{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T18:37:06Z","timestamp":1772044626786,"version":"3.50.1"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":149,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Merck Sharp & Dohme LLC"},{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Heterogeneity in demographics, aetiology, healthcare access and guideline-directed medical therapy (GDMT), and survival bias of patients with heart failure with reduced ejection fraction (HFrEF) is evident from international trials and registries. The current study examines conventional geographic variation in participants' phenotypes, standard of care, clinical outcomes and treatment effects of vericiguat versus placebo within the VICTORIA trial. We then evaluate an alternative approach to assessing the relationship between geographic variation in the efficacy of new therapeutics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Characteristics, standard of care and outcomes (time to first HF hospitalization (HFH) or cardiovascular death (CVD), time to first HFH and to CVD) of the 5050 participants from 42 countries and the effect of vericiguat versus placebo were analysed according to five prespecified geographic regions. Further examination of the study treatment effect according to country-level human development index (HDI) was undertaken to evaluate intra-regional variation. Notable inter-region differences existed in participant characteristics, standard of care at randomization and clinical outcomes. There was no modification of vericiguat's treatment benefit across geographic regions for the primary composite endpoint or its components. When examined by HDI, vericiguat's benefit on HFH and the primary composite was retained overall but attenuated as HDI rose (Pinteraction = 0.009, 0.088, respectively). There was no apparent treatment effect modification due to HDI on cardiovascular death (Pinteraction = 0.623).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Geographic variation in the phenotype of patients with HFrEF, standard of care, and clinical outcomes was observed, while there was no intra-regional heterogeneity in vericiguat's treatment effect. However, when considering contextual\/systemic measures via country-level HDI, further insights into treatment effect were revealed. Country-level measures may be helpful in the planning of future trials and in the translation of evidence into practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.15416","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T07:27:22Z","timestamp":1758526042000},"page":"3910-3919","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Geographic Region Variation in Patient Characteristics, Clinical Outcomes and Treatment of HFrEF in the VICTORIA Trial"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1082-5981","authenticated-orcid":false,"given":"Cynthia M.","family":"Westerhout","sequence":"first","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta , Edmonton, Alberta ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8549-7962","authenticated-orcid":false,"given":"Wendimagegn","family":"Alemayehu","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta , Edmonton, Alberta ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Cohen-Solal","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM UMR-S 942(MASCOT) , Paris ,","place":["France"]},{"name":"AP-HP Nord, Department of Cardiology, Lariboisiere University Hospital , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn S. P.","family":"Lam","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore and Duke-National University of Singapore \u00a0","place":["Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin A.","family":"Ezekowitz","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta , Edmonton, Alberta ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Corda","sequence":"additional","affiliation":[{"name":"Bayer AG , Basel ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciaran J.","family":"McMullan","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Inova Schar Heart and Vascular , Falls Church, Virginia ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0460-3445","authenticated-orcid":false,"given":"Paul W.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta , Edmonton, Alberta ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the VICTORIA Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"2026021804192543800_ehf215416-bib-0001","doi-asserted-by":"publisher","first-page":"3152","DOI":"10.1002\/ehf2.14468","article-title":"Pharmaco-disparities in heart failure: a survey of the affordability of guideline recommended therapy in 10 countries","volume":"10","author":"Averbuch","year":"2023","journal-title":"ESC Heart 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