他汀类药物相关肌肉症状反安慰剂效应系统评价

Nocebo/Drucebo Effect of Statin-Associated Muscle Symptoms:A Systematic Review

目的系统评价他汀类药物相关肌肉症状(SAMS)的反安慰剂效应,为临床用药决策提供循证参考。方法采用计算机检索PubMed、Embase、中国知网、万方数据库中自建库起至2023年8月1日有关SAMS的文献,纳入比较了在盲法和非盲法阶段他汀类药物干预时肌肉相关不良事件的发生频率或强度差异、既往报告他汀类药物不耐受患者再激发试验基线期和盲法期的肌肉症状差异、在盲法阶段他汀类药物干预组和安慰剂对照组的肌肉症状不良事件发生频率或强度差异的随机对照试验(RCT)或单病例随机对照试验(N-of-1试验)。采用Cochrane偏倚风险评估工具RoB 2对纳入文献进行质量评价。根据各研究间的异质性选择对数据进行定量分析或定性描述,估算反安慰剂效应值。结果共检索到1229篇相关文献,最终纳入8项研究,其方法设计、结局指标和结果报告均存在异质性,故仅对结果进行定性描述。在他汀类药物治疗期间,约有38.00%~77.78%报告的SAMS或药物不耐受情况受到了反安慰剂效应的影响;SAMSON试验中反安慰剂比率为90%。结论正确识别和管理SAMS及其导致的药物不耐受现象,警惕反安慰剂效应对临床治疗决策的干扰,有利于提高患者降脂治疗的长期依从性,降低患者主要心血管不良事件的发生率及死亡率。

Objective To evaluate the nocebo/drucebo effect of statin-associated muscle symptoms(SAMS),and to provide evidence-based reference for clinical medication decision-making.Methods Literature related to SAMS in PubMed,Embase,CNKI,and WanFang databases was searched from the inception to August 1,2023,and the randomized controlled trials(RCTs)or N-of-1 trials of comparing the incidence or intensity differences of muscle-related adverse events(AEs)during the blinded and open-lable period of a statin intervention,comparing the difference of muscle symptoms during the baseline and the blinded phase of rechallenge trials in patients with previous statin intolerance,or comparing the incidence or intensity differences of muscle-related AEs between statin intervention and placebo during the blinded phase were included.The Cochrane Risk of Bias 2(RoB 2)tool was used to evaluate the quality of RCTs.The methods of data processing(quantitative analysis or qualitative description)were selected according to the heterogeneity among studies,and the nocebo/drucebo effect value was estimated.Results A total of 1229 relevant studies were searched and ultimately eight studies were included.Due to heterogeneity in the methodology design,outcome indicators,and outcome reports of the eight studies,only qualitative descriptions of the results were provided.Approximately 38.00%to 77.78%of reported SAMS or drug intolerance during statin therapy were affected by nocebo/drucebo effect,and the nocebo/drucebo ratio in the SAMSON trial was 90%.Conclusion Proper identification and management of SAMS and drug intolerance during statin therapy,as well as vigilance against nocebo/drucebo effect on making clinical decisions,will help to improve patients′long-term compliance with lipid-lowering therapy and reduce the incidence of major adverse cardiovascular events and mortality.