Effects of Ivabradine on Residual Myocardial Ischemia After PCI

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

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.

Study Overview

• Status: Completed
• Conditions: Angina Pectoris, Stable
• Intervention / Treatment: Drug: Ivabradine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00100
    • Massimo Mancone

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control Group; drug therapy according to the guidelines
EXPERIMENTAL: Ivabradine Group; drug therapy according to the guidelines + Ivabradine 5 mg twice a day	Drug: Ivabradine; Ivabradine 5 mg twice a day; Other Names: Procoralan; Corlentor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Azienda Policlinico Umberto I
• Investigators: Principal Investigator: Massimo Mancone, Department of Cardiovascular disease, Sapienza, University of Rome, Italy

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 5, 2015
• Primary Completion (ACTUAL): March 7, 2017
• Study Completion (ACTUAL): March 7, 2017

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (ACTUAL): March 7, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 7, 2019
• Last Update Submitted That Met QC Criteria: March 5, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: diastolic function; Stable angina; ivabradine; heart rate; coronary artery diseases; exercise tolerability
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Coronary Disease; Chest Pain; Coronary Artery Disease; Myocardial Ischemia; Ischemia; Angina Pectoris; Angina, Stable
• Other Study ID Numbers: 04091990

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No