Waugh N, Black C, Walker S, McIntyre L, Cummins E, Hillis G
Department of Public Health, University of Aberdeen, UK.
Health Technol Assess. 2006 Oct;10(39):iii-iv, ix-x, 1-41. doi: 10.3310/hta10390.
To assess the clinical and cost-effectiveness of computed tomography (CT) screening for asymptomatic coronary artery disease; also to establish whether coronary artery calcification (CAC) predicts coronary events and adds anything to risk factor scores, and whether measuring CAC changes treatment.
Main electronic databases were searched up to 2005, with a MEDLINE update in February 2006.
A systematic review of screening studies and economic evaluations was carried out. Studies were included in the review if screening for coronary heart disease was the principal theme of the study, and if data were provided that allowed comparison of CT screening with current practice, which was taken to be risk factor scoring. Mismatches between CAC scores and risk factor scoring were of particular interest. A review of the case for screening against the criteria used by the National Screening Committee (NSC) for assessing screening programmes was also undertaken.
No randomised control trials (RCTs) were found that assessed the value of CT screening in reducing cardiac events. Seven studies were identified that assessed the association between CAC scores on CT and cardiac outcomes in asymptomatic people and included 30,599 people. Six used electron-beam CT. The relative risk of a cardiac event was 4.4 if CAC was present, compared to there being no CAC. As CAC score increased, so did the risk of cardiac events. The correlation between CAC and cardiac risk was consistent across studies. There was evidence that CAC scores varied among people with the same Framingham risk factor scores, and that within the same Framingham bands, people with higher CAC scores had significantly higher cardiac event rates. This applied mainly when the CAC scores exceeded 300. There was little difference in event rates among the groups with no CAC, and scores of 1-100 and 101-300. In one study, CAC score was a better predictor of cardiac events than the Framingham risk scores. No studies were found that showed whether the addition of CAC scores to standard risk factor assessment would improve outcomes. There were reports from two observational studies that lowering of low-density lipoprotein cholesterol to about 3 mmol/l; or below with statin treatment modestly reduced CAC scores, but this was not confirmed in two RCTs. In three studies examining whether knowledge of CAC scores would affect compliance with lifestyle measures, perception of risk was affected, but it did not improve smoking cessation rates, although it did increase anxiety. There were a few economic studies of CT screening for heart disease, which provided useful data on costs of scans, other investigations and treatment, but relied on a number of assumptions, and were unable to provide definitive answers. One modelling study estimated that adding CT screening to risk factor scoring, and only giving statins to those with CAC score over 100, would save money, based on a cost per CT screen of US$400 and statin costs of US$1000 per annum per patient. However, the arrival of generic statins has reduced the price dramatically, and these savings no longer apply.
CT examination of the coronary arteries can detect calcification indicative of arterial disease in asymptomatic people, many of whom would be at low risk when assessed by traditional risk factors. The higher the CAC score, the higher the risk. Treatment with statins can reduce that risk. However, CT screening would miss many of the most dangerous patches of arterial disease, because they are not yet calcified, and so there would be false-negative results: normal CT followed by a heart attack. There would also be false-positive results in that many calcified arteries will have normal blood flow and will not be affected by clinically apparent thrombosis: abnormal CT not followed by a heart attack. For CT screening to be cost-effective, it has to add value over risk factor scoring, by producing sufficient additional information to change treatment and hence cardiac outcomes, at an affordable cost per quality-adjusted life-year. There was insufficient evidence to support this. Most of the NSC criteria were either not met or only partially met. It would be useful to have more data on the distributions of risk scores and CAC scores in asymptomatic people, and the level of concordance between risk factor and CAC scores, the risk of cardiac events per annum according to CAC score and risk factor scores, information on the acceptability of CT screening, after information about the radiation dose, and an RCT of adding CT screening to current risk factor-based practice.
评估计算机断层扫描(CT)筛查无症状冠状动脉疾病的临床效果及成本效益;确定冠状动脉钙化(CAC)是否能预测冠状动脉事件,是否能为风险因素评分增添信息,以及测量CAC是否会改变治疗方案。
检索主要电子数据库至2005年,并于2006年2月更新MEDLINE。
对筛查研究和经济评估进行系统综述。若冠心病筛查是研究的主要主题,且提供的数据能将CT筛查与当前做法(即风险因素评分)进行比较,则该研究纳入综述。尤其关注CAC评分与风险因素评分之间的差异。还依据国家筛查委员会(NSC)评估筛查项目所用标准,对筛查理由进行了综述。
未发现评估CT筛查在降低心脏事件方面价值的随机对照试验(RCT)。确定了7项评估CT上CAC评分与无症状人群心脏结局之间关联的研究,共纳入30599人。6项研究使用电子束CT。存在CAC时发生心脏事件的相对风险为4.4,而无CAC时为1。随着CAC评分增加,心脏事件风险也增加。各研究中CAC与心脏风险之间的相关性一致。有证据表明,具有相同弗雷明汉风险因素评分的人群中,CAC评分存在差异,且在相同的弗雷明汉分组内,CAC评分较高者心脏事件发生率显著更高。这主要适用于CAC评分超过300的情况。无CAC、评分1 - 100和101 - 300的组之间事件发生率差异不大。在一项研究中,CAC评分比弗雷明汉风险评分更能预测心脏事件。未发现研究表明在标准风险因素评估中加入CAC评分是否会改善结局。两项观察性研究报告称,他汀类药物治疗使低密度脂蛋白胆固醇降至约3 mmol/l或更低可适度降低CAC评分,但两项RCT未证实这一点。在三项研究是否知晓CAC评分会影响生活方式措施依从性的研究中,风险认知受到影响,但未提高戒烟率,尽管增加了焦虑。有几项关于CT筛查心脏病的经济研究,提供了扫描、其他检查和治疗成本的有用数据,但依赖诸多假设,无法给出明确答案。一项模型研究估计,基于每次CT筛查成本400美元及每位患者每年他汀类药物成本1000美元,在风险因素评分基础上增加CT筛查,且仅对CAC评分超过100者给予他汀类药物,可节省费用。然而,通用他汀类药物的出现大幅降低了价格,这些节省已不再适用。
冠状动脉CT检查可在无症状人群中检测到提示动脉疾病的钙化,其中许多人按传统风险因素评估处于低风险。CAC评分越高,风险越高。他汀类药物治疗可降低该风险。然而,CT筛查会遗漏许多最危险的动脉疾病斑块,因为它们尚未钙化,从而会出现假阴性结果:CT正常随后发生心脏病发作。也会有假阳性结果,即许多钙化动脉血流正常,不会受临床明显血栓形成影响:CT异常但未随后发生心脏病发作。要使CT筛查具有成本效益,必须在风险因素评分基础上增加价值,即通过以可承受的每质量调整生命年成本产生足够的额外信息来改变治疗方案,进而改善心脏结局。但证据不足,无法支持这一点。NSC的大多数标准未得到满足或仅部分得到满足。获取更多关于无症状人群风险评分和CAC评分分布、风险因素与CAC评分之间的一致性水平、根据CAC评分和风险因素评分每年发生心脏事件的风险、关于CT筛查可接受性的信息(在了解辐射剂量之后)以及将CT筛查添加到当前基于风险因素的实践中的RCT数据将很有帮助。