Randomised Double-Blind Comparison of Isosorbide-5-Mononitrate and Sustained Release Nifedipine in Patients with Stable Exercise-Induced Angina

Abstract

The therapeutic effects of isosorbide-5-mononitrate (IS-5-MN) and sustained release (SR) nifedipine for 2 weeks were, investigated in this double-blind randomised comparative multicentre study in 252 patients with well documented coronary artery disease and stable reproducible exercise-induced angina. After 1 week’s treatment with IS-5-MN 20mg twice daily, 50% of the patients were responders, showing an increase in total exercise time (to onset of moderately severe angina) of ⩾ 20% in comparison with the placebo run-in phase. The corresponding rate after SR nifedipine 20mg twice daily was 45%. By increasing the dose in the nonresponders to 20mg 3 times daily for IS-5-MN and 40mg twice daily for SR nifedipine (double-dummy technique), and continuing lower dose treatment in responders for an additional week, the responder rate increased to 61 and 53%, respectively. Both IS-5-MN and SR nifedipine significantly increased total exercise time, time to angina onset and ⩾ 1 mm ST-segment depression, and significantly reduced the rate-pressure product and ST-segment depression at peak exercise compared with the placebo run-in. However, differences between treatments were not significant. The improvement in quality of life, indicated by the reduction in angina episodes and intake of short-acting nitrates, was similar for the 2 drugs. During IS-5-MN treatment, 8 patients were withdrawn prematurely because of adverse events (7 for headache, 1 for tachycardia, vertigo and dizziness). In the SR nifedipine group, 1 patient withdrew because of headache and tachycardia, and another because of a lack of increase in diastolic blood pressure during exercise. Adverse events were reported more frequently in the IS-5-MN group than in the SR nifedipine group (17 and 3.9%, respectively, for transient headache). The pattern and incidence of all adverse effects were as expected in the 2 active treatment groups. Daily treatment costs for a 20mg twice daily dosing regimen for both drugs in the Federal Republic of Germany was 64% higher for SR nifedipine than for IS-5-MN.