A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon
Talitha I Verhoef, Georgia Ragia, Anthonius de Boer, Rita Barallon, Genovefa Kolovou, Vana Kolovou, Stavros Konstantinides, Saskia Le Cessie, Efstratios Maltezos, Felix J M van der Meer, William K Redekop, Mary Remkes, Frits R Rosendaal, Rianne M F van Schie, Anna Tavridou, Dimitrios Tziakas, Mia Wadelius, Vangelis G Manolopoulos, Anke H Maitland-van der Zee, EU-PACT Group, Rita Barallon, Anthonius de Boer, Ann Daly, Elisabeth Haschke-Becher, Farhad Kamali, Anke-Hilse Maitland-van der Zee, Ken Redekop, Julia Stingl, Vangelis G Manolopoulos, Munir Pirmohamed, Frits R Rosendaal, Mia Wadelius, Georgios Grounidis, Petros Kikas, Konstantina Mitrousi, Ioannis Kouroumichakis, Themistocles Maounis, Wilma van der Wateren, Brianda Straasheijm-Veldhuis, Samira Bayat, Myrre Buikema, Miranda Zuurhout, Hoda Hegazy, Brenda Dorenbos, Peter Beltman, Edwin Hoeben, Arjan Vellenga, Zamiera Karwar, Fazila Hasrat, Siham Hammoud, Inge Hagemans, Jaqueline Berbee, Simone van der Meer, Sanne Verdoorn, Judith Kraaijeveld, Alexandra Babajeff, Saskia Boejharet, Annette Emerenciana, Nadia el Khedr, Amin Aoussar, Lukas van Hoorn, Ali Aziz, Milaad Elia, Tom Schalekamp, Aref Nasser, Marja Sukel, Desiree Verbeek-Janssen, Helga Vermaas, Milia Siauw, Judith Wessels, Koos Zwinderman, Elisabeth Palmcrantz-Graf, Niclas Eriksson, David Fitzmaurice, David Gurwitz, Kit Roes, Mirjam Bruggink, Béate ten Bokum, Nicky Michorius, Jos Hennen, Wolf Ondracek, Ingolf Cascorbi, Rene Eijkemans, Ruud Koster, Talitha I Verhoef, Georgia Ragia, Anthonius de Boer, Rita Barallon, Genovefa Kolovou, Vana Kolovou, Stavros Konstantinides, Saskia Le Cessie, Efstratios Maltezos, Felix J M van der Meer, William K Redekop, Mary Remkes, Frits R Rosendaal, Rianne M F van Schie, Anna Tavridou, Dimitrios Tziakas, Mia Wadelius, Vangelis G Manolopoulos, Anke H Maitland-van der Zee, EU-PACT Group, Rita Barallon, Anthonius de Boer, Ann Daly, Elisabeth Haschke-Becher, Farhad Kamali, Anke-Hilse Maitland-van der Zee, Ken Redekop, Julia Stingl, Vangelis G Manolopoulos, Munir Pirmohamed, Frits R Rosendaal, Mia Wadelius, Georgios Grounidis, Petros Kikas, Konstantina Mitrousi, Ioannis Kouroumichakis, Themistocles Maounis, Wilma van der Wateren, Brianda Straasheijm-Veldhuis, Samira Bayat, Myrre Buikema, Miranda Zuurhout, Hoda Hegazy, Brenda Dorenbos, Peter Beltman, Edwin Hoeben, Arjan Vellenga, Zamiera Karwar, Fazila Hasrat, Siham Hammoud, Inge Hagemans, Jaqueline Berbee, Simone van der Meer, Sanne Verdoorn, Judith Kraaijeveld, Alexandra Babajeff, Saskia Boejharet, Annette Emerenciana, Nadia el Khedr, Amin Aoussar, Lukas van Hoorn, Ali Aziz, Milaad Elia, Tom Schalekamp, Aref Nasser, Marja Sukel, Desiree Verbeek-Janssen, Helga Vermaas, Milia Siauw, Judith Wessels, Koos Zwinderman, Elisabeth Palmcrantz-Graf, Niclas Eriksson, David Fitzmaurice, David Gurwitz, Kit Roes, Mirjam Bruggink, Béate ten Bokum, Nicky Michorius, Jos Hennen, Wolf Ondracek, Ingolf Cascorbi, Rene Eijkemans, Ruud Koster
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.).
Source: PubMed