Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: The prevention regimen for effectively avoiding second strokes trial (PRoFESS)
Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: The prevention regimen for effectively avoiding second strokes trial (PRoFESS)
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DOI：
10.1159/000100105
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发表时间：
2007-01-01
影响因子：
2.9
通讯作者：
Yusuf, Salim
中科院分区：
文献类型：
--
作者：
Diener, Hans-Christoph;Sacco, Ralph;Yusuf, Salim
背景：患有短暂性脑缺血发作和缺血性卒中的个体具有卒中复发和死亡的高风险。虽然乙酰水杨酸（阿萨，阿司匹林）已被证明并被接受为这些患者的标准治疗，但最近的试验表明，阿萨和双嘧达莫（DP）或氯吡格雷的联合治疗可能上级阿萨。用血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂阻断肾素-血管紧张素系统也可减少卒中复发。正在进行的PRoFESS（有效避免二次卒中的预防方案）试验旨在评价阿萨+缓释DP与氯吡格雷相比是否有效，以及在卒中后个体常规治疗的基础上使用替米沙坦是否能降低进一步卒中的风险。方法：PRoFESS是一项多中心、随机、双盲试验，涉及35个国家或地区的695个中心。年龄>= 50岁、缺血性卒中< 120天且病情稳定的患者随机分组。该试验的主要结局是复发性卒中，采用时间-事件分析。最重要的次要结局是卒中、心肌梗死或血管性死亡的复合终点。其他次要结局包括该复合终点+充血性心力衰竭、新发糖尿病、其他指定的闭塞性血管事件（肺栓塞、深静脉血栓形成、外周动脉闭塞、短暂性脑缺血发作、脑静脉血栓形成或未归类为卒中的视网膜血管意外）、任何死亡、根据吐司标准和简易精神状态检查评分的卒中亚型。通过评估重大出血事件的风险来评价安全性。阿萨+ DP和氯吡格雷之间的比较是基于非劣效性的初步评估，然后是优效性的评估，而对于替米沙坦，我们将评估其相对于安慰剂的优效性。结果如下：超过20，000例患者随机化，并采用2 × 2析因设计，PRoFESS是研究预防复发性卒中的最大卒中试验。平均年龄为66.1 ± 88.6岁，36.0%的患者为女性。从合格事件到随机化的中位时间为15天，39.9%的患者在10天内随机化。根据吐司标准，28.5%的卒中是由于大血管疾病，52.1%是由于小血管疾病，1.8%是由于心源性栓塞，2.0%是由于其他确定的病因，15.5%是病因不明。结论：PRoFESS是迄今为止规模最大的卒中二级预防试验，将直接比较两种抗血小板治疗方案以及替米沙坦与安慰剂的获益。版权所有（c）2007 S. Karger AG，巴塞尔。
Background: Individuals with transient ischemic attack and ischemic stroke have a high risk of recurrent stroke and death. While acetylsalicylic acid (ASA, aspirin) is proven and accepted as standard therapy in these patients, recent trials demonstrate that a combination of ASA and dipyridamole (DP) or clopidogrel may be superior to ASA. Blocking the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may also reduce recurrent stroke. The ongoing PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial is designed to evaluate whether ASA + extended-release DP compared to clopidogrel, and whether telmisartan in addition to usual care in individuals after a stroke, will reduce the risk of further strokes. Methods: PRoFESS is a multicenter, randomized, double-blind trial involving 695 sites from 35 countries or regions. Patients >= 50 years presenting with an ischemic stroke < 120 days who were stable were randomized. The primary outcome for the trial is recurrent stroke, using a time-to-event analysis. The most important secondary outcome is the composite of stroke, myocardial infarction or vascular death. Other secondary outcomes include this composite + congestive heart failure, new-onset diabetes, other designated occlusive vascular events (pulmonary embolism, deep-vein thrombosis, peripheral arterial occlusion, transient ischemic attack, cerebral venous thrombosis or retinal vascular accident not classified as stroke), any death, stroke subtype by TOAST criteria and Mini Mental State Examination score. Safety is evaluated by assessing the risk of major hemorrhagic events. The comparison between ASA + DP and clopidogrel is based on an initial assessment of noninferiority, followed by evaluation of superiority, while for telmisartan, we will assess its superiority over placebo. Results: With over 20,000 patients randomized, and utilizing a 2 x 2 factorial design, PRoFESS is the largest stroke trial to investigate the prevention of recurrent stroke. The mean age was 66.1 +/- 8 8.6 years, and 36.0% of the patients were females. The median time from qualifying event to randomization was 15 days with 39.9% of patients randomized within 10 days. According to the TOAST criteria, 28.5% of the strokes were due to large-vessel disease, 52.1% to small-vessel disease, 1.8% to cardioembolism, and 2.0% to other determined etiologies and 15.5% were of undetermined etiology. Conclusions: PRoFESS is the largest secondary stroke prevention trial to date and will directly compare two antiplatelet regimens as well as the benefit of telmisartan versus placebo. Copyright (c) 2007 S. Karger AG, Basel.