Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan.
J Cardiol. 2009 Jun;53(3):355-60. doi: 10.1016/j.jjcc.2008.12.003. Epub 2009 Feb 8.
Oral anticoagulant therapy with warfarin is essential for the optimal prophylaxis of thrombosis and embolism in many vascular disorders whose prevalence is high among elderly patients. Elderly Caucasians show increased sensitivity to oral anticoagulants. Although the Japanese are more sensitive to warfarin therapy than Caucasians, the relationship between age and warfarin dosage in the Japanese has not been investigated in detail. Here, we investigated this relationship in Japanese patients.
The subjects comprised 102 outpatients (28-87 years) who showed a stable anticoagulant effect (prothrombin time expressed in terms of the international normalized ratio [PT-INR] between 1.6 and 2.6) following long-term warfarin therapy at the Department of Cardiovascular Medicine, National Hospital Organization Hakodate Hospital. The relationship between age, PT-INR, and daily warfarin dose was retrospectively investigated.
The mean values of the characteristics of all the patients were as follows: age, 70.7 (+/-10.5) years; daily dose of warfarin, 2.68 (+/-0.95)mg; PT-INR, 1.99 (+/-0.24). The PT-INR was not correlated with increasing age. The daily dosage of warfarin and the dosage adjusted according to the PT-INR (dose/PT-INR), wherein the lower values indicate a higher sensitivity to warfarin therapy, were significantly inversely correlated with age. In the high PT-INR (PT-INR>2.1) group, no significant difference was observed between the older and younger patients with regard to any characteristics. Conversely, in the low PT-INR (1.6 ≤ PT-INR ≤ 2.1) group, the dose/PT-INR was significantly reduced in the older patients (≥ 65 years); however, no significant difference was observed in the PT-INR value.
Both age and the controlled PT-INR value are factors responsible for the increasing sensitivity to warfarin in Japanese patients under optimal anticoagulant therapy. Since elderly Japanese patients with low PT-INR values are especially sensitive to warfarin, greater caution should be exercised while determining the dosage schedule in such patients.
华法林的口服抗凝治疗对于许多血管疾病的血栓和栓塞的最佳预防至关重要，而这些疾病在老年患者中的患病率很高。白种老年人对华法林的敏感性增加。虽然日本人对华法林治疗的敏感性比白种人高，但日本人的年龄与华法林剂量之间的关系尚未详细研究。在这里，我们研究了日本患者的这种关系。
本研究的对象是在北海道立函馆医院心血管医学系接受长期华法林治疗后，凝血酶原时间国际标准化比值（PT-INR）在 1.6 至 2.6 之间表现出稳定抗凝效果的 102 名门诊患者（28-87 岁）。回顾性研究年龄、PT-INR 和华法林日剂量之间的关系。
所有患者的特征平均值如下：年龄 70.7(+/-10.5)岁；华法林日剂量 2.68(+/-0.95)mg；PT-INR 1.99(+/-0.24)。PT-INR 与年龄的增加无关。华法林的日剂量和根据 PT-INR 调整的剂量（剂量/PT-INR），其中低值表示对华法林治疗的敏感性更高，与年龄呈显著负相关。在高 PT-INR（PT-INR>2.1）组中，年龄较大和较小的患者在任何特征方面均无显著差异。相反，在低 PT-INR（1.6≤PT-INR≤2.1）组中，年龄较大的患者（≥65 岁）的剂量/PT-INR 显著降低；然而，PT-INR 值没有差异。
年龄和控制的 PT-INR 值都是日本患者在最佳抗凝治疗下对华法林敏感性增加的因素。由于低 PT-INR 值的老年日本患者对华法林特别敏感，因此在确定此类患者的剂量方案时应更加谨慎。
