Cilostazol for Secondary Stroke Prevention: History, Evidence, Limitations, and Possibilities.
Cilostazol for Secondary Stroke Prevention: History, Evidence, Limitations, and Possibilities.
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DOI：
10.1161/strokeaha.121.035002
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发表时间：
2021-10
期刊：
影响因子：
8.3
通讯作者：
Lansberg MG
中科院分区：
文献类型：
--
作者：
de Havenon A;Sheth KN;Madsen TE;Johnston KC;Turan TN;Toyoda K;Elm JJ;Wardlaw JM;Johnston SC;Williams OA;Shoamanesh A;Lansberg MG
西洛他唑是一种磷酸二酯酶III抑制剂，具有长期的安全性记录，FDA和EMA批准用于治疗外周动脉疾病患者的跛行。此外，西洛他唑已经在几个亚洲国家被批准用于二级中风预防，这是基于试验表明，在非心源性中风患者中，西洛他唑可以减少中风复发。受益出现在治疗60-90天后，这与西洛他唑在血小板聚集、血管重塑、血流和血脂方面的多效性作用一致。西洛他唑似乎是安全的，单独给药或与阿司匹林或氯吡格雷合用时不会增加大出血的风险。然而，在一项大型二级中风预防试验(CSPS.com)中，在随机服用西洛他唑的患者中，头痛、胃肠道症状和心悸等不良反应导致停药人数增加6%。由于先前试验的局限性，如开放标签设计、试验过早终止、大量随访损失、缺乏功能或认知结果数据以及亚洲独家登记，现有试验并未导致西方国家的临床实践或指南发生变化。这些局限性可以通过在更广泛的人群中进行的双盲安慰剂对照随机试验来解决。如果呈阳性，这将增加支持西洛他唑对全世界数百万患有非心源性缺血性中风的患者进行二级预防的长期治疗的证据。
Cilostazol is a phosphodiesterase III inhibitor with a long track record of safety that is FDA and EMA approved for the treatment of claudication in patients with peripheral arterial disease. In addition, cilostazol has been approved for secondary stroke prevention in several Asian countries based on trials that have demonstrated a reduction in stroke recurrence among patients with non-cardioembolic stroke. The onset of benefit appears after 60–90 days of treatment, which is consistent with cilostazol’s pleiotropic effects on platelet aggregation, vascular remodeling, blood flow, and plasma lipids. Cilostazol appears safe and does not increase the risk of major bleeding when given alone or in combination with aspirin or clopidogrel. Adverse effects such as headache, gastrointestinal symptoms and palpitations, however, contributed to a 6% increase in drug discontinuation among patients randomized to cilostazol in a large secondary stroke prevention trial (CSPS.com). Due to limitations of prior trials, such as open label design, premature trial termination, large loss to follow-up, lack of functional or cognitive outcome data, and exclusive enrollment in Asia, the existing trials have not led to a change in clinical practice or guidelines in Western countries. These limitations could be addressed by a double-blind placebo-controlled randomized trial conducted in a broader population. If positive, it would increase the evidence in support of long-term treatment with cilostazol for secondary prevention in the millions of patients worldwide who have suffered a non-cardioembolic ischemic stroke.