Effects of Ivabradine on Residual Myocardial Ischemia After PCI

Study Overview
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Brief Summary
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This is a randomized pharmacological study evaluating the effects of ivabradine in patients with residual angina after PCI. The role of ivabradine in patients with angina, without systolic dysfunction, is not yet clear. The investigators performed in all patients an echostress to evaluate the effects of therapy with ivabradine after 30 days in terms of exercise tolerance and diastolic function.

Detailed Description
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BACKGROUND. Residual angina after PCI is a frequently-occurring disease. Ivabradine improves symptoms but its role in patients without left-ventricular systolic dysfunction is still unclear. The aim was to quantify the effects of ivabradine in terms of MVO2 indicators and diastolic function. METHODS. 28 consecutive patients with residual angina after PCI were randomized to ivabradine 5 mg twice/day(IG) or standard therapy(CG). All patients performed a stress echocardiography at the enrollment and after 30 days. Myocardial oxygen consumption was estimated from: double product(DP); triple product(TP) integrating DP with ejection-time(ET). Diastolic function was evaluated determining E and A waves, E' measurements and E/E' ratio both at rest and at the peak of exercise.

Official Title
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Effects of Ivabradine on Residual Myocardial Ischemia After PCI Evaluated by Stress Echocardiography

Conditions
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Angina Pectoris, Stable

Intervention / Treatment
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* Drug: Ivabradine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: coronary artery disease with chronic stable angina for more than three months (Canadian Cardiovascular Society-CCS-class I-III); percutaneous revascularization with stent implantation at least one; signs/symptoms of residual ischemia; sinus rhythm; HR ≥ 70 bpm at rest; ability to perform an echocardiogram stress test with the tilting bicycle stress test (BST); good acoustic window; age ≥ 18 years. Exclusion Criteria: drugs intolerance or hypersensitivity EF ≤ 40 % NYHA class III to IV; CCS IV atrial fibrillation or flutter presence of a pacemaker or implantable defibrillator II or III degree AV block HR ≤ 70 bpm at rest or sick sinus syndrome any condition that could interfere with the ability to exercise stress test like Wolff- Parkinson-White syndrome, left bundle branch block, left ventricular hypertrophy; rate-corrected QT interval (QTc) greater than 500 ms or the use of drugs that prolong the QTc interval symptomatic hypotension or uncontrolled hypertension (systolic blood pressure at rest ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg) severe liver disease and severe renal impairment (creatinine clearance ≤ 30 ml/min) electrolyte disorders uncontrolled thyroid disease pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Group<br>drug therapy according to the guidelines | |
| Experimental: Ivabradine Group<br>drug therapy according to the guidelines + Ivabradine 5 mg twice a day | Drug: Ivabradine<br>* Ivabradine 5 mg twice a day<br>* Other names: Corlentor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Double product (DP) calculated as a product between HR and systolic blood pressure. (unit of measure: beats per minute x mmHg) | These, indirectly, reflect the true myocardial oxygen consumption (MVO2) and the improvement of mechanical load that the ventricle can withstand at different levels of exercise. | 30 days | 
| Triple product (TP), calculated as a product between HR, systolic blood pressure and ejection time. (unit of measure: beats per minute x mmHg x msec) | These, indirectly, reflect the true myocardial oxygen consumption (MVO2) and the improvement of mechanical load that the ventricle can withstand at different levels of exercise. | 30 days | 
| chronotropic reserve (unit of measure: beats per minute) | difference between resting heart rate and maximum heart rate at peak exercise | 30 days | 
| muscular work (unit of measure: watt) | These, indirectly, reflect the myocardial oxygen consumption (MVO2) and the improvement of mechanical load that the ventricle can withstand at different levels of exercise. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| diastolic function: PW Doppler E wave (unit of measure: cm/sec) | ventricular filling echocardiographic parameter | 30 days | 
| diastolic function: TDI derived E' measurements (unit of measure: cm/sec) | ventricular filling echocardiographic parameter. Mitral annular E' velocity was estimated as the average between lateral and septal velocity. | 30 days | 
| diastolic function: PW Doppler A wave (unit of measure: cm/sec) | ventricular filling echocardiographic parameter | 30 days | 
| E/E' ratio | ventricular filling echocardiographic parameter. TDI derived E' measurements (unit of measure: cm/sec). PW Doppler E wave (unit of measure: cm/sec) | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stable angina, coronary artery diseases, heart rate, exercise tolerability, diastolic function, ivabradine