Therapeutic implications of dynamic coronary stenosis in patients with single vessel coronary artery disease.

Ten patients with proven single-vessel coronary artery disease and a positive exercise test for ischaemia were investigated to establish the importance and therapeutic implications of dynamic coronary stenosis in such patients. All patients interrupted their anti-anginal therapy and under took serial exercise testing in an attempt to identify variability in the ischaemic threshold. Ergonovine testing was performed in nine patients and all underwent 48 h of ambulatory ST segment monitoring while treatment was discontinued. Patients then entered a randomized double-blind study of atenolol and nifedipine; treadmill exercise testing and 48 h of ambulatory ST segment monitoring were performed at the end of each treatment phase. Six (60%) patients showed evidence of variability in coronary vasomotor tone four of whom developed significant ST segment changes during administration of ergonovine; a further two had greater than 30% variability in time to onset of ischaemia during serial treadmill exercise testing. Atenolol significantly increased the time to ischaemia on exercise testing, both in the group as a whole and in the subgroup with evidence of altered vasomotor tone when compared with no therapy, and led to a non-significant reduction in the frequency and duration of ischaemia during the patients' daily lives. Nifedipine, conversely, did not significantly increase time to ischaemia on exercise testing or reduce the frequency or duration of ambulatory ischaemia in either the whole group or the subgroup. With evidence of altered vasomotor tone when compared to no therapy however it was beneficial in terms of reduction in chest pain and requirement for glyceryl trinitrate during daily life.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian variation of total ischaemic burden and its alteration with anti-anginal agents.

6264 hours of ambulatory ST segment monitoring of 150 unselected patients with proven coronary artery disease, who were off all routine anti-anginal treatments, showed 598 ischaemic episodes, of which 446 (75%) were silent (symptom-free). Most (68%) ischaemic episodes occurred between 0730 and 1930, with a peak in the morning and a lesser peak in the evening. Two subgroups were studied further in double-blind controlled trials: 33 patients had a total of 1313 hours of ST segment monitoring while treated with nifedipine; and 41 patients a total of 1581 hours while treated with atenolol. Nifedipine did not alter the circadian pattern of ischaemic episodes; atenolol abolished the morning peak, and the peak incidence of ischaemia then occurred in the evening. Circadian patterns for total duration of ischaemic episodes corresponded closely to those of episodes of ischaemia, and were similarly altered by treatment. The circadian pattern of silent ischaemic episodes and their total duration were very similar to those of total ischaemia for the group as a whole and the different subgroups. This circadian distribution of ischaemic episodes and the observed changes with treatment resemble the reported circadian variation of acute myocardial infarction and sudden death.

Comparative antianginal effects of nisoldipine and nifedipine in patients with chronic stable angina.

The acute antianginal effects of 5 mg and 20 mg nisoldipine were compared with 20 mg nifedipine and placebo. Maximal treadmill exercise testing was performed before and 3 hours after drug administration in 10 patients with chronic stable angina. Resting heart rate and systolic blood pressure were unchanged following low-dose nisoldipine, but 20 mg nisoldipine and 20 mg nifedipine increased heart rate and decreased systolic arterial pressure (p less than 0.05). Time (in seconds) to the onset of 0.1 mV ST segment depression was significantly prolonged after 5 mg nisoldipine (+60 +/- 53; p less than 0.05) and 20 mg nisoldipine (+100 +/- 78; p less than 0.01) but not after 20 mg nifedipine (+48 +/- 131; p = NS). Total exercise duration increased significantly following 5 mg and 20 mg nisoldipine (p less than 0.01 and p less than 0.001, respectively) but only slightly following nifedipine (p = NS). The maximal rate-pressure product was increased to a similar degree following doses of both nisoldipine and nifedipine (p less than 0.05). Nisoldipine is an effective antianginal agent which performs well in comparison to nifedipine.