Informations générales (source: ClinicalTrials.gov)
Beta-blOckers discoNtinuation in Patients Presenting Heart FaIlure With REcovered Left Ventricular Ejection Fraction
Interventional
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
octobre 2024
octobre 2027
28 août 2025
A significant proportion of patients initially diagnosed with heart failure and a reduced
left ventricular ejection fraction (LVEF<40%, HFrEF) presents a substantial improvement
in response to evidence-based medical and device therapies. Some of these patients
(estimated from 20 to 30%) even display a complete normalization of LVEF (i.e., >50%) and
are now recognized as a specific sub-group of patients named Heart Failure with recovered
Ejection Fraction (HFrecovEF). Different studies have shown that reverse remodeling with
recovery of cardiac function and stabilization of HF symptoms are associated with
improved clinical outcomes over the long-term. Whether these patients present a stable
remission of HF and could benefit a therapeutic de-escalation is however unclear. Until
novel data are provided, medical therapies are thus continued indefinitely in these
stable patients with HFrecovEF. Current guidelines for the management of patients with
heart failure and a reduced left ventricular ejection fraction recommends a comprehensive
therapy, including 5 different therapeutic classes (RAAS blockers (with a preference for
ARNi) + Beta-Blockers + SGLT2i + Mineraloreceptors Antagonists + or - Diuretics ).
None of these therapies (with the recent exception of one SGLT2i, i.e. Dapagliflozin)
have been tested in patients with HFrecovEF. In addition, it is unclear whether the
benefit of older therapies (notably beta-blockers) remains in patients receiving modern
comprehensive therapy as newer drugs were tested as add-on therapies. This polypharmacy
is lowering adherence and is creating a challenge for physicians and patients.
Betablockers are notably associated with frequent side effects, a limited tolerance and a
significant reduction of quality of life. Their efficacy on outcomes is not established
in patients with normal LVEF. Pilot studies have suggested that Beta-blockers
interruption in patients with HF and normal EF was associated with functional
improvement.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CENTRE CARDIOLOGIQUE DU NORD | HULOT Jean-sebastien | 01/11/2025 08:01:18 | Contacter | ||
| CH DE VERSAILLES SITE ANDRE MIGNOT | HULOT Jean-sebastien | 01/11/2025 08:01:17 | Contacter | ||
| GH PARIS SITE SAINT JOSEPH | HULOT Jean-sebastien | 01/11/2025 08:01:17 | Contacter | ||
| HOPITAL NOVO | HULOT Jean-sebastien | 01/11/2025 08:01:18 | Contacter | ||
| AP-HP Assistance publique - Hôpitaux de Paris | 01/11/2025 08:01:19 | Contacter | |||
| AP-HP - Hôpital Bicêtre | |||||
| AP-HP - Hôpital Bichat | |||||
| AP-HP - Hôpital Broca-La Rochefoucauld-La Collégiale | |||||
| AP-HP - Hôpital Europeen Georges Pompidou | |||||
| AP-HP - Hôpital La Pitié-Salpêtrière | |||||
| AP-HP - Hôpital Lariboisiere-Fernand Widal | |||||
| AP-HP - Hôpital Saint Antoine | |||||
Critères
Tous
Inclusion Criteria:
1. Age ≥ 18 years-old
2. Established diagnosis of HF for more than 12 months, from an ischemic or a
non-ischemic origin
3. With a documented history of reduced left ventricular ejection fraction (LVEF ≤
45%), followed by a normalisation of LVEF (≥ 50 % for the last 6 months) assessed by
cardiac echography.
4. With a left ventricular end diastolic volume indexed to body surface area (LVEDVi)
within the normal range (≤74ml/m2 in men and ≤61 ml/m2 in women)
5. No or mild symptoms of HF (defined as NYHA functional class I or II)
6. No heart failure-related hospital admission within the last six months
7. Currently receiving a beta-blocker indicated for chronic heart failure (i.e.
bisoprolol or carvedilol or metoprolol or nebivolol) whatever the dose used, for at
least 12 months
8. And receiving the guideline-directed optimal medical therapy for at least 12 months
(i.e., maximal tolerated dose of SGLT2 inhibitors, and of RAAS blocker (Angiotensin
receptor neprilysin inhibitor OR Angiotensin-converting-enzyme-inhibitors OR
Angiotensin II receptors blockers), and MRA if tolerated). Loop diuretics use is
adjusted to congestive signs according to physicians' decision.
9. With or without ICD
10. Ability to provide written informed consent to participate to the study
11. Patient affiliated to Social Security
1. Age ≥ 18 years-old
2. Established diagnosis of HF for more than 12 months, from an ischemic or a
non-ischemic origin
3. With a documented history of reduced left ventricular ejection fraction (LVEF ≤
45%), followed by a normalisation of LVEF (≥ 50 % for the last 6 months) assessed by
cardiac echography.
4. With a left ventricular end diastolic volume indexed to body surface area (LVEDVi)
within the normal range (≤74ml/m2 in men and ≤61 ml/m2 in women)
5. No or mild symptoms of HF (defined as NYHA functional class I or II)
6. No heart failure-related hospital admission within the last six months
7. Currently receiving a beta-blocker indicated for chronic heart failure (i.e.
bisoprolol or carvedilol or metoprolol or nebivolol) whatever the dose used, for at
least 12 months
8. And receiving the guideline-directed optimal medical therapy for at least 12 months
(i.e., maximal tolerated dose of SGLT2 inhibitors, and of RAAS blocker (Angiotensin
receptor neprilysin inhibitor OR Angiotensin-converting-enzyme-inhibitors OR
Angiotensin II receptors blockers), and MRA if tolerated). Loop diuretics use is
adjusted to congestive signs according to physicians' decision.
9. With or without ICD
10. Ability to provide written informed consent to participate to the study
11. Patient affiliated to Social Security
1. Atrial, supra-ventricular, or ventricular arrhythmias, in the last 12 months and/or
requiring beta-blockers according to investigator.
2. Uncontrolled arterial hypertension according to investigator decision.
3. Symptomatic angina or evidence of infra-clinic myocardial ischemia requiring
beta-blockers according to investigator decision.
4. Cardiac resynchronization therapy
5. Extra-cardiac conditions requiring beta-blockers (migraine, essential tremor,
prevention of bleeding from esophageal varices in patients with liver cirrhosis,
adrenergic symptoms of hyperthyroidism...) according to investigator decision.
6. History of severe outcomes at beta-blockers interruption: HF relapse, occurrence of
arrythmias
7. Severe valvulopathy, restrictive, infiltrative or hypertrophic cardiomyopathy,
constrictive pericarditis, or acute myocarditis within 3 months prior to inclusion
Visit.
8. Planned coronary, carotid, or peripheral artery revascularization known at the day
of inclusion
9. Chronic renal failure with eGFR <20mL/Min per 1.73m² (CKD-Epi) at inclusion
10. Hepatic insufficiency classified as Child-Pugh B or C at the inclusion Visit.
11. Any past solid organ transplantation or planned organ transplantation within 12
months
12. Any condition other than HF that could limit survival to less than one year
13. Pregnancy or breastfeeding women or women of childbearing potential without adequate
contraceptive method
14. Current participation in another interventional trial.
15. Patient under legal protection (protection of the court, or in curatorship or
guardianship).
16. Any disorder, unwillingness or inability, which in investigator's opinion, might
jeopardise the patient's safety or compliance with the protocol