Yasaka M, Yamaguchi T
Cerebrovascular Division, Department of Medicine, National Cardiovascular Center, Osaka, Japan.
CNS Drugs. 2001;15(8):623-31. doi: 10.2165/00023210-200115080-00005.
Nonvalvular atrial fibrillation (NVAF) is frequently seen in elderly people and has become a main cause of cardioembolic stroke. The efficacy of anticoagulation for primary prevention of stroke or transient ischaemic attacks (TIAs) in patients with NVAF has been established by prospective, randomised and controlled trials. Warfarin decreased the frequency of all strokes by 68% and the rate of the combined outcome of stroke, systemic embolism or death by 48%. Anticoagulation with warfarin using international normalised ratios (INRs) ranging from 2.0 to 3.0 is recommended for patients with NVAF, who have any of the risk factors identified by the Atrial Fibrillation Investigators (AFI) [previous stroke or TIA, history of hypertension, diabetes mellitus, advanced age (> or = 65 years old), congestive heart failure and coronary artery disease], the American College of Chest Physicians (ACCP) [increased age (> 75 years old), prior stroke, hypertension and heart failure], or the Stroke Prevention in Atrial Fibrillation (SPAF) investigators [women > 75 years old, prior stroke, systolic blood pressure > 160mm Hg, recent heart failure, and fractional shortening < 25% on echocardiography]. For the secondary prevention of stroke, the efficacy of adjusted-dose warfarin therapy has been demonstrated by 2 major randomised trials. SPAF III (INR 2.0 to 3.0) demonstrated a lower incidence of ischaemic stroke or systemic embolism (3.4 %/year) compared with low fixed-dose warfarin plus aspirin (acetylsalicylic acid) [11.9%]. The European Atrial Fibrillation Trial [EAFT] (INR 2.5 to 4.0) showed a lower incidence of all stroke (4.0 %/year) with adjusted-dose warfarin compared with placebo (12.0 %/year). The incidence of major bleeding in the adjusted-dose warfarin group in SPAF III and EAFT was 2.4 and 2.8 %/year, respectively. EAFT incidence rates for the occurrence of a first ischaemic or haemorrhagic complication analysed by INR range indicated that the rate was lowest at INRs of 2.0 to 2.9, and higher with INRs of 3.0 to 3.9. Therefore, the optimal intensity of anticoagulation for prevention of recurrent stroke seems to be an INR of between 2.0 and 3.0, as for primary prevention. Retrospective and prospective studies from Japan reported that in the elderly, haemorrhagic complications occur frequently with INRs above 2.6 and major ischaemic events cannot be prevented at INRs below 1.6. Therefore, an INR target between 1.6 and 2.6 may be an alternative for secondary prevention of stroke in elderly patients with NVAF who have a potential risk of bleeding, to avoid both major ischaemic and haemorrhagic events. Antiplatelets may be administered in patients who are unable to manage taking warfarin properly or who have a high risk of falling and subsequently sustaining a head injury, although the efficacy of antiplatelets for secondary prevention of stroke in NVAF has not yet been established.
非瓣膜性心房颤动（NVAF）在老年人中较为常见，已成为心源性栓塞性卒中的主要原因。前瞻性、随机对照试验已证实抗凝治疗对NVAF患者预防卒中或短暂性脑缺血发作（TIA）的疗效。华法林使所有卒中的发生率降低了68%，使卒中、全身性栓塞或死亡的联合结局发生率降低了48%。对于有房颤研究人员（AFI）确定的任何危险因素[既往卒中或TIA、高血压病史、糖尿病、高龄（≥65岁）、充血性心力衰竭和冠状动脉疾病]、美国胸科医师学会（ACCP）[年龄增加（>75岁）、既往卒中、高血压和心力衰竭]或心房颤动卒中预防（SPAF）研究人员确定的危险因素[75岁以上女性、既往卒中、收缩压>160mmHg、近期心力衰竭以及超声心动图显示缩短分数<25%]的NVAF患者，建议使用国际标准化比值（INR）在2.0至3.0范围内的华法林进行抗凝治疗。对于卒中的二级预防，两项主要的随机试验已证明调整剂量的华法林治疗的疗效。SPAF III（INR 2.0至3.0）显示，与低固定剂量华法林加阿司匹林（乙酰水杨酸）相比，缺血性卒中或全身性栓塞的发生率较低（3.4%/年）[11.9%]。欧洲心房颤动试验[EAFT]（INR 2.5至4.0）显示，与安慰剂（12.0%/年）相比，调整剂量的华法林治疗使所有卒中的发生率较低（4.0%/年）。SPAF III和EAFT中调整剂量华法林组的大出血发生率分别为2.4%/年和2.8%/年。EAFT按INR范围分析的首次缺血性或出血性并发症发生率表明，在INR为2.0至2.9时发生率最低，在INR为3.0至3.9时发生率较高。因此，预防复发性卒中的最佳抗凝强度似乎与一级预防一样，为INR在2.0至3.0之间。日本的回顾性和前瞻性研究报告称，在老年人中，INR高于2.6时出血并发症频繁发生，而INR低于1.6时无法预防重大缺血事件。因此，对于有出血潜在风险的老年NVAF患者，INR目标在1.6至2.6之间可能是卒中二级预防的替代方案，以避免重大缺血和出血事件。对于无法正确服用华法林或有跌倒及随后头部受伤高风险的患者，可给予抗血小板药物治疗，尽管抗血小板药物对NVAF患者卒中二级预防的疗效尚未确定。
