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Comparing Analytical Methods for Composite Endpoints in Clinical Trials: Insights from the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) Trial.
Westerhout, Cynthia M; Rathwell, Sarah; Anstrom, Kevin J; Hernandez, Adrian F; Ponikowski, Piotr; Ezekowitz, Justin A; Voors, Adriaan A; Felker, G Michael; Bakal, Jeffrey A; Blaustein, Robert O; Nkulikiyinka, Richard; O'Connor, Christopher M; Armstrong, Paul W.
Afiliación
  • Westerhout CM; Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
  • Rathwell S; Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
  • Anstrom KJ; Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
  • Hernandez AF; Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA; Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA.
  • Ponikowski P; Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland.
  • Ezekowitz JA; Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
  • Voors AA; Department of Cardiology, University of Groningen, University Medical Center of Groningen, the Netherlands.
  • Felker GM; Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA; Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA.
  • Bakal JA; Alberta Health Services, Edmonton, Alberta, Canada.
  • Blaustein RO; Merck & Co., Inc., Whippany, New Jersey, USA.
  • Nkulikiyinka R; Bayer, Wuppertal, Germany.
  • O'Connor CM; Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA; Inova Heart and Vascular Institute, Falls Church, Virginia, USA.
  • Armstrong PW; Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada. Electronic address: paul.armstrong@ualberta.ca.
J Card Fail ; 2024 Aug 23.
Article en En | MEDLINE | ID: mdl-39182825
ABSTRACT
BACKGROUND AND

AIMS:

In the VICTORIA trial of participants with heart failure (HF) and reduced ejection fraction, vericiguat (V) reduced the primary composite outcome [time to first HF hospitalization (HFH) or cardiovascular death (CVD)] (897 events) compared to placebo (P) (972 events) (hazard ratio, 0.90; 95% confidence interval [CI], 0.82-0.98; p=0.02). In this prespecified secondary analysis, we applied the weighted composite endpoint (WCE) and the win ratio (WR) methods to provide complementary assessments of treatment effect. METHODS AND

RESULTS:

The WCE method estimated the mean HFH-adjusted survival based on prespecified weights from a Delphi panel of the VICTORIA executive committee and national leaders mild (weight per event 0.39), moderate (0.5) or severe (0.67) HFH, and CVD (1.0). The unmatched WR was estimated for the descending hierarchy of CVD, then recurrent HFH. The WCE used all 3412 primary clinical events 875(V416/P459) severe HFH, 1614(767/847) moderate HFH and 68(38/30) mild HFH, 855(414/441) CVD. Improved HFH-adjusted survival occurred with vericiguat [mean 78.2% vs. 75.6%; difference (95% CI) 2.4% (1.7%-3.2%); p<0.0001]. Based on the comparison of 6,375,624 pairs, the WR of 1.13 (95% CI, 1.03-1.24, p=0.01) also indicated improved clinical outcomes with vericiguat.

CONCLUSIONS:

The results of the WCE and WR methods were consistent with the primary analysis of the time to first HFH or CVD. Whereas both WCE and WR assessed recurrent events, the WCE allowed inclusion of all recurrent events, insights on the severity of HFH events, and an absolute measure of the participant-treatment experience. This approach complements conventional assessment, better informing consumers of new therapeutics and future trial designs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Card Fail Asunto de la revista: CARDIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Card Fail Asunto de la revista: CARDIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos