[Efficacy and tolerability of felodipine and nifedipine in stable angina refractory to beta-blocker therapy].

BACKGROUND: Medical therapy of stable angina contemplates beta-blockers as a first line. The combination of dihydropyridines with beta-blocking drugs enhances the effectiveness of both single therapies. Nifedipine, in the usual formulation (AR), is burdened by an unsatisfactory tolerability, and this is the main reason to study new dihydropyridines. AIM: To compare efficacy and tolerability of felodipine ER 10 mg o.d. with that of nifedipine AR 20 mg b.d. in patients with stable angina pectoris refractory to beta-blocker therapy. PATIENTS AND METHODS: Of 15 initial patients, 14 were entirely evaluable for the study, the design of which was double blind, double dummy, random cross over and placebo controlled. All patients showed reproducible threshold of ischemia at exercise testing. In constancy of beta-blocker therapy, they were given placebos for 2 weeks, then one of the active drugs with a placebo of the other one for 4 weeks, followed by the cross-over period of 4 weeks. Efficacy and tolerability of treatments were evaluated by clinical observation and rest and exercise radionuclide angiography. At the end of each individual study, it was decided blindly if and which of the 2 drugs seemed preferable, considering symptoms, undesired collateral effects and the results of exercise procedures. RESULTS: The efficacy on angina of the 2 active treatments was not different. More patients suffered undesired side effects on nifedipine than on felodipine. Left ventricular ejection fraction (LVEF) at rest was 65.3 +/- 4.3% (s.e.) on placebo, 64.6 +/- 2.6% on felodipine and 67.5 +/- 2.5% on nifedipine (p n.s.). A significant reduction in resting LV function (that is, a decrease of LVEF > or = 5%) was observed in 2 patients on felodipine and 3 on nifedipine, but in both groups other 3 patients showed improvement in LVEF. During exercise, LVEF decreased 6.1 +/- 2.0% on placebo and 3.3 +/- 3.2% on nifedipine, while it increased 1.0 +/- 2.6% on felodipine (p < 0.01 vs. placebo). At the end of the study, felodipine was blindly judged superior to nifedipine in 10 patients, nifedipine was superior in 1 case, in the other 3 there was no clear difference (p < 0.02). CONCLUSIONS: In 14 patients with stable angina refractory to beta-blockers, the addition of felodipine or nifedipine has similar antiischemic effects. However, felodipine showed better results in LVEF response to exercise and less side effects, and this leaded to a more frequent blind choice of felodipine versus nifedipine to add to beta-blocker therapy.