Heart Rate Reduction in Heart Failure

Study Overview
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Brief Summary
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Patients with heart failure (HF) have a limited exercise tolerance,few pharmacological interventions have been proven effective in improving exercise capacity. At the presence there i conflicting evidence on the effectiveness of beta-blockers on exercise capacity. Ivabradine has been shown to improve prognosis in patients with ischemic heart disease, left ventricular dysfunction and heart rate > 70 bpm. The association of ivabradine and atenolol has been proven effective in increasing exercise tolerance in patients with ischemic heart disease. Aim of the present study is to evaluate the effect of heart rate reduction with ivabradine, carvedilol or their combination in patients with heart failure of ischemic origin.

Detailed Description
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Patients with chronic heart failure of ischemic origin (120) Stable coronary artery disease Acute coronary syndromes > 3 months Revascularization procedures > 3 months Naive on heart rate reducing agents New York Heart Association (NYHA) Class II III 6 minute walking test (6MW) tolerance between 200 and 400 m Stable medications for the past 3 months Treatment Ivabradine up to 7.5 mg b.i.d. Carvedilol up to 25 mg b.i.d. Carvedilol and Ivabradine up to 12.5/5 mg b.i.d. Efficacy measure Intention to treat Exercise tolerance Quality of life

Official Title
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Effect of Ivabradine, Carvedilol or Their Combination in Patients With Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: ivabradine
* Drug: Drug:Carvedilol and Drug:Ivabradine
* Drug: Carvedilol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: heart failure II-III ischemic origin stable medications from at least 3 months > 3 months from an acute ischemic syndrome or revascularization procedure naive on heart rate reducing agents Exclusion Criteria: bradycardia hypersensitivity or contraindications to study drugs exercise tolerance at 6 minute walking test <100 m or >400 m

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ivabradine<br>7.5 mg bd | Drug: ivabradine<br>* 7.5 mg bd<br>|
| Active Comparator: Carvedilol<br>up to 25 mg bd | Drug: Carvedilol<br>* 25 mg bd<br>|
| Experimental: Drug:Carvedilol and Drug:Ivabradine<br>up to 12.5/5 mg bd | Drug: Drug:Carvedilol and Drug:Ivabradine<br>* up to 12.5/5 mg bd<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise Tolerance Assessed by 6 Minute Walking Test | Distance measured at 6 minute walking test. The 6 minute walking test was performed according to standardised procedure at baseline, before inclusion (at least 1 week after baseline evaluation), and at the end of the study. Patients who had not done at least two tests in the past underwent two practice 6 minute walking tests at least 3 days apart. Results are expressed in terms of distance walked (metres). The test was supervised by a physical therapist. Patients were asked to walk at their own maximal pace a 100 m long hospital corridor. At the beginning of the last (6th) minute of the test a standard phrase of encouragement was told. Patients were allowed to stop if signs or symptoms of significant distress occurred (dyspnea, angina), through they were instructed to resume walking as soon as possible. | 3 months | 
| Maximal Oxygen Consumption | Functional capacity was assessed by means of a cardiopulmonary exercise test with a bicycle ergometer with gas exchange monitoring (Vmax 29 C, SensorMedics). Peak oxygen consumption was defined as the maximal oxygen consumption (MVO2) observed during exercise. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | Quality of life (QoL) was evaluated using the Visual Analogue Scale (VAS) which is a global measurement of QoL, allowing a subjective assessment of the impact of the disease and treatment. Patients are asked to indicate their current state in a line from 0 (worst state) to 10 (best state), with higher values therefore representing a better outcome. | 3 months | 
| New York Heart Association (NYHA) Class | The 1994 NYHA Classification system is a measure of functional status. It was designed for clinical assessment of patients by physicians as NYHA class I, II, III, or IV, on the basis of patient's limitations in physical activities caused by cardiac symptoms. Class I describes patients with cardiovascular disease (CVD) but without resulting limitation of physical activity. There is no objective evidence of CVD. Class II describes patients with CVD resulting in slight limitation of physical activity. There is objective evidence of minimal CVD. Class III describes patients with CVD resulting in marked limitation of physical activity. There is objective evidence of moderately severe CVD. Class IV describes patients with CVD resulting in inability to carry on any physical activity without discomfort. There is objective evidence of severe CVD. Here we report data on number of patients showing an improvement by at least one NYHA class according to treatment allocation. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart failure, heart rate, ivabradine, carvedilol