Crowther Mark A, Ageno Walter, Garcia David, Wang Luqi, Witt Dan M, Clark Nathan P, Blostein Mark D, Kahn Susan R, Vesely Sara K, Schulman Sam, Kovacs Michael J, Rodger Marc A, Wells Phillip, Anderson David, Ginsberg Jeffery, Selby Rita, Siragusa Sergio, Silingardi Mauro, Dowd Mary Beth, Kearon Clive
McMaster University, Hamilton, Ontario, Canada.
Ann Intern Med. 2009 Mar 3;150(5):293-300. doi: 10.7326/0003-4819-150-5-200903030-00005.
Low-dose oral vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy. Its effects on bleeding events are uncertain.
To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy.
Multicenter, randomized, placebo-controlled trial. Randomization was computer-generated, and participants were allocated to trial groups by using sequentially numbered study drug containers. Patients, caregivers, and those who assessed outcomes were blinded to treatment assignment.
14 anticoagulant therapy clinics in Canada, the United States, and Italy.
Nonbleeding patients with INR values of 4.5 to 10.0.
Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed).
Bleeding events (primary outcome), thromboembolism, and death (secondary outcomes).
56 patients (15.8%) in the vitamin K group and 60 patients (16.3%) in the placebo group had at least 1 bleeding complication (absolute difference, -0.5 percentage point [95% CI, -6.1 to 5.1 percentage points]); major bleeding events occurred in 9 patients (2.5%) in the vitamin K group and 4 patients (1.1%) in the placebo group (absolute difference, 1.5 percentage points [CI, -0.8 to 3.7 percentage points]). Thromboembolism occurred in 4 patients (1.1%) in the vitamin K group and 3 patients (0.8%) in the placebo group (absolute difference, 0.3 percentage point [CI, -1.4 to 2.0 percentage points]). Other adverse effects were not assessed. The day after treatment, the INR had decreased by a mean of 1.4 in the placebo group and 2.8 in the vitamin K group (P < 0.001).
Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed.
Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0.
Canadian Institutes of Health Research and Italian Ministry of Universities and Research.
低剂量口服维生素K可降低接受华法林治疗的抗凝过度患者的国际标准化比值（INR）。其对出血事件的影响尚不确定。
观察低剂量口服维生素K是否能减少华法林相关性凝血病患者90天内的出血事件。
多中心、随机、安慰剂对照试验。随机分组由计算机生成，通过使用连续编号的研究药物容器将参与者分配到试验组。患者、护理人员和评估结果的人员对治疗分配情况不知情。
加拿大、美国和意大利的14家抗凝治疗诊所。
INR值为4.5至10.0的无出血患者。
口服1.25毫克维生素K（355例患者随机分组；347例纳入分析），或匹配的安慰剂（369例患者随机分组；365例纳入分析）。
出血事件（主要结局）、血栓栓塞和死亡（次要结局）。
维生素K组56例患者（15.8%）和安慰剂组60例患者（16.3%）至少发生1次出血并发症（绝对差异为-0.5个百分点[95%CI，-6.1至5.1个百分点]）；维生素K组9例患者（2.5%）发生大出血事件，安慰剂组4例患者（1.1%）发生大出血事件（绝对差异为1.5个百分点[CI，-0.8至3.7个百分点]）。维生素K组4例患者（1.1%）发生血栓栓塞，安慰剂组3例患者（0.8%）发生血栓栓塞（绝对差异为0.3个百分点[CI，-1.4至2.0个百分点]）。未评估其他不良反应。治疗后次日，安慰剂组INR平均下降1.4，维生素K组平均下降2.8（P<0.001）。
未纳入正在出血的患者，入组后未强制规定或跟踪华法林的剂量。
低剂量口服维生素K不能减少INR值为4.5至10.0的华法林使用者的出血情况。
加拿大卫生研究院和意大利大学与研究部。
