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 - AUTHOR GROUP
AU - Daly, Ann
AU - Haschke-Becher, Elisabeth
AU - Kamali, Farhad
AU - Redekop, Ken
AU - Stingl, Julia
AU - Pirmohamed, Munir
AU - Grounidis, Georgios
AU - Kikas, Petros
AU - Mitrousi, Konstantina
AU - Kouroumichakis, Ioannis
AU - Maounis, Themistocles
AU - van der Wateren, Wilma
AU - Straasheijm-Veldhuis, Brianda
AU - Bayat, Samira
AU - Buikema, Myrre
AU - Zuurhout, Miranda
AU - Hegazy, Hoda
AU - Dorenbos, Brenda
AU - Beltman, Peter
AU - Hoeben, Edwin
AU - Vellenga, Arjan
AU - Karwar, Zamiera
AU - Hasrat, Fazila
AU - Hammoud, Siham
AU - Hagemans, Inge
AU - Berbee, Jaqueline
AU - van der Meer, Simone
AU - Verdoorn, Sanne
AU - Kraaijeveld, Judith
AU - Zwinderman, Koos
AU - Koster, Ruud
PY - 2013
Y1 - 2013
N2 - BackgroundObservational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy. MethodsWe 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. ResultsA 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. ConclusionsGenotype-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.)
AB - BackgroundObservational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy. MethodsWe 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. ResultsA 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. ConclusionsGenotype-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.)
U2 - https://doi.org/10.1056/NEJMoa1311388
DO - https://doi.org/10.1056/NEJMoa1311388
M3 - Article
C2 - 24251360
SN - 0028-4793
VL - 369
SP - 2304
EP - 2312
JO - New England journal of medicine
JF - New England journal of medicine
IS - 24
ER -