University of Southern California, Viterbi School of Engineering, Los Angeles (E.M.S.).
Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine, University of California Los Angeles (J.L.S.).
Stroke. 2024 Aug;55(8):2022-2033. doi: 10.1161/STROKEAHA.123.044071. Epub 2024 Jun 14.
Statin agents play a major role in secondary prevention after acute cerebral ischemia (ACI) events but are not indicated in all patients with ischemic stroke and transient ischemic attack. National guidelines recommend statins for patients with ACI of large or small vessel atherosclerotic origin and without these stroke mechanisms but coexisting coronary artery disease or primary prevention indications. The potential adverse effect burden of statin overuse in the remaining ACI patients have not been well delineated.
Per Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines, we performed systematic meta-analyses of: (1) statin randomized clinical trials to determine absolute risk increases for 6 major adverse events; (2) large clinical series to determine the proportion of ACI events due to large or small vessel atherosclerotic disease; and (3) the proportion of remaining patients with coronary artery disease/primary prevention statin indications.
For adverse effects, data were available from 63 randomized clinical trials enrolling 155 107 patients. Statin therapy was associated with an increased risk of the occurrence of 6 conditions: diabetes, myalgia or muscle weakness, myopathy, liver disease, renal insufficiency, and eye disease. Across 55 large series enrolling 53 501 patients, the rate of ACI due to large and small artery atherosclerosis was 45.0% (large artery atherosclerosis 21.6%, small vessel disease 23.4%), the rate of remaining patients with coronary artery disease/primary prevention statin indications was 31.8%, and the rate of patients without statin indications was 23.2%. Data synthesis indicated that, in the United States, were all patients with ACI without statin indications treated with statins, a total of 5601 patients would develop needless adverse events each year, most commonly diabetes, myopathy, and eye disease.
More than one-fifth of patients with ACI do not have an indication for statins, and statin overuse in these patients could annually lead to over 5600 adverse events each year in the United States, including diabetes, myopathy, and eye disease. These findings emphasize the importance of adhering to guideline indications for the start of statin therapy in ACI.
他汀类药物在急性脑缺血（ACI）事件后的二级预防中发挥着重要作用，但并非所有缺血性卒中和短暂性脑缺血发作患者都适用。国家指南建议将他汀类药物用于大或小血管动脉粥样硬化性起源的 ACI 患者，且无这些卒中机制，但同时伴有冠状动脉疾病或一级预防指征。他汀类药物在剩余 ACI 患者中过度使用的潜在不良影响负担尚未得到充分阐明。
根据系统评价和荟萃分析的首选报告项目，我们对以下内容进行了系统的荟萃分析：（1）他汀类药物随机临床试验，以确定 6 种主要不良事件的绝对风险增加；（2）大型临床系列，以确定由于大或小血管动脉粥样硬化性疾病导致的 ACI 事件的比例；（3）剩余具有冠状动脉疾病/一级预防他汀类药物指征的患者比例。
对于不良反应，有 63 项随机临床试验的数据可供 155107 名患者使用。他汀类药物治疗与 6 种疾病的发生风险增加相关：糖尿病、肌痛或肌肉无力、肌病、肝病、肾功能不全和眼病。在 55 项纳入 53501 名患者的大型系列研究中，由于大、小动脉粥样硬化导致的 ACI 发生率为 45.0%（大动脉粥样硬化 21.6%，小血管疾病 23.4%），剩余具有冠状动脉疾病/一级预防他汀类药物指征的患者发生率为 31.8%，无他汀类药物指征的患者发生率为 23.2%。数据综合表明，在美国，如果所有没有他汀类药物指征的 ACI 患者都接受他汀类药物治疗，每年将有 5601 名患者会出现不必要的不良反应，最常见的是糖尿病、肌病和眼病。
超过五分之一的 ACI 患者没有使用他汀类药物的指征，在这些患者中过度使用他汀类药物每年可能导致美国每年超过 5600 例不良事件，包括糖尿病、肌病和眼病。这些发现强调了在 ACI 中遵循指南开始他汀类药物治疗指征的重要性。
