Portal de investigação
The win ratio method in heart failure trials: lessons learnt from EMPULSE
Data de publicação:
Data Ahead of Print:
Autores da FMUP
Participantes de fora da FMUP
- Pocock, SJ
- Collier, TJ
- Angermann, CE
- Biegus, J
- Collins, SP
- Kosiborod, M
- Nassif, ME
- Ponikowski, P
- Psotka, MA
- Teerlink, JR
- Tromp, J
- Gregson, J
- Blatchford, JP
- Zeller, C
- Voors, AA
Unidades de investigação
Abstract
Aims The EMPULSE trial evaluated the clinical benefit of empagliflozin versus placebo using the stratified win ratio approach in 530 patients with acute heart failure (HF) after initial stabilization. We aim to elucidate how this method works and what it means, thereby giving guidance for use of the win ratio in future trials.Methods and results The primary trial outcome is a hierarchical composite of death, number of HF events, time to first HF event, or a =5-point difference in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score change at 90 days. In an overall (unstratified) analysis we show how comparison of all 265 x 265 patients pairs contribute to 'wins' for empagliflozin and placebo at all four levels of the hierarchy, leading to an unstratified win ratio of 1.38 (95% confidence interval [CI] 1.11-1.71; p = 0.0036). How such a win ratio should (and should not) be interpreted is then described. The more complex primary analysis using a stratified win ratio is then presented in detail leading to a very similar overall result. Win ratios for de novo acute HF and decompensated chronic HF patients were 1.29 and 1.39, respectively, their weighted combination yielding an overall stratified win ratio of 1.36 (95% CI 1.09-1.68) (p = 0.0054). Alternative ways of including HF events and KCCQ scores in the clinical hierarchy are presented, leading to recommendations for their use in future trials. Specifically, inclusion of both number of HF events and time-to-first HF event appears an unnecessary complication. Also, the use of a 5-point margin for KCCQ score paired comparisons is not statistically necessary.Conclusions The EMPULSE trial findings illustrate how deaths, clinical events and patient-reported outcomes can be integrated into a win ratio analysis strategy that yields clinically meaningful findings of patient benefit. This has implications for future trial designs that recognize the clinical priorities of patient evaluation and the need for efficient progress towards approval of new treatments.
Dados da publicação
- ISSN/ISSNe:
- 1388-9842, 1879-0844
- Tipo:
- Article
- Páginas:
- 632-641
- DOI:
- 10.1002/ejhf.2853
- Link para outro recurso:
- www.scopus.com
European Journal of Heart Failure Wiley-Blackwell
Citações Recebidas na Web of Science: 4
Citações Recebidas na Scopus: 16
Documentos
- Não há documentos
Filiações
Keywords
- Win ratio; Clinical priorities; Hierarchical composite outcome; EMPULSE; Heart failure
Financiamento
Proyectos asociados
Dapagliflozin, Spironolactone or Both for HFpEF (SOGALDI-PEF) - NCT05676684
Investigador Principal: João Pedro Melo Marques Pinho Ferreira
Ensaio Clínico Académico (SOGALDI-PEF) . AstraZeneca . 2022
Citar a publicação
Pocock SJ,Ferreira JP,Collier TJ,Angermann CE,Biegus J,Collins SP,Kosiborod M,Nassif ME,Ponikowski P,Psotka MA,Teerlink JR,Tromp J,Gregson J,Blatchford JP,Zeller C,Voors AA. The win ratio method in heart failure trials: lessons learnt from EMPULSE. Eur. J. Heart Fail. 2023. 25. (5):p. 632-641. IF:18,200. (1).
