Withdrawal of Pharmacological Treatment for Heart Failure Patients With Recovery From Tachycardia-induced Cardiomyopathy - WEAN-HF
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 348
- 试验地点
- 1
- 主要终点
- Patients free from heart failure deterioration 1 year after randomization
研究概览
简要总结
New onset heart failure (HF) is observed in up to 25% of patients with incident atrial fibrillation or flutter (AF). Current guidelines suggest that both conditions (AF & HF) be addressed with guideline directed medical therapy (GDMT) for HF and rate or rhythm control of AF. Hence, patients with both conditions are subjected to extensive polypharmacy with possible prognostic benefits, but also possible side effects, such as decreased renal function, dizziness, tiredness and hypotension, as well as the financial burden on both the individual patients and society, in addition to the stigma of having a HF diagnosis.
Guidelines do not inform how to manage long-term patients with HF, who following control of the incident tachycardia (e.g. AF), show full recovery from their HF condition.
This investigator-initiated, open-label, randomized, non-inferiority trial will test whether incremental weaning of GDMT in patients following full cardiac recovery and AF control is non-inferior compared to continuous GDMT with respect to the primary endpoint of freedom from heart failure deterioration. Furthermore, this study seeks to extensively phenotype these patients (genetic testing, advanced imaging, biomarkers etc.) in order to establish whether certain phenotypes are at lesser or greater risk of deterioration once remission is established. This novel approach of a personalized treatment regimen depending on e.g. genetic profiling could lead to an aggressive treatment in patients at high risk of deterioration and conversely spare patients with a negligible risk, a life-long intensive treatment regimen.
All HF clinics located in Zealand, Denmark, with a catchment area of >2 million citizens, have agreed to participate in the WEAN-HF trial. A total of 348 patients will be randomized. Patients are followed up the 1st year after randomization with clinical examination, biomarkers and echocardiography, and are subsequently followed via Danish nationwide registries for 10 years.
详细描述
Background:
Heart failure (HF) is a disease that affects more than 60000 patients in Denmark and millions across the world. The prognosis of HF is comparable to many types of cancer. New onset HF is observed in up to 25% of patients with incident atrial fibrillation or flutter (AF). The persistent tachycardia caused by AF is believed to exert the heart to a point where it causes HF. Whether AF is the cause of HF, or conversely that the detrimental effects of HF has induced AF, is difficult to ascertain upon the initial presentation. Current guidelines suggest that both conditions (AF & HF) be addressed with guideline directed medical therapy (GDMT) for HF and rate or rhythm control of AF. GDMT for HF consists of at least 4 different types of medication which is combined with management for AF (anticoagulant and often antiarrhythmic medication or ablation procedures). Hence, patients with both conditions are subjected to polypharmacy with at least 6 different types of medication in addition to their usual medication regimen. This may have prognostic benefits, but also possible side effects, such as decreased renal function, dizziness, tiredness and hypotension, as well as the financial burden on both the individual patients and society, in addition to the stigma of having a heart failure diagnosis.
Gaps in knowledge Data are lacking on how to optimally manage patients long-term with heart failure suspected to be tachycardia-induced, who following cessation or control of the incident AF, show full recovery from their heart failure condition. Guidelines do not suggest whether GDMT for heart failure should continue lifelong, cease or be weaned. In the TRED-HF study, 51 non-ischemic HF patients with LVEF recovery who were seemingly clinically stable were weaned from GDMT. Approximately 40% of patients showed signs of deterioration after 6 months of incremental GDMT weaning. Where TRED-HF patients had verified longstanding chronic HF, the situation for patients experiencing an incident episode of AF subsequently leading to acute heart failure may represent a different phenotype with a better prognosis once AF is terminated or controlled as suggested by observational data. Currently there is no data supporting how to manage GDMT in this population of heart failure patients with recovery following control of their AF episode.
Objective:
To observe whether incremental weaning of GDMT in patients following full cardiac recovery and AF control is non-inferior compared to continuous GDMT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with new onset heart failure (ambulatory or hospital) with reduced ejection fraction (LVEF≤40% assessed by echocardiography) and NYHA ≥2 and atrial fibrillation or atrial flutter with ventricular rate ≥110 bpm (ECG monitoring, hospital telemetry or Holter monitoring) that following GDMT - while AF is terminated (e.g. ablation or conversion) or controlled (HR<110 on resting ECG) - experience LVEF remission (LVEF ≥50%), normalization of indexed LV volume, and normal ECG (no bundle branch block, ST segment deviations or T-wave inversion) and NT-proBNP <250 pg/ml.
排除标准
- •18 years or older and able to consent
- •Former ablation procedures and inability to tolerate antiarrhythmic drugs
- •Pregnancy
- •Congenital heart disease (congenital defects with no hemodyamic effects are not excluded)
- •Previously genotyped positive for genes known to cause cardiomyopathy
- •Probable hypertrophic, restrictive or non-compaction cardiomyopathy
- •Moderate/severe valvular disease
- •Suspicion of or known cardiac amyloidosis, sarcoidosis, or other storage/inflammatory disease
- •More than 10% PVCs or documented sustained ventricular arrhythmias
- •History of persistent or permanent AF with ventricular rates >110 before incident HF despite best standard of care
- •eGFR < 30 ml/min/1.73 m2
- •Acute myocardial infarction at index
- •Probable medication-, alcohol- or illicit drug use induced AF and/or HF
- •Systolic blood pressure >160 mmHg (at multiple measurements) at index or history of uncontrollable hypertension
- •Myocarditis
- •Cardiogenic shock at index
- •Aborted sudden cardiac death
- •Pacing-induced cardiomyopathy
- •1.st degree relative with DCM
研究组 & 干预措施
Weaning
Patients will be weaned from GDMT in a sequential order.
干预措施: GDMT (Drug)
Standard of Care
Patients will be treated with GDMT for heart failure during the trial follow-up of 1 year.
结局指标
主要结局
Patients free from heart failure deterioration 1 year after randomization
时间窗: 1 year after randomization
Heart failure deterioration is defined as following; a reduction in LVEF of more than 10% and less than 50%, and/or increase in LVEDV by more than 10% and to higher than the normal range (indexed for body surface area), and/or hospitalization for heart failure and/or arrhythmia, and/or clinical evidence of heart failure.
次要结局
- Changes in Minnesota Living with Heart Failure Questionnaire from baseline(1 year after randomization)
- Changes in N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) from baseline(1 year after randomization)
- Patients needing changes in medication for AF (uptitration of current medication or change in/addition of new medication) or re-do ablation for AF(1 year after randomization)
- Non-CV hospitalizations(1 year after randomization + 10 year follow-up)
- CV death(1 year after randomization + 10 year follow-up)
- All-cause death(1 year after randomization + 10 year follow-up)
- Patients in need of initiation of loop diuretics or doubling of dosage(1 year after randomization)
- Patients with signs of AF that persistently exceed 110 bpm despite best practice(1 year after randomization)
- Cardiovascular (CV) hospitalizations(1 year after randomization)
- All-cause hospitalization(1 year after randomization)
研究者
Emil Wolsk
Head of Heart Failure, Principal investigator
Herlev and Gentofte Hospital