Study Design

Study Design:

Patients Enrolled: 356
Mean Follow Up: Five weeks
Mean Patient Age: 18 to 75
Female: 15

Patient Populations:

Men and women ages 18-75 with typical angina complaints. All patients had to be treated with metoprolol controlled release 100 or 200 mg daily for at least four weeks prior to entering the study. The response to beta blockade had to be adequate (hazard ratio <65) and no contraindications to beta blockade could be present. Myocardial ischemia despite beta blockade had to be confirmed with exercise testing with at least 1 mm horizontal or downsloping change of ST segments (80 ms after J point) within 80% of the maximal predicted workload.

Exclusions:

A difference in total exercise duration of more than 15% between two consecutive tests separated in time by 1-7 days; angina at rest or unstable angina; anginal attacks that were progressively more frequent, longer lasting, or difficult to relieve; concomitant anti-anginal therapy other than beta-blockers or short-acting nitrates; type II or III AV block; myocardial infarction, CABG, angioplasty, or stroke in the past three months, overt congestive heart failure, hypotension (systolic blood pressure <100 mm Hg); severe renal, hepatic, or hematological disorders; known intolerance to dihydropyridines; any drug known to influence the ST segment; documented left ventricular hypertrophy on echo with typical ECG changes; left bundle branch block; suspected alcohol or drug abuse; pregnancy or women of childbearing age without oral contraceptives; women during lactation; or participation in other studies

Primary Endpoints:

Total exercise time, time to chest pain, and time to 1 mm ST depression during exercise testing results at five weeks; occurrence of chest pain during exercise testing; and adverse events

Secondary Endpoints:

Amount of ST depression at highest comparable workload, amount of maximal ST depression, and rate pressure product during exercise testing at five weeks

Drug/Procedures Used:

Patients were randomized to one of three arms: continuation of metoprolol ER alone (control group, 200 mg or 100 mg daily), dual therapy with metoprolol ER plus felodipine ER (10 mg daily), or replacement of metoprolol with felodipine alone. The patients were followed for five weeks. Bicycle exercise testing was performed at the end of week two and week five.

Concomitant Medications:

Aspirin (84% control vs. 89% dual therapy vs. 84% felodipine alone). Medical treatment for hypercholesterolemia (specific drugs not reported, 35% control vs. 30% dual therapy vs. 35% felodipine alone). Long acting nitrates were not allowed.