Impact of Geographic Region on the COMMANDER-HF Trial.


Journal

JACC. Heart failure
ISSN: 2213-1787
Titre abrégé: JACC Heart Fail
Pays: United States
ID NLM: 101598241

Informations de publication

Date de publication:
03 2021
Historique:
received: 21 10 2020
revised: 12 11 2020
accepted: 16 11 2020
pubmed: 8 2 2021
medline: 26 10 2021
entrez: 7 2 2021
Statut: ppublish

Résumé

This study sought to compare patient characteristics, outcomes, and treatment effects among regions in the COMMANDER-HF trial. Globalization of cardiovascular trials increases generalizability. However, regional differences may also introduce heterogeneity in results. Incidence rates and interactions with treatment were recorded in pre-specified regions: Eastern Europe, Western Europe and South Africa, North America, Asia-Pacific, and Latin America. Most patients (n = 3,224; 64.2%) were from Eastern Europe; 458 (9.1%) were from Western Europe and South Africa; 149 (3.0%) were from North America; 733 (14.6%) were from Asia-Pacific; and 458 (9.1%) were from Latin America. Compared with patients from Eastern Europe, patients from Western Europe and South Africa, North America, and Asia-Pacific were older and more likely to have coronary interventions and cardiac devices. Patients from Eastern Europe had the lowest event rates. For the primary outcome of myocardial infarction (MI), stroke, or all-cause death, event rates (100/year) were 11.6 in Eastern Europe (10.8 to 12.5); 19.5 (16.5 to 23.0) in Western Europe and South Africa; 14.2 (10.5 to 19.2) in North America; 17.7 (15.4 to 20.3) in Asia-Pacific; and 18.6 (15.6 to 22.1) in Latin America. There was a lower incidence of bleeding in Eastern Europe. Blood concentrations of rivaroxaban (Xarelto, Titusville, New Jersey) at 4 weeks were undetectable in 21% patients from Eastern Europe (n = 128) compared to 5% in other regions (n = 42). There was no evidence of treatment-by-region heterogeneity for the primary outcome (interaction In the COMMANDER-HF study, patients from Eastern Europe had a lower risk profile and fewer cardiovascular and bleeding events, possibly related to lower treatment adherence. Those differences might have influenced the effect of rivaroxaban therapy. (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure [COMMANDER HF]; NCT01877915).

Sections du résumé

OBJECTIVES
This study sought to compare patient characteristics, outcomes, and treatment effects among regions in the COMMANDER-HF trial.
BACKGROUND
Globalization of cardiovascular trials increases generalizability. However, regional differences may also introduce heterogeneity in results.
METHODS
Incidence rates and interactions with treatment were recorded in pre-specified regions: Eastern Europe, Western Europe and South Africa, North America, Asia-Pacific, and Latin America.
RESULTS
Most patients (n = 3,224; 64.2%) were from Eastern Europe; 458 (9.1%) were from Western Europe and South Africa; 149 (3.0%) were from North America; 733 (14.6%) were from Asia-Pacific; and 458 (9.1%) were from Latin America. Compared with patients from Eastern Europe, patients from Western Europe and South Africa, North America, and Asia-Pacific were older and more likely to have coronary interventions and cardiac devices. Patients from Eastern Europe had the lowest event rates. For the primary outcome of myocardial infarction (MI), stroke, or all-cause death, event rates (100/year) were 11.6 in Eastern Europe (10.8 to 12.5); 19.5 (16.5 to 23.0) in Western Europe and South Africa; 14.2 (10.5 to 19.2) in North America; 17.7 (15.4 to 20.3) in Asia-Pacific; and 18.6 (15.6 to 22.1) in Latin America. There was a lower incidence of bleeding in Eastern Europe. Blood concentrations of rivaroxaban (Xarelto, Titusville, New Jersey) at 4 weeks were undetectable in 21% patients from Eastern Europe (n = 128) compared to 5% in other regions (n = 42). There was no evidence of treatment-by-region heterogeneity for the primary outcome (interaction
CONCLUSIONS
In the COMMANDER-HF study, patients from Eastern Europe had a lower risk profile and fewer cardiovascular and bleeding events, possibly related to lower treatment adherence. Those differences might have influenced the effect of rivaroxaban therapy. (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure [COMMANDER HF]; NCT01877915).

