华法林在房颤治疗中的应用及INR的监测_马长生.pptVIP

华法林在房颤治疗中的应用及INR的监测 近期心衰史 CHF 高血压病史 HP ≥ 75岁 AGE 糖尿病 DM 脑卒中TIA Stroke  华法林初始剂量5-10mg,随后根据INR调整 首次服用华法林后2-3天查INR INR值稳定的患者，至少4周查一次 男性79岁，体检时发现房颤 第一位医生建议他应用华法林抗凝治疗，3mg QN，并告之3天后查INR 该患者遵医嘱服药，3天后INR为2.3 患者请另外一个医生帮他看了化验单，医生看到INR在治疗范围后，告之继续按原来的方案服药，每月复查一次INR 半个月后，患者出现昏迷， 磁共振检查证实为颅内出血，当时INR为13.8，昏迷10天后，患者死亡 67岁男性患者，AF术后服用华法林治疗 服用2mg/d的第5天及第10天INR均为2.3 1个月后患者出现左下腹疼痛，超声示腹膜后血(10×10×14cm)。INR5.65 患者1个月内无服用药物的增减,无特殊饮食改变 尽量多地提高检测频率 每周检测能保证85%的INR处于靶目标范围内 每月检测仅50%的的INR处于靶目标范围内  两组监测INR的频率相同 Background—Pharmacogenetic-guided dosing of warfarin is a promising application of “personalized medicine” but has not been adequately tested in randomized trials. Methods and Results—Consenting patients (n206) being initiated on warfarin were randomized to pharmacogeneticguided or standard dosing. Buccal swab DNA was genotyped for CYP2C9 *2 and CYP2C9 *3 and VKORC1 C1173T with a rapid assay. Standard dosing followed an empirical protocol, whereas pharmacogenetic-guided dosing followed a regression equation including the 3 genetic variants and age, sex, and weight. Prothrombin time international normalized ratio (INR) was measured routinely on days 0, 3, 5, 8, 21, 60, and 90. A research pharmacist unblinded to treatment strategy managed dose adjustments. Patients were followed up for up to 3 months. Pharmacogenetic-guided predicted doses more accurately approximated stable doses (P0.001), resulting in smaller (P0.002) and fewer (P0.03) dosing changes and INRs (P0.06). However, percent out-of-range INRs (pharmacogenetic30.7%, standard33.1%), the primary end point, did not differ significantly between arms. Despite this, when restricted to wild-type patients (who required larger doses; P0.001) and multiple variant carriers (who required smaller doses; P0.001) in exploratory analyses, results (pharmacogenetic29%, standard39%) achieved nominal significance (P0.03). Multiple variant allele carriers were at increased risk of an INR of 4 (P0.03). Conclusions—An algorithm guided by pharma