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Studies of the efficacy of molsidomine, previously performed on our service, demonstrated that a clear antianginal effect in the longterm treatment of angina pectoris could only be achieved with a regimen of the standard 2 mg dose when given six times daily. Consequently, since a mode of administration with a longer duration of action was implicitly desirable, the present study, carried out in eleven patients with coronary artery disease and stable, exertional angina pectoris, was undertaken to assess the antiischemic effects of 8 mg molsidomine in sustained-release form as compared with the standard 2 mg formulation according to a double-blind, randomized, crossover, placebo-controlled protocol. Additionally, plasma concentrations of molsidomine were determined to elucidate the bioavailability as well as possible correlations between plasma concentrations and antiischemic effect. As compared with placebo, after administration of 8 mg molsidomine sustained-release there were reduction in the ST-segment depression at one, three, five and eight hours of 74% (p less than 0.001), 61% (p less than 0.001), 44% (p less than 0.025), and 31% (p less than 0.01), respectively; after 2 mg molsidomine, 74% (p less than 0.001), 37% (p less than 0.025), 7% (ns) and 6% (ns), respectively. Analysis of the response of the ST-segment in the individual patients showed an unequivocal antiischemic effect with a reduction in ST-segment depression of at least 1 mm after 8 mg molsidomine sustained-release at the specified points in time in ten, five, six and four patients, respectively, and after 2 mg molsidomine in nine, five, one and no patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was undertaken to determine whether an effective antianginal treatment without tolerance development can be carried out with intermittent nitrate administration on a regimen with a single daily dose of 120 mg isosorbide dinitrate (ISDN) in sustained-release form (SR), as well as whether the concomitant administration of 100 mg atenolol or 100 mg atenolol and 20 mg nifedipine renders an additive antiischemic effect. In two independently performed investigations, the duration of action of a single dose of 120 mg ISDN SR was assessed after its initial administration in addition to the anti-ischemic effect during long-term treatment, each according to a randomized, double-blind, crossover, placebo-controlled protocol in a total of 15 patients with angiographically-documented coronary artery disease, stable angina pectoris and reproducible ST-segment depression during exercise. The test phases of four weeks each were separated by one week placebo phases. After completion of the study, for a further eight weeks, 120 mg ISDN SR was given together with 100 mg atenolol in the morning. Exercise testing was carried out after four weeks of treatment in a control period before and at two hours after administration of 120 mg ISDN SR with 100 mg atenolol as well as after another four weeks in a control period before and after concomitant administration of 120 mg ISDN SR, 100 mg atenolol and 20 mg nifedipine in sustained release form.(ABSTRACT TRUNCATED AT 250 WORDS)

Within a relatively short period of time, nitroglycerin patches have come into widespread use for treatment of coronary artery disease in the absence of sufficient clinical data in support of their efficacy. Presently, there is still considerable controversy regarding the extent and duration of action as well as the dosage requirements. Accordingly, a study was carried out in six patients with angiographically-documented coronary artery disease, stable exercise-induced angina pectoris and reproducible ST-segment depression to analyze the effects of nitroglycerin patches, formulated to deliver 5 mg, 10 mg, 20 mg as well as 30 mg per 24 hours, respectively, on the extent of ST-segment depression. In a further study, the extent and duration of antianginal and anti-ischemic effects of nitroglycerin patches delivering 30 mg/24 hours were investigated in ten patients according to a randomized, double-blind, crossover placebo-controlled protocol. In seven of these patients, testing was again performed at 2.5 hours after repeated application (second application at 24 hours) (Figure 1). Nitroglycerin patches delivering 5 mg, 10 mg, 20 mg as well as 30 mg/24 hours, respectively, led to significant reductions in ST-segment depression at 2.5 hours of 59% (range 25 to 100%; p less than 0.025), 63% (0 to 100%, p less than 0.01), 77% (50 to 100%, p less than 0.001) as well as 82% (50 to 100%, p less than 0.005) as compared with control values (Figure 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Nisoldipine (Bay K5552), a newly-developed dehydropyridine derivative with calcium antagonistic properties, was found to have a duration of action twice as long as its parent compound, nifedipine, in laboratory experiments. To evaluate the anti-ischemic potency and duration of action, the effects of 10 mg nisoldipine after acute administration and at the end of three weeks of treatment with 10 mg twice daily were compared with those of 120 mg verapamil three times daily in a double-blind, randomized, crossover, placebo-controlled study. In twelve patients with angiographically-documented coronary artery disease and stable exertional angina pectoris, bicycle ergometry was performed before and at three and seven hours after medication on the first and 21st days of the three respective treatment phases. The control value at 8 a.m. on the 21st day corresponded with the ten-hour value on the 20th day of treatment. Between the three treatment phases, there was a one-week wash-out period during which the patients received placebo three times daily. At the time of the ergometric studies, blood was drawn for determination of verapamil plasma concentrations and, additionally, each patient recorded anginal attacks and nitrate consumption. Analysis was carried out for ST-segment depression in each patient at the highest comparable workload achieved in all treatment phases, the time to onset of 1 mm ST-segment depression as well as the response of the heart rate, systolic arterial blood pressure and the heart rate-blood pressure double-product both at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)