Effect of Heart Rate Control Using Ivabradine and Beta-blockers Combination Versus Beta-blockers Up-titration on Ventricular Pacing in Heart Failure Patients With an Implanted Cardioverter Defibrillator.
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Right ventricular pacing percentage increase > 50% or cardiovascular death or Heart failure decompensation or Crossover due to worsening heart failure.
研究概览
简要总结
The aim of this prospective, randomized and controlled trial is to evaluate the use of the ivabradine in combination to a low-dose of beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) to obtain heart rate (HR) control with reduction in RV pacing in single-chamber or dual chambers ICD recipients HF patients with moderate to severe left ventricular dysfunction (FE ≤ 40%) and an heart rate ≥ 70 bpm in sinus rhythm over a 12-months follow up.
Besides the investigators want to assess if the combination of ivabradine to a low-dose of beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) may determine a lower degree of left ventricular dysfunction progression, the reduction of ventricular arrhythmias burden and ICD appropriate therapy occurrence and the improvement of quality of life in ICD heart failure patients.
详细描述
Background
High heart rate (HR) represent per se a risk factor for cardiovascular mortality and heart failure (HF) progression, despite optimal HF therapy. Beta-blockers remain the therapy of choice in all patients with systolic HF, but they may worsen atrioventricular (AV) conduction and increase right ventricular (RV) pacing percentage. Several studies have demonstrated detrimental effects of RV pacing on cardiac function. Percent RV pacing > 40-50% is an independent predictor of death and hospitalization for HF in implantable cardioverter-defibrillator(ICD) patients, particularly in those with preexistent left ventricular dysfunction.1,2 Cumulative RV pacing > 2% and ejection fraction (EF) < 40% are independent predictors for Ventricular Tachycardia(VT)/Ventricular Fibrillation (VF) occurrence in ICD patients.3 Therefore reduction of cumulative RV pacing as far as possible should be achieved in ICD patients. Ivabradine is a specific inhibitor of the If current of the sinus node, that induces a selective and dose dependent HR reduction; it is a pure HR lowering agent without effects on AV conduction or contractility.4 In HF patients implanted with an ICD ivabradine could act as an heart rate control drug in combination with a beta-blocker without increase right ventricular (RV) pacing percentage and may be an option to reduce left-ventricular dysfunction progression and ventricular arrhythmias burden and appropriate ICD therapy.
Aim
The aim of this prospective, randomized and controlled trial is to evaluate the use of the ivabradine in combination to a low-dose of beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) to obtain heart rate (HR) control with reduction in RV pacing in single-chamber or dual chambers ICD recipients HF patients with moderate to severe left ventricular dysfunction (FE ≤ 40%) and an heart rate ≥70 bpm in sinus rhythm over a 12-months follow up.
Besides we want to assess if the combination of ivabradine to a low-dose of beta-blocker (bisoprolol) versus titration of beta-blocker (bisoprolol) may determine a lower degree of left ventricular dysfunction progression, the reduction of ventricular arrhythmias burden and ICD appropriate therapy occurrence and the improvement of quality of life in ICD heart failure patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Patients with stable chronic heart failure implanted with mono-cameral or bicameral ICD with a home monitoring remote control.
- •Moderate to severe left ventricular dysfunction (FE ≤ 40%).
- •Any cause of heart failure was allowed apart congenital heart disease.
- •Bicameral ICD programmed in DDD or AAI/DDD with AV interval < 300 msec.
- •Rest ECG heart rate ≥70 bpm;
- •Sinus rhythm.
- •In therapy with low-dose of beta-blocker (bisoprolol 1,25-2,5 mg) and with the maximum dose tolerated of angiotensin-converting enzyme inhibitor or blockade of angiotensin II receptor, mineralocorticoid antagonist, antiplatelet and lipid-lowering therapy, unless contraindicated.
排除标准
- •Inability of providing informed consent;
- •Age < 18 years.
- •State of pregnancy or lactation.
- •Recent (<2 months) myocardial infarction;
- •Contraindications to beta-blockers and ivabradine;
- •Rest ECG heart rate < 70 bpm;
- •No sinus rhythm.
- •Administration of non-dihydropyridinic calcium channels antagonists, digitalis, class I antiarrhythmic drugs, strong inhibitors of cytochrome P450 3A4 at the time of enrollment.
研究组 & 干预措施
ivabradine plus beta-blocker(bisoprolol)
Ivabradine will be administered at a dose of 5 mg twice daily in addition to a low dose of beta-blocker (bisoprolol 1,25 or 2,5 mg). After four weeks of treatment ivabradine will be eventually lowered up to 2,5 mg twice daily in the presence of side effects (phosphenes, diplopia, headache or dizziness).
干预措施: Ivabradine plus beta-blocker (bisoprolol) (Drug)
beta-blocker (bisoprolol) titration
Beta blocker Bisoprolol will be titrated biweekly starting from the initial dose of 1,25-2,5 mg daily up to the max dose of 10 mg daily or to the maximum tolerated dose.
干预措施: betablocker titration (Drug)
结局指标
主要结局
Right ventricular pacing percentage increase > 50% or cardiovascular death or Heart failure decompensation or Crossover due to worsening heart failure.
时间窗: 12 months
次要结局
- Composite endpoint: number of cardiovascular death and hospitalization due to worsening heart failure.(12 months)
- Number of episodes of non-sustained and sustained ventricular tachycardia and ventricular fibrillation(12 months)
- Ejection fraction decrease < 5% from baseline value(12 months)
- Left Ventricular End-Systolic Volume decrease <15% from baseline value(12 months)
- Heart rate variability increase (> 10%) from baseline value(12 months)
- reduction of at least one NYHA Class from baseline value(12 months)
- Change in Minnesota Living Heart Failure Questionnaire scores (>5) from the baseline score.(12 months)
- Right ventricular pacing percentage reduction (> 10%) from baseline value(12 months)
- Number of ICD shock-delivery for ventricular fibrillation and sustained ventricular tachycardia(12 months)
- Crossover rate due to worsening heart failure(12 months)
研究者
Leonardo Calò, MD
MD, FESC
Policlinico Casilino ASL RMB