心房颤动抗拴治疗实践_马长生.pptVIP

日本华法林使用计量的研究 低剂量华法林（INR维持于1.6～2.6）抗凝治疗，严重出血和颅内出血发生率分别为每人年2.38%和每人年0.60%，显著高于西方人，INR≥2.27是严重出血的独立危险因素之一。 房颤导管消融恢复窦律改善预后 * 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 pharmacogenetic and clinical factors improved the accuracy and efficiency of warfarin dose initiation. Despite this, the primary end point of a reduction in out-of-range INRs was not achieved. In subset analyses, pharmacogenetic guidance showed promise for wild-type and multiple variant genotypes. (Circulation. 2007;116:2563-2570.) ACTIVE-W 试验为非劣性比较，随机对比房颤患者氯吡格雷7