A Comparative Study to Assess the Efficacy of Nicorandil+Atenolol vs Atenolol in Treatment naïve Patients of Chronic Stable Angina.
Trial Snapshot
- Phase
- Phase 4
- Sponsor
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- SPECT Tc99m- Tetrofosmin (MYOVIEW)
Study Overview
Brief Summary
This study is to determine the anti-anginal and anti-ischemic effect of k-channel opener, nicorandil in patients of chronic stable angina.
Detailed Description
Stress myocardial perfusion imaging (MPI) is widely used for the diagnosis and risk assessment of patients with known or suspected coronary artery disease (CAD). Also, MPI lends itself to monitoring the effects of therapeutic interventions such as anti-ischemic medications, gene therapy, and various percutaneous and surgical revascularization modalities.
The effects of nitrates, potassium channel activators, calcium-channel blockers, and beta-blockers on myocardial perfusion imaging are likely attributable to changes in myocardial blood flow and myocardial oxygen supply-demand ratio. The major anti-ischemic effect of BBs is a reduction in myocardial oxygen consumption both at rest and during stress. Beta-blockers decrease myocardial oxygen demand through a reduction in heart rate, blood pressure, and myocardial contractility. They also prolong diastole, therefore increasing coronary perfusion time. The effect of chronic atenolol use on dipyridamole SPECT MPI was assessed in a randomized, double-blind, crossover study that showed no difference in the perfusion defect size and severity between placebo and atenolol for the group as a whole, although one-third of patients had larger defects on atenolol than placebo. Bridges et al., 1992 (56)
Nicorandil, a potassium channel activator, when given for 3 weeks exhibited significant improvement in myocardial perfusion in both MI and angina patients, on exercise thallium scan. Yamazaki et al., 1993 (69).
Atenolol as shown in the cross over study does not affect myocardial perfusion significantly and hence combination therapy with nicorandil will help us to determine a significant benefit of nicorandil on MP. Results will be analyzed from base line in the same arm and the difference will be further compared with control arm.
Guidelines suggest beta blockers as first line of therapy. To assess the anti ischemic effects of nicorandil, combination therapy with atenolol will be compared with atenolol alone. Since atenolol effect on MP is insignificant an added advantage of nicorandil can be evaluated in comparative study.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 25 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients of chronic stable angina with abnormal Exercise Myocardial Perfusion Spect Scan with reversible and partially reversible ischemic changes.
- •Male and female
- •Age 25 to 65 years
- •Patient must understand and be willing, able and likely to comply with all study procedures and restrictions and comprehends the diary cards.
- •Patient must be able to give voluntary written informed consent.
Exclusion Criteria
- •Hypertension of > 170/100 mm of Hg
- •Valvular heart disease and cardiomyopathy
- •Myocardial infarction in < 6 months
- •Unstable angina
- •Congestive cardiac failure
- •Severe anemia (Hb 7G/dl)
- •Cardiac arrhythmias or II or III degree AV block
- •Significant liver or renal dysfunction
- •IDDM (Type-1 diabetes mellitus)
- •Systolic blood pressure < 100 mm Hg
- •Pregnant and nursing women
- •Known hypersensitivity to nicorandil
- •On calcium channel blockers
- •Patients not eligible for Tc 99m SPECT
- •Patients in whom beta blockers are contraindicated
- •Geographical inaccessibility for treatment or follow-up evaluations
Arms & Interventions
Nicorandil test arm
Nicorandil is given with atenolol therapy.
Intervention: Nicorandil (Drug)
Atenolol control arm
Atenolol 50 mg OD is given.
Intervention: Atenolol (Drug)
Outcomes
Primary Outcomes
SPECT Tc99m- Tetrofosmin (MYOVIEW)
Time Frame: 4 weeks
Changes in perfusion will be evaluated in each arm at week 4 and comparison between the two study arms will be made to document the anti ischemic effects of nicorandilusing Ex- SPECT MPI. * Improvement in SDS after 4 weeks of treatment (Summed Stress Score SSS, Summed Rest Score SRS, Summed Difference Score SDS) * Difference in number of reversible, partially reversible defects. * Improvement in the extent and severity of ischemic lesions.
Secondary Outcomes
- Exercise ECG Testing - Bruce protocol(4weeks)
Investigators
Dr. Tariq Ashraf
Assistant Professor Of cardiology, National Institute of Cardiovascular Diseases
Ferozsons Laboratories Ltd.