Amaro Sergio, Laredo Carlos, Renú Arturo, Llull Laura, Rudilosso Salvatore, Obach Víctor, Urra Xabier, Planas Anna M, Chamorro Ángel
From the Hospital Clinic of Barcelona (S.A., C.L., A.R., L.L., S.R., V.O., X.U., Á.C.); Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS) (S.A., C.L., A.R., L.L., S.R., V.O., X.U., Á.C.), and Institute for Biomedical Research of Barcelona (IIBB) (A.M.P.), Barcelona, Spain; and University of Barcelona, Spain (Á.C.).
Stroke. 2016 Nov;47(11):2874-2876. doi: 10.1161/STROKEAHA.116.014672. Epub 2016 Oct 6.
Identification of neuroprotective therapies in acute ischemic stroke is imperative. We report a predefined analysis of the URICO-ICTUS trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke) assessing the efficacy of uric acid (UA) compared with placebo to prevent early ischemic worsening (EIW) and the relevance of collateral circulation.
URICO-ICTUS was a double-blind, placebo-controlled, phase 2b trial where a total of 411 patients treated with alteplase within 4.5 hours of stroke onset were randomized (1:1) to receive UA 1000 mg (n=211) or placebo (n=200) before the end of alteplase infusion. EIW defined an increment ≥4 points in the National Institutes of Health Stroke Scale score within 72 hours of treatment in the absence of hemorrhage or recurrent stroke. Logistic regression models assessed the interaction between therapy and the collateral circulation in 112 patients who had a pretreatment computed tomographic angiography.
EIW occurred in 2 of 149 (1%) patients with good outcome and 23 of 262 (9%) patients with poor outcome (χ; P=0.002). EIW occurred in 7 of 204 (3%) patients treated with UA and in 18 of 200 (9%) patients treated with placebo (χ; P=0.01). There was a significant interaction between the efficacy of UA to prevent EIW and collaterals (P=0.029), with lower incidence in patients with good collaterals treated with UA compared with placebo (2% versus 15%, respectively; P=0.048).
UA therapy may prevent EIW after acute stroke in thrombolysed patients. Optimal access of UA to its molecular targets through appropriate collaterals may modify the magnitude of the neuroprotective effect.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00860366.
确定急性缺血性卒中的神经保护疗法势在必行。我们报告了对URICO-ICTUS试验（尿酸与重组组织型纤溶酶原激活剂联合治疗急性缺血性卒中的疗效研究）的一项预定义分析，评估尿酸（UA）与安慰剂相比预防早期缺血性恶化（EIW）的疗效以及侧支循环的相关性。
URICO-ICTUS是一项双盲、安慰剂对照的2b期试验，共有411例在卒中发作4.5小时内接受阿替普酶治疗的患者被随机（1:1）分配，在阿替普酶输注结束前接受1000mg UA（n = 211）或安慰剂（n = 200）。EIW定义为在无出血或复发性卒中的情况下，治疗72小时内美国国立卫生研究院卒中量表评分增加≥4分。逻辑回归模型评估了112例治疗前进行计算机断层血管造影的患者中治疗与侧支循环之间的相互作用。
149例（1%）预后良好的患者中有2例发生EIW，262例（9%）预后不良的患者中有23例发生EIW（χ；P = 0.002）。204例接受UA治疗的患者中有7例（3%）发生EIW，200例接受安慰剂治疗的患者中有18例（9%）发生EIW（χ；P = 0.01）。UA预防EIW的疗效与侧支循环之间存在显著相互作用（P = 0.029），与安慰剂相比，接受UA治疗且侧支循环良好的患者发生率较低（分别为2%和15%；P = 0.048）。
UA治疗可能预防溶栓患者急性卒中后的EIW。通过适当的侧支循环使UA最佳地作用于其分子靶点可能会改变神经保护作用的程度。
