollment, the two trials were combined for analysis. The primary outcome was assessed in patients who remained in the trial for at least 10 weeks. RESULTS: A total of 548 patients were enrolled (273 patients in the genotype-guided group and 275 in the control group). The follow-up was at least 10 weeks for 239 patients in the genotype-guided group and 245 in the control group. The percentage of time in the therapeutic INR range was 61.6% for patients receiving genotype-guided dosing and 60.2% for those receiving clinically guided dosing (P=0.52). There were no significant differences between the two groups for several secondary outcomes. The percentage of time in the therapeutic range during the first 4 weeks after the initiation of treatment in the two groups was 52.8% and 47.5% (P=0.02), respectively. There were no significant differences with respect to the incidence of bleeding or thromboembolic events. CONCLUSIONS: Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy. (Funded by the European Commission Seventh Framework Programme and others; EU-PACT ClinicalTrials.gov numbers, NCT01119261 and NCT01119274.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/24251360/A_randomized_trial_of_genotype_guided_dosing_of_acenocoumarol_and_phenprocoumon_ L2 - http://www.nejm.org/doi/full/10.1056/NEJMoa1311388?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -