Centre for Clinical Brain Science, University of Edinburgh, United Kingdom (C.M., G.W.B., F.M.C., F.D.).
Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, United Kingdom (J.P.A., P.M.B.).
Stroke. 2020 Aug;51(8):2374-2385. doi: 10.1161/STROKEAHA.120.029454. Epub 2020 Jul 10.
Cilostazol, a phosphodiesterase 3' inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression.
A systematic review and meta-analysis of unconfounded randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or radiological small vessel disease lesion progression. Two reviewers searched for papers (January 1, 2019 to July 16, 2019) and extracted data. We calculated Peto odds ratios (ORs) and 95% CIs for recurrent ischemic, hemorrhagic stroke, death, adverse symptoms, with sensitivity analyses. The review is registered (CRD42018084742).
We included 20 randomized controlled trials (n=10 505), 18 in ischemic stroke (total n=10 449) and 2 in cognitive impairment (n=56); most were performed in Asia-Pacific countries. Cilostazol decreased recurrent ischemic stroke (17 trials, n=10 225, OR=0.68 [95% CI, 0.57-0.81]; <0.0001), hemorrhagic stroke (16 trials, n=9736, OR=0.43 [95% CI, 0.29-0.64]; =0.0001), deaths (OR=0.64 [95% CI, 0.49-0.83], <0.0009), systemic bleeding (n=8387, OR=0.73 [95% CI, 0.54-0.99]; =0.04), but increased headache and palpitations, compared with placebo, aspirin, or clopidogrel. Cilostazol reduced recurrent ischemic stroke more when given long (>6 months) versus short term without increasing hemorrhage, and in trials with larger proportions (>40%) of lacunar stroke. Data were insufficient to assess effects on cognition, imaging, functional outcomes, or tolerance.
Cilostazol appears effective for long-term secondary stroke prevention without increasing hemorrhage risk. However, most trials related to Asia-Pacific patients and more trials in Western countries should assess its effects on cognitive decline, functional outcome, and tolerance, particularly in lacunar stroke and other presentations of small vessel disease.
西洛他唑是一种磷酸二酯酶 3'抑制剂，在亚太国家用于预防中风，但在其他地方很少使用。除了抗血小板作用较弱外，它还能稳定内皮细胞，有助于髓鞘修复和星形胶质细胞-神经元能量转移，这些作用可能有益于预防小血管疾病的进展。
对西洛他唑预防中风、认知下降或放射学小血管疾病病变进展的无混杂随机对照试验进行系统评价和荟萃分析。两名审查员搜索了论文（2019 年 1 月 1 日至 2019 年 7 月 16 日）并提取了数据。我们计算了复发性缺血性、出血性中风、死亡、不良反应的 Peto 比值比（OR）和 95%置信区间（CI），并进行了敏感性分析。该综述已在 CRD42018084742 上注册。
我们纳入了 20 项随机对照试验（n=10505），18 项为缺血性中风（总 n=10449），2 项为认知障碍（n=56）；大多数试验在亚太国家进行。西洛他唑降低了复发性缺血性中风（17 项试验，n=10225，OR=0.68[95%CI，0.57-0.81]；<0.0001）、出血性中风（16 项试验，n=9736，OR=0.43[95%CI，0.29-0.64]；=0.0001）、死亡（OR=0.64[95%CI，0.49-0.83]，<0.0009）、全身性出血（n=8387，OR=0.73[95%CI，0.54-0.99]；=0.04），但与安慰剂、阿司匹林或氯吡格雷相比，头痛和心悸的发生率增加。与安慰剂相比，西洛他唑在长期（>6 个月）治疗时降低复发性缺血性中风的效果优于短期治疗，且在比例较大（>40%）的腔隙性中风患者中更为明显。数据不足以评估其对认知、影像学、功能结局或耐受性的影响。
西洛他唑似乎对长期二级中风预防有效，且不增加出血风险。然而，大多数与亚太地区患者相关的试验以及更多的西方国家试验应评估其对认知下降、功能结局和耐受性的影响，特别是在腔隙性中风和小血管疾病的其他表现中。
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