Canadian Amlodipine/Atenolol in Silent Ischemia Study - CASIS

Description:

Amlodipine vs. atenolol for ischemia suppression in stable angina.

Hypothesis:

Anti-ischemic drugs exert different effects on ischemia during ambulatory monitoring and ETT.

Study Design

Study Design:

Patients Screened: 194
Patients Enrolled: 100
Mean Follow Up: 6 weeks
Mean Patient Age: 60.8
Female: 18

Patient Populations:

At least one coronary artery stenosis (>70% lumen diameter reduction on coronary angiography.
A documented previous myocardial infarction (MI).
A previous radionuclide test reported as showing a reversible perfusion defect
Positive ETT (> 0.1 mV flat or downsloping ST segment depression measured 0.08 s after the J point.
48-h ambulatory recording includes 3 or more episodes of continuous ST segment depression (> 0.1 mV lasting for > 1 min, or > 10 min of total ST segment depression if there are only 1 or 2 episodes).

Exclusions:

Unstable symptoms within previous 3 months.
Cardiac surgery or stroke within the previous 6 months.
Congestive heart failure.
Hemodynamically significant valvular disease.
Sinus bradycardia < 60 bpm on a 12-lead ECG or any ECG abnormality that would preclude interpretation of the ST segment on ambulatory monitoring.

Primary Endpoints:

Ischemic episode frequency.

Secondary Endpoints:

Exercise time to angina.

Drug/Procedures Used:

Amlodipine, 5 to 10 mg/day; final dose for 2 weeks before treadmill testing and ambulatory monitoring.
Atenolol, 50 to 100 mg/day; final dose for 2 weeks before treadmill testing and ambulatory monitoring.
Combination of both; final dose quantity of first drug taken plus low dose of alternative agent, increased after 1 week if well tolerated. Final dose for 2 weeks before treadmill testing and ambulatory monitoring.

Concomitant Medications:

Not stated

Principal Findings:

Amlodipine and combination therapy prolonged exercise time to 0.1 mV ST segment depression by 29% and 35%, respectively (p < 0.001) versus 3% for atenolol (p = NS).

During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p=0.083 [NS]), by 57% with atenolol (p<0.002) and by 72% with the combination of both (p <0 .05 vs both single drugs); p < 0.001 vs. placebo).

Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina.

Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.05 vs. placebo and either single drug).

In those patients without angina, no therapy significantly improved total exercise time.

Interpretation:

Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination of both was more effective than either single drug in both settings.

References:

1. J Am Coll Cardiol 1995;25 619-25. Final results

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Interventions and Imaging, Angiography, Nuclear Imaging, Chronic Angina

Keywords: Monitoring, Ambulatory, Myocardial Infarction, Myocardial Ischemia, Coronary Stenosis, Angina, Stable, Coronary Angiography, Amlodipine, Calcium Channel Blockers, Exercise Test


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