The efficacy of low-dose warfarin initiation (3 mg versus 5 mg) in newly diagnosed venous thromboembolism patients among a population with a high prevalence of warfarin-sensitive haplotype of the VKORC1 gene: a randomized controlled trial

• Published in: Hematology (Luxembourg) Vol. 27; no. 1; pp. 95 - 104
• Main Authors: Suwanawiboon, Bundarika, Rotchanapanya, Wannaphorn, Mahaprom, Komkrit, Thongnoppakhun, Wanna, Lalerd, Yupaporn, Limwongse, Chanin, Sermsathanasawadi, Nuttawut, Owattanapanich, Weerapat
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 31-12-2022; Taylor & Francis Group
• Subjects: Adult; Anticoagulants - administration & dosage; Anticoagulants - therapeutic use; Dose-Response Relationship, Drug; Efficacy; Female; Humans; initiating dose; Male; Middle Aged; Prevalence; Treatment Outcome; venous thromboembolism; Venous Thromboembolism - drug therapy; Venous Thromboembolism - genetics; Vitamin K Epoxide Reductases - genetics; VKORC1; warfarin; Warfarin - administration & dosage; Warfarin - therapeutic use; VKORC1; Efficacy; venous thromboembolism; initiating dose; warfarin
• ISSN: 1607-8454; 1607-8454
• DOI: 10.1080/16078454.2021.2019891

The fact that a lower warfarin maintenance dose is required by Asian populations is well-known. Currently, the American College of Chest Physicians recommends commencing warfarin at a dose between 5 and 10 mg for venous thromboembolism (VTE). However, the optimal initiating dose in Asians is unknown. This study aimed to evaluate the efficacy of a 3 mg versus a 5 mg of warfarin initiating dose and a corresponding nomogram in patients with VTE.
Eligible patients were randomized to receive 3 mg or 5 mg per day warfarin for the first 2 days of treatment. The subsequent dose was adjusted according to the warfarin nomogram. The primary outcome was the number of patients who achieved an INR 2.0-3.0 within 8 days.
Fifty-six patients were enrolled. There was no significant difference in baseline characteristics between the groups. Seventeen (60.7%) patients in the 3-mg group and 22 (78.6%) patients in the 5-mg group achieved a therapeutic INR within 8 days (p = 0.146). However, there were significantly more patients in the 5-mg group who achieved the target INR on day 5 (53.6% vs 25.0%, p = 0.029). Furthermore, VKORC1-1639G > A was associated with an increased likelihood to achieve the target INR within 5 days (OR 3.81, 95%CI 1.19-12.16, p = 0.021).
The efficacy of a 3 mg warfarin starting dose with subsequent dose adjustment was similar to that of 5 mg on day 8 after warfarin initiation. However, a 5 mg initiating dose resulted in more patients who achieved therapeutic INR on day 5.