Carson Peter, Teerlink John R, Komajda Michel, Anand Inder, Packer Milton, Butler Javed, Doehner Wolfram, Ferreira João Pedro, Filippatos Gerasimos, Haass Markus, Miller Alan, Pehrson Steen, Pocock Stuart J, Iwata Tomoko, Brueckmann Martina, Gasior Tomasz, Zannad Faiez, Anker Stefan D
Rehoboth Beach, Delaware, USA.
Section of Cardiology, San Francisco Veterans Affairs Medical Center, School of Medicine, UCSF Medical Center, San Francisco, California, USA.
JACC Heart Fail. 2025 May;13(5):710-721. doi: 10.1016/j.jchf.2024.10.021. Epub 2025 Jan 29.
There is limited published information on outcome adjudication in heart failure (HF) trials, particularly in heart failure with preserved ejection fraction (HFpEF).
The study sought to compare investigator reports with clinical events committee (CEC) adjudication and assess the impact of the SCTI (Standardized Data Collection for Cardiovascular Trials) criteria.
In the EMPEROR-Preserved (EMPagliflozin outcome tRial in Patients with chronic heart Failure With Preserved Ejection Fraction) trial, we compared investigator reports with CEC for concordance, treatment effect on primary composite outcome events and components (first event primary heart failure hospitalization [HHF] or cardiovascular [CV] mortality), prognosis after first HHF, total HHF, and trial duration with and without SCTI criteria.
The CEC confirmed 67.4% investigator-reported events for the primary outcome (CV mortality 82.7%, HHF 66.3%). The HR for treatment effect did not differ between adjudication methods for the primary outcome: investigator reports (HR: 0.77; 95% CI: 0.69-0.87), CEC (HR: 0.79; 95% CI: 0.69-0.90), its components, or total HHFs. The prognosis after the first HHF for all-cause mortality and CV mortality also did not differ between investigator reports and the CEC, nor did investigator reports and HHFs with a different CEC cause. SCTI criteria were present in 92% of CEC HHFs with a similar treatment effect to non-SCTI criteria. The investigator-reported primary events reached the protocol target number 6 months earlier than the CEC (7 months with full SCTI criteria).
Investigator adjudication is an alternative to a CEC with similar accuracy and faster event accumulation in HFpEF. The use of granular (SCTI) criteria did not improve trial performance. Our data suggest that a broader definition of an HHF event could be particularly beneficial in HFpEF clinical trials. (EMPagliflozin outcome tRial in Patients with chronic heart Failure With Preserved Ejection Fraction; NCT03057951).
关于心力衰竭（HF）试验中结局判定的已发表信息有限，尤其是在射血分数保留的心力衰竭（HFpEF）方面。
本研究旨在比较研究者报告与临床事件委员会（CEC）的判定结果，并评估标准化心血管试验数据收集（SCTI）标准的影响。
在EMPEROR-Preserved（射血分数保留的慢性心力衰竭患者恩格列净结局试验）试验中，我们比较了研究者报告与CEC在一致性、对主要复合结局事件及其组成部分（首次原发性心力衰竭住院[HHF]或心血管[CV]死亡）的治疗效果、首次HHF后的预后、HHF总数以及有无SCTI标准时的试验持续时间等方面的差异。
CEC确认了研究者报告的67.4%的主要结局事件（CV死亡率为82.7%，HHF为66.3%）。主要结局的治疗效果风险比在两种判定方法之间无差异：研究者报告（风险比：0.77；95%置信区间：0.69 - 0.87），CEC（风险比：0.79；95%置信区间：0.69 - 0.90），其组成部分或HHF总数。研究者报告与CEC之间，首次HHF后全因死亡率和CV死亡率的预后也无差异，研究者报告与不同CEC病因的HHF之间也无差异。92%的CEC判定的HHF存在SCTI标准，其治疗效果与非SCTI标准相似。研究者报告的主要事件比CEC提前6个月达到方案规定的目标数量（完全符合SCTI标准时为7个月）。
在HFpEF中，研究者判定是CEC判定的一种替代方法，具有相似的准确性且事件积累更快。使用详细的（SCTI）标准并未改善试验表现。我们的数据表明，对HHF事件进行更宽泛的定义在HFpEF临床试验中可能特别有益。（射血分数保留的慢性心力衰竭患者恩格列净结局试验；NCT03057951）