Identifiants

pubmed: 33549557
pii: S2213-1779(20)30702-2
doi: 10.1016/j.jchf.2020.11.007
pii:
doi:

Substances chimiques

Rivaroxaban 9NDF7JZ4M3

Banques de données

ClinicalTrials.gov
['NCT01877915']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

201-211

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures The COMMANDER-HF trial was supported by Janssen Research and Development. Drs. Ferreira, Rossignol, and Zannad are supported by Reseau Hospitalo-Universitaire Fight-HF, a public grant overseen by the French National Research Agency as part of the second “Investissements d’Avenir” program (reference: ANR-15-RHUS-0004) and by the French Investments for the Future Program project “Lorraine Université d’Excellence” (reference: ANR-15-IDEX-04-LUE). The biobanking for rivaroxaban dosages is managed by Biological Resource Center Lorrain BB-0033-00035. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Auteurs

João Pedro Ferreira (JP)

Centre d'Investigations Cliniques Plurithématique, Université de Lorraine, Inserm 1433, Nancy, France, Centre Hospitalier Régional Universitaire (CHRU) de Nancy, Inserm U1116, Nancy, France, French Clinical Research Infrastructure Network Investigation Network Initiative - Cardiovascular and Renal Clinical Trialists, Nancy, France. Electronic address: j.ferreira@chru-nancy.fr.

John G F Cleland (JGF)

Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, Scotland.

Carolyn S P Lam (CSP)

National Heart Centre Singapore, Duke-National University of Singapore, Singapore; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Dirk J van Veldhuisen (DJ)

Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

William M Byra (WM)

Janssen Research and Development, Raritan, New Jersey, USA.

David A La Police (DA)

Janssen Research and Development, Raritan, New Jersey, USA.

Stefan D Anker (SD)

Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany; Department of Cardiology, German Center for Cardiovascular Research, partner site Berlin, Charite Universitatsmedizin Berlin, Berlin, Germany.

Mandeep R Mehra (MR)

Heart and Vascular Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Céline Leroy (C)

Centre d'Investigations Cliniques Plurithématique, Université de Lorraine, Inserm 1433, Nancy, France, Centre Hospitalier Régional Universitaire (CHRU) de Nancy, Inserm U1116, Nancy, France, French Clinical Research Infrastructure Network Investigation Network Initiative - Cardiovascular and Renal Clinical Trialists, Nancy, France.

Valerie Eschwege (V)

Laboratoire d'Hématologie Biologique, CHRU de Nancy, Nancy, France.

Marie Toussaint-Hacquard (M)

Laboratoire d'Hématologie Biologique, CHRU de Nancy, Nancy, France.

Patrick Rossignol (P)

Centre d'Investigations Cliniques Plurithématique, Université de Lorraine, Inserm 1433, Nancy, France, Centre Hospitalier Régional Universitaire (CHRU) de Nancy, Inserm U1116, Nancy, France, French Clinical Research Infrastructure Network Investigation Network Initiative - Cardiovascular and Renal Clinical Trialists, Nancy, France.

Barry Greenberg (B)

Cardiology Division, Department of Medicine, University of California San Diego, La Jolla, California, USA.

Faiez Zannad (F)

Centre d'Investigations Cliniques Plurithématique, Université de Lorraine, Inserm 1433, Nancy, France, Centre Hospitalier Régional Universitaire (CHRU) de Nancy, Inserm U1116, Nancy, France, French Clinical Research Infrastructure Network Investigation Network Initiative - Cardiovascular and Renal Clinical Trialists, Nancy, France.

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Classifications MeSH