Effects of Oral Nisoldipine on Transient and Exercise-Induced Ischaemia in Patients with Coronary Heart Disease

Abstract

The new dihydropyridine derivative nisoldipine seems to have several pharmacokinetic advantages over the calcium channel blockers available at the moment. Therefore, we started a study on its efficacy in reducing ischaemia in patients with coronary heart disease, both under exercise conditions and during normal daily life. The study has a double-blind, crossover, placebo-controlled design with an acute phase followed by a 3–4-week observation period. During the first 4 days the patients received either 10 mg nisoldipine or placebo orally, once daily, either in the order PNPP or PPNN. During these days the patients were continuously on Holter monitoring for ischaemic ST-segment changes and underwent two exercise tests, one with placebo, one with nisoldipine. After a 3–4-week observation period on 10 mg nisoldipine once daily, patients were given repeat Holter monitoring and exercise testing. The inclusion criteria for the study were definite coronary heart disease (by coronary angiography) and rest angina (12 patients). Five patients had more than three ischaemic episodes during the first 24 h on placebo. During the acute phase nisoldipine showed a marked reduction in the number and duration of episodes in three patients, while in the other two the number of episodes was unchanged. In all five, however, the number of episodes was reduced during the monitoring period after 3 weeks of nisoldipine. Only one patient had severely impaired exercise tolerance which improved markedly with nisoldipine (from 3 to 15 min and from 25 to 75 W). These preliminary results allow no conclusions, but in some patients a clear-cut and sustained beneficial effect of nisoldipine could be observed. Our study demonstrates again the difficulties in selecting patients for this type of study, in which only severe disease allows documentation of treatment effects, and yet treatment with placebo controls seems mandatory.