Allina Health Neuroscience, Spine, and Pain Institute, Minneapolis, MN, USA.
Allina Health Clinical Research Informatics and Analytics Team, Minneapolis, MN, USA.
Nutr Metab Cardiovasc Dis. 2023 Dec;33(12):2440-2443. doi: 10.1016/j.numecd.2023.07.028. Epub 2023 Jul 22.
Stroke is a major cause of mortality and disability, highlighting the importance of prevention. Clinical trials play an important role in evaluating interventions that can maximize stroke prevention. Traditional composite endpoints (TCE) used in clinical trials have limitations, as they pool together events of varying clinical importance. Weighted composite endpoints (WCE) have emerged as a solution to address these limitations and provide more accurate assessments of outcomes. In this study, we investigate the use of WCE in a previously reported negative clinical trial for stroke prevention.
We analyzed data from the Vitamin Intervention for Stroke Prevention (VISP) trial, which compared high dose and low dose multivitamin therapy. We utilized weighted methods to analyze time-to-event outcomes with censoring. The primary outcomes of interest were time to nonfatal stroke, nonfatal coronary events, and death. We calculated modified Kaplan-Meier (KM) curves for each intervention group. We also performed a modified log-rank test to assess significant differences based on the weighted KM curves. The analysis included 3668 VISP trial participants, and most remained event-free throughout the study period. The TCE KM curve showed no significant difference in outcomes between high dose and low dose groups. Similarly, the WCE KM curves, with different weights assigned to each outcome, did not reveal significant differences in outcomes between the studied groups.
This post-hoc analysis confirms the negative trial results of VISP and demonstrates the feasibility of using WCE in assessing nutrition-based interventions for stroke prevention.
中风是导致死亡和残疾的主要原因，凸显了预防的重要性。临床试验在评估可最大限度预防中风的干预措施方面发挥着重要作用。临床试验中使用的传统复合终点（TCE）存在局限性，因为它们将具有不同临床重要性的事件汇集在一起。加权复合终点（WCE）已成为解决这些局限性并更准确评估结果的一种方法。在这项研究中，我们研究了在一项先前报道的中风预防阴性临床试验中使用 WCE。
我们分析了维生素干预预防中风试验（VISP）的数据，该试验比较了高剂量和低剂量多种维生素治疗。我们使用加权方法分析了带有删失的时间至事件结果。主要关注的结局是无致命性中风、非致命性冠心病事件和死亡的时间。我们为每个干预组计算了修正的 Kaplan-Meier（KM）曲线。我们还进行了修正的对数秩检验，根据加权 KM 曲线评估显著差异。该分析包括 3668 名 VISP 试验参与者，在整个研究期间，大多数人仍然没有发生事件。TCE KM 曲线显示高剂量和低剂量组之间的结局没有显著差异。同样，为每个结局分配不同权重的 WCE KM 曲线也没有显示研究组之间的结局有显著差异。
这项事后分析证实了 VISP 试验的阴性结果，并表明在评估基于营养的中风预防干预措施时使用 WCE 的可行性。
