Arbetter Douglas F, Jain Purva, Yee Megan K, Michalak Nathan, Hernandez Adrian F, Hull Russell D, Goldhaber Samuel Z, Harrington Robert A, Gold Alex, Cohen Alexander T, Gibson C Michael
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical Center, Boston, MA, USA.
Duke University and Duke Clinical Research Institute, Durham, NC, USA.
Pharm Stat. 2017 Nov;16(6):445-450. doi: 10.1002/pst.1823. Epub 2017 Aug 24.
Competing risk methods are time-to-event analyses that account for fatal and/or nonfatal events that may potentially alter or prevent a subject from experiencing the primary endpoint. Competing risk methods may provide a more accurate and less biased estimate of the incidence of an outcome but are rarely applied in cardiology trials. APEX investigated the efficacy of extended-duration betrixaban versus standard-duration enoxaparin to prevent a composite of symptomatic deep-vein thrombosis (proximal or distal), nonfatal pulmonary embolism, or venous thromboembolism (VTE)-related death in acute medically ill patients (n = 7513). The aim of the current analysis was to determine the efficacy of betrixaban vs standard-duration enoxaparin accounting for non-VTE-related deaths using the Fine and Gray method for competing risks. The proportion of non-VTE-related death was similar in both the betrixaban (133, 3.6%) and enoxaparin (136, 3.7%) arms, P = .85. Both the traditional Kaplan-Meier method and the Fine and Gray method accounting for non-VTE-related death as a competing risk showed equal reduction of VTE events when comparing betrixaban to enoxaparin (HR/SHR = 0.65, 95% 0.42-0.99, P = 0.046). Due to the similar proportion of non-VTE-related deaths in both treatment arms and the use of a univariate model, the Fine and Gray method provided identical results to the traditional Cox model. Using the Fine and Gray method in addition to the traditional Cox proportional hazards method can indicate whether the presence of a competing risk, which is dependent of the outcome, altered the risk estimate.
竞争风险方法是一种事件发生时间分析方法，用于考虑可能改变或阻止受试者经历主要终点的致命和/或非致命事件。竞争风险方法可能会提供更准确且偏差更小的结局发生率估计，但在心脏病学试验中很少应用。APEX研究了延长疗程的贝曲西班与标准疗程的依诺肝素在预防急性内科疾病患者（n = 7513）发生有症状的深静脉血栓形成（近端或远端）、非致命性肺栓塞或静脉血栓栓塞（VTE）相关死亡的复合结局方面的疗效。当前分析的目的是使用竞争风险的Fine和Gray方法确定贝曲西班与标准疗程依诺肝素在考虑非VTE相关死亡情况下的疗效。在贝曲西班组（133例，3.6%）和依诺肝素组（136例，3.7%）中，非VTE相关死亡的比例相似，P = 0.85。当比较贝曲西班与依诺肝素时，将非VTE相关死亡作为竞争风险的传统Kaplan-Meier方法和Fine和Gray方法均显示VTE事件有同等程度的减少（HR/SHR = 0.65，95% 0.42 - 0.99，P = 0.046）。由于两个治疗组中非VTE相关死亡的比例相似且使用了单变量模型，Fine和Gray方法提供了与传统Cox模型相同的结果。除传统的Cox比例风险方法外，使用Fine和Gray方法可以表明竞争风险（其取决于结局）的存在是否改变了风险估计。
