van Rein Nienke, Biedermann J S, Bonafacio S M, Kruip M J H A, van der Meer F J M, Lijfering W M
Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Eur J Clin Pharmacol. 2016 Dec;72(12):1441-1447. doi: 10.1007/s00228-016-2138-6. Epub 2016 Oct 5.
The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs).
We selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test.
Four hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower.
Initiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.
本研究旨在确定他汀类药物对接受维生素K拮抗剂(VKA)治疗患者凝血功能的即刻和长期影响。
我们选取了荷兰两家抗凝门诊正在接受VKA治疗且于2009年至2013年间开始使用他汀类药物的患者。排除在随访期间开始或停用与VKA相互作用的伴随药物或住院的患者。将开始使用他汀类药物后的VKA剂量(毫克/天)与开始使用他汀类药物前的最后一次VKA剂量进行比较。使用配对学生t检验计算VKA剂量在即刻和长期(6周和12周时)的差异。
纳入了435名使用苯丙香豆素的患者(平均年龄70岁,60%为男性)和303名使用醋硝香豆素的患者(平均年龄69岁,58%为男性)。开始使用他汀类药物后,苯丙香豆素的即刻剂量降低了0.02毫克/天(95%置信区间,0.00至0.03)。在6周和12周时,与首次使用他汀类药物前的剂量相比,这些苯丙香豆素剂量分别降低了0.03(95%置信区间,0.01至0.05)和0.07毫克/天(95%置信区间,0.04至0.09)。在使用醋硝香豆素的患者中,VKA剂量降低了0.04毫克/天(95%置信区间,0.01至0.07)(即刻效应),0.10(95%置信区间,0.03至0.16)(6周时),以及0.11毫克/天(95%置信区间,0.04至0.18)(12周后)。
开始他汀类药物治疗与使用苯丙香豆素和醋硝香豆素的患者VKA剂量即刻和长期虽微小但具有统计学意义的降低相关,这表明他汀类药物可能具有抗凝特性。