Ott Brian R, Daiello Lori A, Dahabreh Issa J, Springate Beth A, Bixby Kimberly, Murali Manjari, Trikalinos Thomas A
Rhode Island Hospital, Department of Neurology, Alpert Medical School of Brown University, Providence, RI, USA,
J Gen Intern Med. 2015 Mar;30(3):348-58. doi: 10.1007/s11606-014-3115-3. Epub 2015 Jan 10.
In 2012, the United States Food and Drug Administration (FDA) issued a warning regarding potential adverse effects of HMG-CoA reductase inhibitors (statins) on cognition, based on the Adverse Events Reporting System and a review of the medical literature. We aimed to synthesize randomized clinical trial (RCTs) evidence on the association between statin therapy and cognitive outcomes.
We searched MEDLINE, EMBASE, and Cochrane CENTRAL through December 2012, and reviewed published systematic reviews of statin treatment. We sought RCTs that compared statin treatment versus placebo or standard care, and reported at least one cognitive outcome (frequency of adverse cognitive events or measurements using standard neuropsychological cognitive test scores). Studies reporting sufficient information to calculate effect sizes were included in meta-analyses. Standardized and unstandardized mean differences were calculated for continuous outcomes for global cognition and for pre-specified cognitive domains. The main outcome was change in cognition measured by neuropsychological tests; an outcome of secondary interest was the frequency of adverse cognitive events observed during follow-up.
We identified 25 RCTs (all placebo-controlled) reporting cognitive outcomes in 46,836 subjects, of which 23 RCTs reported cognitive test results in 29,012 participants. Adverse cognitive outcomes attributable to statins were rarely reported in trials involving cognitively normal or impaired subjects. Furthermore, meta-analysis of cognitive test data (14 studies; 27,643 participants) failed to show significant adverse effects of statins on all tests of cognition in either cognitively normal subjects (standardized mean difference 0.01, 95% confidence interval, CI, -0.01 to 0.03, p = 0.42) or Alzheimer's disease subjects (standardized mean difference -0.05, 95% CI -0.19 to 0.10, p = 0.38).
Statin therapy was not associated with cognitive impairment in RCTs. These results raise questions regarding the continued merit of the FDA warning about potential adverse effects of statins on cognition.
2012年，美国食品药品监督管理局（FDA）基于不良事件报告系统及医学文献综述，发布了关于HMG-CoA还原酶抑制剂（他汀类药物）对认知功能潜在不良影响的警告。我们旨在综合随机临床试验（RCT）证据，以探讨他汀类药物治疗与认知结局之间的关联。
我们检索了截至2012年12月的MEDLINE、EMBASE和Cochrane CENTRAL，并查阅了已发表的关于他汀类药物治疗的系统评价。我们寻找比较他汀类药物治疗与安慰剂或标准治疗，并报告至少一项认知结局（不良认知事件的频率或使用标准神经心理学认知测试分数进行的测量）的RCT。报告了足够信息以计算效应量的研究纳入荟萃分析。计算了整体认知及预先指定的认知领域连续结局的标准化和非标准化平均差异。主要结局是通过神经心理学测试测量的认知变化；次要感兴趣的结局是随访期间观察到的不良认知事件的频率。
我们识别出25项RCT（均为安慰剂对照），报告了46,836名受试者的认知结局，其中23项RCT报告了29,012名参与者的认知测试结果。在涉及认知正常或受损受试者的试验中，很少报告他汀类药物导致的不良认知结局。此外，对认知测试数据的荟萃分析（14项研究；27,643名参与者）未能显示他汀类药物对认知正常受试者（标准化平均差异0.01，95%置信区间[CI]，-0.01至0.03，p = 0.42）或阿尔茨海默病受试者（标准化平均差异-0.05，95%CI -0.19至0.10，p = 0.38）的所有认知测试有显著不良影响。
在RCT中，他汀类药物治疗与认知损害无关。这些结果引发了关于FDA对他汀类药物对认知功能潜在不良影响的警告是否仍有价值的疑问。
