Isosorbide-5-mononitrate and atenolol in the treatment of stable exertional angina.

Fourteen men and six women, 48-68 years old, with stable angina and effort-induced ST-segment depression (ST-D) were treated with isosorbide-5-mononitrate (IS-5-MN) 2 x 40 mg/day and/or atenolol (AT) 100 mg/day in a double-blind randomized sequence during two 6-week periods. The patients performed ergometer tests. AT caused more decrease of heart rate at rest and at comparable work-load than IS-5-MN. Blood pressure at rest was in the normal range. Decrease of blood pressure at rest and at effort was similar with both agents. Combined administration of the two drugs was not more effective than monotherapy with AT or IS-5-MN in lowering heart rate and blood pressure. The average ST-D at comparable effort was for placebo 2.3 mm, for IS-5-MN after 2, 4, and 6 weeks, 3, 6, and 12 h, respectively, after medication, 1.4, 1.0, and 1.3 mm, and for AT 1.2, 1.4, and 1.4 mm, respectively. Administration of the drugs together caused additional highly significant reduction of ST-D (0.3-0.9 mm). The results indicate that IS-5-MN and AT have a similar beneficial effect on effort-induced myocardial ischemia, which is enhanced by their combined administration. The drugs alone and in combination are effective for as long as 12 h after administration of IS-5-MN, and 24 h after administration of AT. Moderate signs of tolerance to IS-5-MN were found after 6 weeks of therapy.

Multivariate analysis of the twenty-year follow-up of the Donolo-Tel Aviv Prospective Coronary Artery Disease Study and the usefulness of high density lipoprotein cholesterol percentage.

The aim of this study was to assess the role of high density lipoprotein (HDL)-cholesterol percentage and its relation to other variables assumed to be coronary risk factors. The 20-year follow-up involved 2,633 presumably healthy subjects, 1,308 men and 1,325 women, aged 25 to 69 years at the beginning of the study in 1964. Variables determined at entry examination included total cholesterol, HDL cholesterol, systolic and diastolic blood pressures, body mass index and cigarette smoking. During the 20-year period there were 242 fatal and nonfatal definite coronary events in men, and 108 in women. All variables differed in varying degrees between subjects who did and did not have a definite coronary event. Three multiple logistic regression models revealed that among these variables the most important was HDL-cholesterol percentage, which significantly improved the regression, even after total cholesterol was included with all other risk factors. With the first model, goodness-of-fit tests indicated that predicted values fit the observed values well, even after the first step, if HDL-cholesterol percentage is entered. The second and third models significantly fit the predicted values only after entering the HDL-cholesterol percentages. This means that although all the other variables, including total cholesterol, differed significantly between the affected and nonaffected groups, they were insufficient predictors alone. The results reveal that HDL-cholesterol percentage had the highest predictive value for risk of future coronary disease; it significantly improved the predictive capability of the logistic regression model, even after adjustment for all other mentioned variables.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of isosorbide-5-mononitrate on effort-induced electrocardiographic ischemic changes in patients with angina pectoris.

The efficacy of isosorbide-5-mononitrate 40 mg twice a day was tested in 10 patients suffering from effort-induced angina pectoris. Patients were studied with ergometer testing 6 hours after drug administration on the first treatment day, and again 8 and 12 hours after medication at 3 weeks and 6 months of therapy. At comparable and maximal workloads the patients expressed significantly less ST segment depression on treatment than prior to treatment. No tolerance was observed. Isosorbide-5-mononitrate treatment was demonstrated to have a beneficial effect on exercise tolerance in patients suffering from stable angina in effort.

Relation of serum total cholesterol and high-density lipoprotein cholesterol percentage to the incidence of definite coronary events: twenty-year follow-up of the Donolo-Tel Aviv Prospective Coronary Artery Disease Study.

This 20-year follow-up report presents the incidence of definite coronary events and its relation to serum total cholesterol (TC) and alpha-lipoprotein cholesterol percentage (percentage of serum TC bound with alpha-lipoprotein), now usually called high-density lipoprotein cholesterol percentage (HDL-C%). The cohort consists of 1,454 men and 1,481 women, presumably healthy, aged 35 to 64 years at the time of entrance examination in 1964. During the follow-up period 123 men and 44 women died from coronary disease. Ninety-six men and 42 women had nonfatal myocardial infarctions. The incidence of definite coronary events increased from 6% in men with TC levels of less than 200 mg/dl to 25% in men with levels of more than 264 mg/dl. The corresponding figures in women were 3% and 10%. The incidence of definite coronary events was inversely correlated to HDL-C%. The incidence of definite coronary events in 225 men with HDL-C% of less than 14% was 28%, and in 669 men with HDL-C% of 21% or more, 7%. The corresponding figures in 234 women with HDL-C% of less than 17% was 14%, and in 853 women with HDL-C% of 23% or more, 2%. Two HDL-C% subsets were assessed: "low" and "high" subsets refer to HDL-C% of less than 21% and 21% or more, respectively, in men and less than 23% and 23% or more in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of short- and long-term treatment with transdermally and orally administered nitroglycerin (a double-blind crossover study).

The efficacy of a once daily transdermally applied nitroglycerin system and of sustained release nitroglycerin capsules was assessed by ergometer stress testing in 12 patients with stable angina pectoris in a double-blind crossover study. In the morning the patients received transdermally applied nitroglycerin (TDS) which delivered 5.0 mg nitroglycerin in 24 hours together with a placebo capsule, respectively 1 nitroglycerin (NTR) capsule of 2.5 mg together with a plaster placebo. In the evening the first treatment group received 2 placebo capsules, and the second group 1 NTR capsule and 1 placebo capsule. Each period lasted 14 days. The patients performed a pre-medication ergometer stress test and repeated the test on the first and 14th day of each treatment period, 1 and 24 hours after medication. At the end of the second period all patients continued in an open study with TDS once a day for a further three months. Minor degrees of ST-segment depression, and in fewer patients, were observed at comparable workloads in the treatment tests compared with the pre-medication tests. The improvement after TDS on the first and last day of each period, 1 and 24 hours after medication, was significant and more marked than with NTR. The latter did not reach significance. Furthermore, increase of work capacity and elevation of angina threshold was greater with TDS than with NTR. Similar results were found at the end of the open study after 3 months' treatment with TDS. No development of tolerance was observed.

[Longterm effect and maintenance therapy with cutaneous isosorbide dinitrate in patients with coronary heart disease (author's transl)]. / Langzeitwirkung und Dauertherapie mit kutan appliziertem Isosorbiddinitrat bei Patienten mit koronarer Herzkrankheit.

The aim of this study was to examine the duration of action of a single cutaneous application of a 10% isosorbide dinitrate ointment (ISDN-S) and also to ascertain the possible appearance of nitrate tolerance after 6--8 months' maintenance therapy with ISDN-S. After a single application of the ointment an effect lasting more than 7 hours was confirmed by bicycle ergometry. After longterm therapy an acute test with rapidly acting sublingual ISDN produced an undiminished response thus showing lack of nitrate tolerance.