Diener Hans-Christoph, Bogousslavsky Julien, Brass Lawrence M, Cimminiello Claudio, Csiba Laszlo, Kaste Markku, Leys Didier, Matias-Guiu Jordi, Rupprecht Hans-Jürgen
Department of Neurology, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Lancet. 2004;364(9431):331-7. doi: 10.1016/S0140-6736(04)16721-4.
Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease in the CAPRIE study and its benefit was amplified in some high-risk subgroups of patients. We aimed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk.
We did a randomised, double-blind, placebo-controlled trial to compare aspirin (75 mg/day) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day. Duration of treatment and follow-up was 18 months. The primary endpoint was a composite of ischaemic stroke, myocardial infarction, vascular death, or rehospitalisation for acute ischaemia (including rehospitalisation for transient ischaemic attack, angina pectoris, or worsening of peripheral arterial disease). Analysis was by intention to treat, using logrank test and a Cox's proportional-hazards model.
596 (15.7%) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 (16.7%) in the clopidogrel alone group (relative risk reduction 6.4%, [95% CI -4.6 to 16.3]; absolute risk reduction 1% [-0.6 to 2.7]). Life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone (96 [2.6%] vs 49 [1.3%]; absolute risk increase 1.3% [95% CI 0.6 to 1.9]). Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality.
Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events. However, the risk of life-threatening or major bleeding is increased by the addition of aspirin.
在CAPRIE研究中，氯吡格雷在有动脉粥样硬化血栓形成疾病既往表现的患者中优于阿司匹林，其益处在一些高危患者亚组中得到放大。我们旨在评估在氯吡格雷基础上加用阿司匹林在预防血管事件方面是否比单用氯吡格雷有更大益处，同时潜在出血风险可能更高。
我们进行了一项随机、双盲、安慰剂对照试验，在7599例近期发生缺血性卒中或短暂性脑缺血发作且至少有一项额外血管危险因素、已接受每日75毫克氯吡格雷治疗的高危患者中，比较阿司匹林（每日75毫克）与安慰剂。治疗和随访持续时间为18个月。主要终点是缺血性卒中、心肌梗死、血管性死亡或因急性缺血再次住院（包括因短暂性脑缺血发作、心绞痛或外周动脉疾病恶化再次住院）的复合终点。采用意向性分析，使用对数秩检验和Cox比例风险模型。
接受阿司匹林和氯吡格雷治疗的组中有596例（15.7%）患者达到主要终点，而单用氯吡格雷组中有636例（16.7%）（相对风险降低6.4%，[95%可信区间 -4.6至16.3]；绝对风险降低1%[-0.6至2.7]）。接受阿司匹林和氯吡格雷治疗的组中危及生命的出血高于单用氯吡格雷组（96例[2.6%]对49例[1.3%]；绝对风险增加1.3%[95%可信区间0.6至1.9]）。接受阿司匹林和氯吡格雷治疗的组中主要出血也有所增加，但死亡率无差异。
在近期发生缺血性卒中或短暂性脑缺血发作的高危患者中，在氯吡格雷基础上加用阿司匹林在减少主要血管事件方面无显著差异。然而，加用阿司匹林会增加危及生命或主要出血的风险。
