Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan.
Department of Internal Medicine, John H Stroger Jr Hospital of Cook County, Chicago, IL.
Am Heart J. 2020 Dec;230:71-81. doi: 10.1016/j.ahj.2020.09.001. Epub 2020 Sep 15.
Cardiovascular randomized controlled trials (RCTs) typically set composite end points as the primary outcome to enhance statistical power. However, influence of individual component end points on overall composite outcomes remains understudied.
We searched MEDLINE for RCTs published in 6 high-impact journals (The Lancet, the New England Journal of Medicine, Journal of the American Medical Association, Circulation, Journal of the American College of Cardiology and the European Heart Journal) from 2011 to 2017. Two-armed, parallel-design cardiovascular RCTs which reported composite outcomes were included. All-cause or cardiovascular mortality, myocardial infarction, heart failure, and stroke were deemed "hard" end points, whereas hospitalization, angina, and revascularization were identified as "soft" end points. Type of outcome (primary or secondary), event rates in treatment and control groups for the composite outcome and of its components according to predefined criteria.
Of the 45.8% (316/689) cardiovascular RCTs which used a composite outcome, 79.4% set the composite as the primary outcome. Death was the most common component (89.8%) followed by myocardial infarction (66.1%). About 80% of the trials reported complete data for each component. One hundred forty-seven trials (46.5%) incorporated a "soft" end point as part of their composite. Death contributed the least to the estimate of effects (R change = 0.005) of the composite, whereas revascularization contributed the most (R change = 0.423).
Cardiovascular RCTs frequently use composite end points, which include "soft" end points, as components in nearly 50% of studies. Higher event rates in composite end points may create a misleading interpretation of treatment impact due to large contributions from end points with less clinical significance.
心血管随机对照试验（RCT）通常将复合终点作为主要结局指标，以提高统计学效能。然而，单个终点指标对总体复合结局的影响仍研究不足。
我们检索了 2011 年至 2017 年在 6 种高影响力期刊（《柳叶刀》《新英格兰医学杂志》《美国医学会杂志》《循环》《美国心脏病学会杂志》和《欧洲心脏杂志》）上发表的 RCT，纳入了报告复合结局的双臂、平行设计的心血管 RCT。全因或心血管死亡率、心肌梗死、心力衰竭和卒中等被视为“硬终点”，而住院、心绞痛和血运重建则被定义为“软终点”。根据预先设定的标准，我们评估了结局类型（主要或次要）、复合结局及各组成部分在治疗组和对照组中的事件发生率。
在使用复合结局的 689 项心血管 RCT 中，45.8%（316/689）采用了复合结局，其中 79.4%将复合结局作为主要结局。死亡是最常见的组成部分（89.8%），其次是心肌梗死（66.1%）。约 80%的试验报告了每个组成部分的完整数据。147 项试验（46.5%）将“软终点”作为复合结局的一部分。死亡对复合结局效应的估计贡献最小（R 变化=0.005），而血运重建的贡献最大（R 变化=0.423）。
心血管 RCT 经常使用复合终点，其中近 50%的研究包含“软终点”作为组成部分。复合终点的事件发生率较高，可能会导致对治疗效果的误解，因为具有较少临床意义的终点对效应的贡献较大。
