School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
Health Technol Assess. 2013;17(1):v-vi, 1-188. doi: 10.3310/hta17010.
Current practice for suspected acute coronary syndrome (ACS) involves troponin testing 10-12 hours after symptom onset to diagnose myocardial infarction (MI). Patients with a negative troponin can be investigated further with computed tomographic coronary angiography (CTCA) or exercise electrocardiography (ECG).
We aimed to estimate the diagnostic accuracy of early biomarkers for MI, the prognostic accuracy of biomarkers for major adverse cardiac adverse events (MACEs) in troponin-negative patients, the diagnostic accuracy of CTCA and exercise ECG for coronary artery disease (CAD) and the prognostic accuracy of CTCA and exercise ECG for MACEs in patients with suspected ACS. We then aimed to estimate the cost-effectiveness of using alternative biomarker strategies to diagnose MI, and using biomarkers, CTCA and exercise ECG to risk-stratify troponin-negative patients.
We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations; Cumulative Index of Nursing and Allied Health Literature (CINAHL), EMBASE, Web of Science, Cochrane Central Database of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), NHS Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment database from 1985 (CTCA review) or 1995 (biomarkers review) to November 2010, reviewed citation lists and contacted experts to identify relevant studies.
Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool and prognostic studies using a framework adapted for the project. Meta-analysis was conducted using bayesian Markov chain Monte Carlo simulation. We developed a decision-analysis model to evaluate the cost-effectiveness of alternative biomarker strategies to diagnose MI, and the cost-effectiveness of biomarkers, CTCA or exercise ECG to risk-stratify patients with a negative troponin. Strategies were applied to a theoretical cohort of patients with suspected ACS. Cost-effectiveness was estimated as the incremental cost per quality-adjusted life-year (QALY) of each strategy compared with the next most effective, taking a health-service perspective and a lifetime horizon.
Sensitivity and specificity (95% predictive interval) were 77% (29-96%) and 93% (46-100%) for troponin I, 80% (33-97%) and 91% (53-99%) for troponin T (99th percentile threshold), 81% (50-95%) and 80% (26-98%) for quantitative heart-type fatty acid-binding protein (H-FABP), 68% (11-97%) and 92% (20-100%) for qualitative H-FABP, 77% (19-98%) and 39% (2-95%) for ischaemia-modified albumin and 62% (35-83%) and 83% (35-98%) for myoglobin. CTCA had 94% (61-99%) sensitivity and 87% (16-100%) specificity for CAD. Positive CTCA and positive-exercise ECG had relative risks of 5.8 (0.6-24.5) and 8.0 (2.3-22.7) for MACEs. In most scenarios in the economic analysis presentation, high-sensitivity troponin measurement was the most effective strategy with an incremental cost-effectiveness ratio (ICER) of less than the £20,000-30,000/QALY threshold (ICER £7487-17,191/QALY). CTCA appeared to be the most cost-effective strategy for patients with a negative troponin, with an ICER of £11,041/QALY. However, when a lower MACE rate was assumed, CTCA had a high ICER (£262,061/QALY) and the no-testing strategy was optimal.
There was substantial variation between the primary studies and heterogeneity in their results. Findings of the economic model were dependent on assumptions regarding the value of detecting and treating positive cases.
Although presentation troponin has suboptimal sensitivity, measurement of a 10-hour troponin level is unlikely to be cost-effective in most scenarios compared with a high-sensitivity presentation troponin. CTCA may be a cost-effective strategy for troponin-negative patients, but further research is required to estimate the effect of CTCA on event rates and health-care costs.
The National Institute for Health Research Health Technology Assessment programme.
目前对于疑似急性冠状动脉综合征（ACS）的治疗方法为发病后 10-12 小时进行肌钙蛋白检测以诊断心肌梗死（MI）。肌钙蛋白阴性的患者可以进一步通过计算机断层扫描冠状动脉造影（CTCA）或运动心电图检查。
我们旨在评估早期生物标志物对 MI 的诊断准确性、阴性肌钙蛋白患者的生物标志物对主要心脏不良事件（MACE）的预后准确性、CTCA 和运动心电图对冠心病（CAD）的诊断准确性以及 CTCA 和运动心电图对疑似 ACS 患者的 MACE 的预后准确性。然后，我们旨在评估替代生物标志物策略诊断 MI 的成本效益，以及使用生物标志物、CTCA 和运动心电图对阴性肌钙蛋白患者进行风险分层的成本效益。
我们检索了 MEDLINE、MEDLINE In-Process & Other Non-Indexed Citations； Cumulative Index of Nursing and Allied Health Literature（CINAHL）、EMBASE、Web of Science、Cochrane Central Database of Controlled Trials（CENTRAL）、Cochrane Database of Systematic Reviews（CDSR）、NHS Database of Abstracts of Reviews of Effects（DARE）和 Health Technology Assessment 数据库（CTCA 综述）或 1995 年（生物标志物综述）至 2010 年 11 月，审查了引文列表并联系了专家以确定相关研究。
使用 QUADAS 工具评估诊断研究，使用适应项目的框架评估预后研究。使用贝叶斯马尔可夫链蒙特卡罗模拟进行荟萃分析。我们开发了一个决策分析模型，以评估替代生物标志物策略诊断 MI 的成本效益，以及生物标志物、CTCA 或运动心电图对阴性肌钙蛋白患者进行风险分层的成本效益。该策略应用于疑似 ACS 的理论患者队列。从卫生服务角度和终身视角出发，将每个策略相对于下一个最有效的策略的增量成本效益比（每增加一个质量调整生命年的成本）作为成本效益的衡量标准。
肌钙蛋白 I 的敏感性和特异性（95%预测区间）分别为 77%（29-96%）和 93%（46-100%），肌钙蛋白 T（99%百分位阈值）为 80%（33-97%）和 91%（53-99%），定量心脏型脂肪酸结合蛋白（H-FABP）为 81%（50-95%）和 80%（26-98%），定性 H-FABP 为 68%（11-97%）和 92%（20-100%），缺血修饰白蛋白为 77%（19-98%）和 39%（2-95%），肌红蛋白为 62%（35-83%）和 83%（35-98%）。CTCA 对 CAD 的敏感性为 94%（61-99%），特异性为 87%（16-100%）。阳性 CTCA 和阳性运动心电图对 MACE 的相对风险分别为 5.8（0.6-24.5）和 8.0（2.3-22.7）。在经济分析演示的大多数情况下，高敏肌钙蛋白检测是最有效的策略，增量成本效益比（ICER）低于 20,000-30,000 英镑/QALY 阈值（ICER 为 7487-17191 英镑/QALY）。对于肌钙蛋白阴性的患者，CTCA 似乎是最具成本效益的策略，其增量成本效益比（ICER）为 11041 英镑/QALY。然而，当假设较低的 MACE 发生率时，CTCA 的 ICER 很高（262061 英镑/QALY），此时不进行检测的策略为最佳选择。
主要研究之间存在很大差异，结果存在异质性。经济模型的结果取决于对阳性病例检测和治疗价值的假设。
尽管目前的肌钙蛋白检测的敏感性欠佳，但与高敏肌钙蛋白检测相比，检测时间为 10 小时的肌钙蛋白检测不太可能在大多数情况下具有成本效益。对于肌钙蛋白阴性的患者，CTCA 可能是一种具有成本效益的策略，但需要进一步研究来评估 CTCA 对事件发生率和医疗保健成本的影响。
英国国家卫生研究院卫生技术评估计划。
