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Duration of effects of isradipine during twice daily therapy in angina pectoris
U Thadani1, S Chrysant, J Gorwit
1University of Oklahoma, Oklahoma City.
Insights
Isradipine, a calcium channel blocker, significantly improved exercise duration and time to ST-segment depression in patients with chronic stable angina. This study highlights isradipine
Area of Science:
- Cardiology
- Pharmacology
Background:
- Isradipine is a 1,4 dihydropyridine calcium channel antagonist.
- It is an approved antihypertensive agent with coronary artery dilating properties.
- Its antianginal effects in chronic stable angina pectoris require further documentation.
Purpose of the Study:
- To evaluate the duration of effects and safety of isradipine 10 mg twice daily (bid) in male patients with chronic stable angina pectoris.
- To assess isradipine's impact on exercise tolerance and time to ischemic endpoints.
Main Methods:
- Placebo-controlled, double-blind, parallel-group study design.
- Seventy-two patients with chronic stable angina underwent exercise testing.
- Patients were randomized to receive either placebo or isradipine 10 mg bid for 2 weeks, with exercise tests conducted at various time points.
Main Results:
- Isradipine significantly increased exercise duration compared to placebo at 3 and 8 hours post-dose.
- Time to 1-mm ST-segment depression also significantly increased at 3 hours post-dose with isradipine.
- No significant increase in exercise tolerance was observed at 12 hours post-dose; rate-pressure double product remained unaffected.
- A correlation was found between increased exercise time and plasma isradipine concentration.
Conclusions:
- Isradipine 10 mg bid demonstrates significant antianginal effects in patients with chronic stable angina.
- The antianginal benefits of isradipine are most pronounced within 8 hours of dosing.
- Isradipine was well-tolerated, with no ischemic complications reported.
Abstract:
Isradipine, a 1,4 dihydropyridine calcium channel antagonist, is a potent coronary artery dilator that increases coronary blood flow with little effect on cardiac contractility. Isradipine is an approved antihypertensive agent, but its antianginal effects have not been well documented. In this placebo-controlled, double-blind, parallel-group design study we evaluated the duration of effects and safety of isradipine 10 mg bid in male patients with chronic stable angina pectoris. Seventy-two patients experiencing moderately severe angina between 3 and 7.5 minutes during a standard Bruce exercise test received placebo in a single-blind manner for 8-14 days. Sixty-one of these patients had reproducible treadmill exercise test results on three consecutive occasions and underwent further exercise tests at 3, 8, and 12 hours after a placebo period. Patients were then randomized (double blind) to either placebo or isradipine 10 mg bid for 2 weeks. Symptom-limited exercise tests were repeated predose and at 3, 8, and 12 hours after the 0800 hour dose dosing. Exercise duration increased significantly from baseline (last qualifying test during the single-blind placebo therapy, i.e., 0800 hours predose at visit 4) in the isradipine group compared to the placebo group prior to the administration of the 0800 hour dose (i.e., 12 hours after the 2000 hour dose) by 51 vs. 18 seconds, p = 0.04; and after the administration of the 0800 hour dose at 3 hours by 78 vs. 29 seconds, p = 0.005; and at 8 hours by 54 vs. 18 seconds, p = 0.04. Similarly, statistical significance was achieved when exercise data were analyzed using visit 4 (single-blind placebo therapy) corresponding time points as baseline. At 12 hours after the 0800 hour dose, exercise tolerance did not increase significantly after isradipine compared to placebo. Time to 1-mm ST-segment depression increased significantly after isradipine at 3 hours post 0800 hour dose compared to placebo (87 vs. 7 seconds, p < 0.01) but not at the 0, 8, or 12-hour postdose time points, regardless of which baseline was used. Isradipine therapy did not affect the rate-pressure double product. A significant correlation between the mean increase in total exercise time and mean plasma isradipine concentration was also present (p = 0.0295). During double-blind treatment, drug-related adverse events were experienced by four patients in the isradipine group and two patients in the placebo group. None of the patients experienced ischemic complications during the study.(ABSTRACT TRUNCATED AT 400 WORDS)