Boonyawat Kochawan, Wang Luqi, Lazo-Langner Alejandro, Kovacs Michael J, Yeo Erik, Schnurr Terri, Schulman Sam, Crowther Mark A
Kochawan Boonyawat, Department of Medicine, Ramathibodi Hospital, 270 Rama 6th Rd, Rachathewi, Bangkok, Thailand 10400, E-mail:
Thromb Haemost. 2016 Aug 30;116(3):480-5. doi: 10.1160/TH16-04-0320. Epub 2016 Jun 23.
The anticoagulant effect of warfarin is influenced by variations in vitamin K intake. Concomitant use of daily low-dose oral vitamin K (LDVK) and warfarin may improve INR stability. We hypothesise that administration of LDVK improves INR control. To test this hypothesis we performed a multi-centre, placebo-controlled, randomised trial conducted at four university-affiliated hospitals in Canada. Patients on chronic warfarin therapy received oral vitamin K 150 mcg daily or a matching placebo for a total of six months after a one-month run in period. The primary outcome was a comparison of mean time in therapeutic range (TTR) in LDVK and placebo group during a six-month-period. The secondary outcome was number of INR excursions <1.5 or >4.5. There was no significant difference in the final TTR between the two groups (65.1 % vs 66 %, p =0.8). Mean TTR in both LDVK and placebo groups were statistically increased compared with prior to the study. The number of INR excursions were significantly decreased in the LDVK group (9.4 % and 5.4 %, absolute difference [pre- minus post-] = 4 %, 95 % CI, 2 to 6 %, p-value <0.001). We conclude that LDVK administration did not increase mean TTR, but did decrease the number of INR excursions. The observed improvement in mean TTR in both groups suggests that more attentive monitoring of warfarin therapy, rather than LDVK, was responsible for the improvement in TTR observed. The reduced excursions suggest that LDVK did reduce extreme INR variation. The study is registered at www.ClinicalTrial.gov# NCT00990158.
华法林的抗凝作用受维生素K摄入量变化的影响。每日低剂量口服维生素K（LDVK）与华法林联合使用可能会改善国际标准化比值（INR）的稳定性。我们假设服用LDVK可改善INR的控制。为验证这一假设，我们在加拿大的四家大学附属医院进行了一项多中心、安慰剂对照的随机试验。接受慢性华法林治疗的患者在经过1个月的导入期后，每天口服150微克维生素K1或匹配的安慰剂，共持续6个月。主要结局是比较LDVK组和安慰剂组在6个月期间处于治疗范围内的平均时间（TTR）。次要结局是INR波动<1.5或>4.5的次数。两组最终的TTR无显著差异（65.1%对66%，p = 0.8）。与研究前相比，LDVK组和安慰剂组的平均TTR在统计学上均有所增加。LDVK组的INR波动次数显著减少（9.4%和5.4%，绝对差值[治疗前减去治疗后]=4%，95%置信区间，2%至6%，p值<）。我们得出结论，服用LDVK并未增加平均TTR，但确实减少了INR波动的次数。两组平均TTR的改善表明，对华法林治疗更密切的监测而非LDVK导致了观察到的TTR改善。波动次数减少表明LDVK确实减少了INR的极端变化。该研究已在www.ClinicalTrial.gov上注册，注册号为NCT00990158。
