Duration of effects of isradipine during twice daily therapy in angina pectoris.

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)

Hypertrophic cardiomyopathy. Evaluation by gated cardiac blood pool scanning.

The gated radionuclide cardiac blood pool scan (GCS) can be used to visualize the entire profile of the interventricular septum and left ventricular contraction. Twenty-two patients with hypertrophic cardiomyopathy, nine with valvular aortic stenosis and six normals, underwent echocardiography and GCS. All patients with hypertrophic cardiomyopathy had asymmetric septal hypertrophy and 14 of 22 had resting systolic anterior motion of the anterior leaflet of the mitral valve on echocardiogram. In eight patients with aortic stenosis with adequate echocardiograms, two had asymmetric septal hypertrophy and none had systolic anterior motion. The GCS demonstrated disproportionate upper septal thickening in 11; septal flattening in 16; cavity obliteration in 17; and a filling defect in the region of the left ventricular outflow tract in 16 of the 22 patients with hypertrophic cardiomyopathy. In the nine patients with valvular aortic stenosis, two demonstrated septal flattening, two cavity obliteration, two an outflow tract defect, and none disproportionate upper septal thickening. Both patients with cavity obliteration demonstrated asymmetric septal hypertrophy on echocardiogram. One normal control patient had septal flattening. Thus the gated cardiac blood pool scan provides an atraumatic technique for the evaluation of patients with hypertrophic cardiomyopathy which complements the echocardiogram.