Heart Failure
Conditions
Keywords
heart failure, heart rate, ivabradine, carvedilol
Brief summary
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
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
Interventions
7.5 mg bd
up to 12.5/5 mg bd
25 mg bd
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exercise Tolerance Assessed by 6 Minute Walking Test | 3 months | 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. |
| Maximal Oxygen Consumption | 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life | 3 months | 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. |
| New York Heart Association (NYHA) Class | 3 months | 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. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ivabradine up to 7.5 mg b.i.d. | 41 |
| Carvedilol up to 25 mg b.i.d. | 38 |
| Carvedilol and Ivabradine up to 12.5 / 5 mg b.i.d. | 42 |
| Total | 121 |
Baseline characteristics
| Characteristic | Ivabradine | Carvedilol | Carvedilol and Ivabradine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 9 Participants | 10 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 29 Participants | 32 Participants | 91 Participants |
| Exercise Tolerance Assessed by 6 Minute Walking Test | 346.7 meters STANDARD_DEVIATION 112 | 379.0 meters STANDARD_DEVIATION 96.3 | 358.2 meters STANDARD_DEVIATION 107.6 | 361.3 meters STANDARD_DEVIATION 105.3 |
| Maximal Oxygen Consumption | 12.05 mL/Kg/min STANDARD_DEVIATION 2.1 | 12.3 mL/Kg/min STANDARD_DEVIATION 2.6 | 12.4 mL/Kg/min STANDARD_DEVIATION 2.5 | 12.25 mL/Kg/min STANDARD_DEVIATION 2.4 |
| New York Heart Association (NYHA) class class II | 20 participants | 22 participants | 21 participants | 63 participants |
| New York Heart Association (NYHA) class class III | 21 participants | 16 participants | 21 participants | 58 participants |
| Quality of Life | 4.3 units on a scale STANDARD_DEVIATION 0.5 | 4.6 units on a scale STANDARD_DEVIATION 0.8 | 4.7 units on a scale STANDARD_DEVIATION 0.8 | 4.5 units on a scale STANDARD_DEVIATION 0.7 |
| Region of Enrollment Italy | 41 participants | 38 participants | 42 participants | 121 participants |
| Sex/Gender, Customized FEMALE | 13 participants | 12 participants | 14 participants | 39 participants |
| Sex/Gender, Customized MALE | 28 participants | 26 participants | 28 participants | 82 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 41 | 0 / 38 | 0 / 42 |
| serious Total, serious adverse events | 0 / 41 | 0 / 38 | 0 / 42 |
Outcome results
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ivabradine | Exercise Tolerance Assessed by 6 Minute Walking Test | 474.8 meters | Standard Deviation 127.3 |
| Carvedilol | Exercise Tolerance Assessed by 6 Minute Walking Test | 435.7 meters | Standard Deviation 121.3 |
| Carvedilol and Ivabradine | Exercise Tolerance Assessed by 6 Minute Walking Test | 453.1 meters | Standard Deviation 87.4 |
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ivabradine | Maximal Oxygen Consumption | 15.8 mL/Kg/min | Standard Deviation 1.9 |
| Carvedilol | Maximal Oxygen Consumption | 12.9 mL/Kg/min | Standard Deviation 2.4 |
| Carvedilol and Ivabradine | Maximal Oxygen Consumption | 14.7 mL/Kg/min | Standard Deviation 1.6 |
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.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ivabradine | New York Heart Association (NYHA) Class | 30 participants |
| Carvedilol | New York Heart Association (NYHA) Class | 5 participants |
| Carvedilol and Ivabradine | New York Heart Association (NYHA) Class | 20 participants |
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ivabradine | Quality of Life | 6.7 units on a scale | Standard Deviation 0.9 |
| Carvedilol | Quality of Life | 4.1 units on a scale | Standard Deviation 0.6 |
| Carvedilol and Ivabradine | Quality of Life | 6.1 units on a scale | Standard Deviation 0.6 |