Division of Thoracic and Cardiovascular Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Ann Thorac Surg. 2012 Dec;94(6):1908-13. doi: 10.1016/j.athoracsur.2012.05.027. Epub 2012 Jul 12.
Coronary revascularization trials often use a composite endpoint of major adverse cardiac and cerebrovascular events (MACCE). The usual practice in analyzing data with a composite endpoint is to assign equal weights to each of the individual MACCE elements. Noninferiority margins are used to offset effects of presumably less important components, but their magnitudes are subject to bias. This study describes the relative importance of MACCE elements from a patient perspective.
A discrete choice experiment was conducted. Survey respondents were presented with a scenario that would make them eligible for the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) trial three-vessel disease cohort. Respondents chose among pairs of procedures that differed on the 3-year probability of MACCE, potential for increased longevity, and procedure/recovery time. Conjoint analysis derived relative weights for these attributes.
In all, 224 respondents completed the survey. The attributes did not have equal weight. Risk of death was most important (relative weight 0.23), followed by stroke (0.18), potential increased longevity and recovery time (each 0.17), myocardial infarction (0.14), and risk of repeat revascularization (0.11). Applying these weights to the SYNTAX 3-year endpoints resulted in a persistent, but decreased margin of difference in MACCE favoring coronary artery bypass graft surgery compared to percutaneous coronary intervention. When labeled only as "procedure A" and "procedure B," 87% of respondents chose coronary artery bypass graft surgery over percutaneous coronary intervention. When procedures were labeled as "coronary stent" and "coronary bypass surgery," only 73% chose coronary artery bypass graft surgery. Procedural preference varied with demographics, sex, and familiarity with the procedures.
The MACCE elements do not carry equal weight in a composite endpoint, from a patient perspective. Using a weighted composite endpoint increases the validity of statistical analyses and trial conclusions. Patients are subject to bias by labels when considering coronary revascularization.
冠状动脉血运重建试验常采用主要不良心脑血管事件（MACCE）的复合终点。分析复合终点数据时，通常对各MACCE 元素赋予相同权重。非劣效性界值用于抵消假定不太重要成分的影响，但界值大小存在偏倚。本研究从患者角度描述 MACCE 元素的相对重要性。
进行了一项离散选择实验。调查对象被提供一个符合 SYNTAX 试验三血管病变队列入组标准的场景。调查对象在两组不同 MACCE 发生概率、潜在生存获益和手术/康复时间的治疗方案中进行选择。联合分析得出这些属性的相对权重。
共有 224 名调查对象完成了调查。各属性的权重并不相等。死亡风险最重要（相对权重 0.23），其次是卒中（0.18）、潜在生存获益和康复时间（各 0.17）、心肌梗死（0.14）和再次血运重建风险（0.11）。将这些权重应用于 SYNTAX 3 年终点，结果显示与经皮冠状动脉介入治疗相比，冠状动脉旁路移植术更具优势，且优势持续存在，但 MACCE 差异缩小。当仅标记为“方案 A”和“方案 B”时，87%的调查对象选择冠状动脉旁路移植术而非经皮冠状动脉介入治疗。当方案被标记为“冠状动脉支架”和“冠状动脉旁路手术”时，仅有 73%的调查对象选择冠状动脉旁路移植术。手术偏好随人口统计学特征、性别和对手术的熟悉程度而变化。
从患者角度来看，复合终点的 MACCE 元素的权重并不相等。使用加权复合终点可提高统计分析和试验结论的有效性。在考虑冠状动脉血运重建时，患者会受到标签的影响而产生偏倚。
