Rationale and design of BROKEN-SWEDEHEART: a registry-based, randomized, parallel, open-label multicenter trial to test pharmacological treatments for broken heart (takotsubo) syndrome.


Journal

American heart journal
ISSN: 1097-6744
Titre abrégé: Am Heart J
Pays: United States
ID NLM: 0370465

Informations de publication

Date de publication:
03 2023
Historique:
received: 08 06 2022
revised: 07 11 2022
accepted: 10 11 2022
pubmed: 27 11 2022
medline: 15 2 2023
entrez: 26 11 2022
Statut: ppublish

Résumé

Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome without any evidence-based treatment options. No treatment for TS has been examined in a randomized trial. BROKEN-SWEDEHEART is a multicenter, randomized, open-label, registry-based 2 × 2 factorial clinical trial in patients with TS designed to test whether treatment with adenosine and dipyridamole accelerates cardiac recovery and improves clinical outcomes compared to standard care (study 1); and apixaban reduces the risk of thromboembolic events compared to no treatment with antithrombotic drugs (study 2). The trial will enroll 1,000 patients. Study 1 (adenosine hypothesis) will evaluate 2 coprimary end points: (1) wall motion score index at 48 to 96 hours (evaluated in the first 200 patients); and (2) the composite of death, cardiac arrest, need for mechanical assist device or heart failure hospitalization within 30 days or left ventricular ejection fraction <50% at 48 to 96 hours (evaluated in 1,000 patients). The primary end point in study 2 (apixaban hypothesis) is the composite of death or thromboembolic events within 30 days or the presence of intraventricular thrombus on echocardiography at 48 to 96 hours. BROKEN-SWEDEHEART will be the first prospective randomized multicenter trial in patients with TS. It is designed as 2 parallel studies to evaluate whether adenosine accelerates cardiac recovery and improves cardiac function in the acute phase and the efficacy of anticoagulation therapy for preventing thromboembolic complications in TS. If either of its component studies is successful, the trial will provide the first evidence-based treatment recommendation in TS. The trial has been approved by the Swedish Medicinal Product Agency and the Swedish Ethical Board and is registered at ClinicalTrials.gov (NCT04666454).

Sections du résumé

BACKGROUND
Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome without any evidence-based treatment options. No treatment for TS has been examined in a randomized trial.
STUDY DESIGN AND OBJECTIVES
BROKEN-SWEDEHEART is a multicenter, randomized, open-label, registry-based 2 × 2 factorial clinical trial in patients with TS designed to test whether treatment with adenosine and dipyridamole accelerates cardiac recovery and improves clinical outcomes compared to standard care (study 1); and apixaban reduces the risk of thromboembolic events compared to no treatment with antithrombotic drugs (study 2). The trial will enroll 1,000 patients. Study 1 (adenosine hypothesis) will evaluate 2 coprimary end points: (1) wall motion score index at 48 to 96 hours (evaluated in the first 200 patients); and (2) the composite of death, cardiac arrest, need for mechanical assist device or heart failure hospitalization within 30 days or left ventricular ejection fraction <50% at 48 to 96 hours (evaluated in 1,000 patients). The primary end point in study 2 (apixaban hypothesis) is the composite of death or thromboembolic events within 30 days or the presence of intraventricular thrombus on echocardiography at 48 to 96 hours.
CONCLUSIONS
BROKEN-SWEDEHEART will be the first prospective randomized multicenter trial in patients with TS. It is designed as 2 parallel studies to evaluate whether adenosine accelerates cardiac recovery and improves cardiac function in the acute phase and the efficacy of anticoagulation therapy for preventing thromboembolic complications in TS. If either of its component studies is successful, the trial will provide the first evidence-based treatment recommendation in TS.
CLINICAL TRIALS IDENTIFIER
The trial has been approved by the Swedish Medicinal Product Agency and the Swedish Ethical Board and is registered at ClinicalTrials.gov (NCT04666454).

Identifiants

pubmed: 36435233
pii: S0002-8703(22)00292-7
doi: 10.1016/j.ahj.2022.11.010
pii:
doi:

Substances chimiques

Adenosine K72T3FS567

Banques de données

ClinicalTrials.gov
['NCT04666454']

Types de publication

Randomized Controlled Trial Multicenter Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

33-40

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Elmir Omerovic (E)

Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: elmir@wlab.gu.se.

Stefan James (S)

Department of Cardiology, Uppsala University Hospital, Uppsala, Sweden.

David Erlinge (D)

Department of Cardiology, Lund University, Skåne University Hospital, Lund, Sweden.

Henrik Hagström (H)

Department of Cardiology, Umeå University Hospital, Umeå, Sweden.

Dimitrios Venetsanos (D)

Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

Loghman Henareh (L)

Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

Christina Ekenbäck (C)

Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.

Joakim Alfredsson (J)

Department of Cardiology, Linköping University Hospital, Linköping, Sweden.

Kristina Hambreus (K)

Department of Cardiology, Falun Hospital, Falun, Sweden.

Björn Redfors (B)

Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.

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Classifications MeSH