Assessment of Vascular Event Prevention and Cognitive Function Among Older Adults With Preexisting Vascular Disease or Diabetes A Secondary Analysis of 3 Randomized Clinical Trials
Assessment of Vascular Event Prevention and Cognitive Function Among Older Adults With Preexisting Vascular Disease or Diabetes A Secondary Analysis of 3 Randomized Clinical Trials
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DOI：
10.1001/jamanetworkopen.2019.0223
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发表时间：
2019-03-01
影响因子：
13.8
通讯作者：
Parish, Sarah
中科院分区：
文献类型：
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作者：
Offer, Alison;Arnold, Matthew;Parish, Sarah
重要性获取可靠的随机临床试验证据的影响，心血管干预对认知能力下降是一个优先事项。目的是估计相关的认知老化与避免血管事件的心血管干预试验，并了解是否报告的非显着结果排除有价值的好处。和参与者这项对3项随机临床试验的二次分析，受试者既存闭塞性血管疾病或糖尿病，包括心脏保护研究（HPS）中最终试验随访的幸存者，额外降低胆固醇和同型半胱氨酸（HDL-C）的有效性研究，以及HDL（高密度脂蛋白）治疗降低血管事件发生率（HPS 2-THRIVE）脂质修饰预防心血管事件的试验。数据收集自1994年2月至2013年1月，分析自2015年1月至2018年12月。主要结果和指标在平均（SD）4.9（1.5）年的随访结束时，使用14项语言测试评估认知功能。评估试验期间血管事件和新发糖尿病的发生率与最终试验期间随访时认知功能的相关性，并表示为认知老化年数（使用评分与年龄>60岁的相关性）。通过降低低密度脂蛋白胆固醇水平对事件的影响介导的认知老化的好处，估计通过应用这些研究结果与他汀类药物治疗HPS trial.Results中观察到的非致命性事件的差异在45029参与者进行认知评估，平均（SD）年龄为67.9（8.0）岁，80.7%是男性。卒中事件（n = 1197）与7.1（95%CI，5.7-8.5）年的认知老化相关;短暂性脑缺血发作、心肌梗死、心力衰竭和新发糖尿病事件与1 - 2年的认知老化相关。在HPS中，随机接受他汀类药物治疗5年，2.0%的幸存者避免了非致死性卒中或短暂性脑缺血发作，2.4%的幸存者避免了非致死性心脏事件，预期认知老化减少0.15（95%CI，0.11-0.19）年。与15 926名参与者进行认知评估，HPS有80%的权力来检测1年（即20%，在5年）的差异，在认知ageing.Conclusions和相关性的预期认知效益的影响，预防性治疗对心血管事件，即使是最大的随机临床试验可能已经太小，无法检测。因此，无意义的发现可能无法提供长期使用此类治疗对认知功能缺乏有价值益处的良好证据。
IMPORTANCE Acquisition of reliable randomized clinical trial evidence of the effects of cardiovascular interventions on cognitive decline is a priority.OBJECTIVES To estimate the association of cognitive aging with the avoidance of vascular events in cardiovascular intervention trials and understand whether reports of nonsignificant results exclude worthwhile benefit.DESIGN, SETTING, AND PARTICIPANTS This secondary analysis of 3 randomized clinical trials in participants with preexisting occlusive vascular disease or diabetes included survivors to final in-trial follow-up in the Heart Protection Study (HPS), Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), and Treatment of HDL (High-Density Lipoprotein) to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trials of lipid modification for prevention of cardiovascular events. Data were collected from February 1994 through January 2013 and analyzed from January 2015 through December 2018.EXPOSURES Incident vascular events and diabetes and statin therapy.MAIN OUTCOMES AND MEASURES Cognitive function was assessed at the end of a mean (SD) of 4.9 (1.5) years of follow-up using a 14-item verbal test. Associations of the incidence of vascular events and new-onset diabetes during the trials, with cognitive function at final in-trial follow-up were estimated and expressed as years of cognitive aging (using the association of the score with age >60 years). The benefit on cognitive aging mediated through the effects of lowering low-density lipoprotein cholesterol levels on events was estimated by applying these findings to nonfatal event differences observed with statin therapy in the HPS trial.RESULTS Among 45 029 participants undergoing cognitive assessment, mean (SD) age was 67.9 (8.0) years; 80.7% were men. Incident stroke (n = 1197) was associated with 7.1 (95% CI, 5.7-8.5) years of cognitive aging; incident transient ischemic attack, myocardial infarction, heart failure, and new-onset diabetes were associated with 1 to 2 years of cognitive aging. In HPS, randomization to statin therapy for 5 years resulted in 2.0% of survivors avoiding a nonfatal stroke or transient ischemic attack and 2.4% avoiding a nonfatal cardiac event, which yielded an expected reduction in cognitive aging of 0.15 (95% CI, 0.11-0.19) years. With 15 926 participants undergoing cognitive assessment, HPS had 80% power to detect a 1-year (ie, 20% during the 5 years) difference in cognitive aging.CONCLUSIONS AND RELEVANCE The expected cognitive benefits of the effects of preventive therapies on cardiovascular events during even the largest randomized clinical trials may have been too small to be detectable. Hence, nonsignificant findings may not provide good evidence of a lack of worthwhile benefit on cognitive function with prolonged use of such therapies.