Abstract
We investigated the possibility that high dosages (480 mg/d) of isosorbide dinitrate might reduce the frequency of angina attacks in selected patients who had not responded to low dosages of the drug (40 mg/d), and that the patients could tolerate the high levels of medication and maintain their responsiveness over the long term. In the single-blind phases of this trial 24 patients with grade 3 stable angina pectoris were given a placebo for 4 weeks and then increasing doses of isosorbide dinitrate for a further 6 weeks. The 19 patients who both responded to and tolerated high doses of the drug kept taking 480 mg/d for an average of 1 year. The average weekly rate of angina attacks fell by 74%, from 6.05 in the placebo phase to 1.6 during long-term active treatment (p less than 0.01). Nitroglycerin consumption decreased accordingly. The patients' assessments of their levels of activity and well-being and their angina thresholds showed improvement among most of them. The trend of angina frequency was stable in 12 cases, downward in 6 and upward in only 1 case. Exercise performance as evaluated by a graded treadmill test showed a small but nonsignificant improvement of 18%. It was concluded that some patients who do not respond to the antianginal action of low-dosage isosorbide dinitrate and cannot be given beta-blockers may respond to high dosages and tolerate them for over a year. Isosorbide dinitrate may be clinically useful in patients with coronary heart disease even though their exercise performance is not significantly improved.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Biron P., Tremblay G. Acebultolol: basis for the prediction of effect on exercise tolerance. Clin Pharmacol Ther. 1976 Mar;19(3):333–338. doi: 10.1002/cpt1976193333. [DOI] [PubMed] [Google Scholar]
- Roy P., Day L., Sowton E. Effect of new beta-adrenergic blocking agent, Atenolol (Tenormin), on pain frequency, trinitrin consumption, and exercise ability. Br Med J. 1975 Jul 26;3(5977):195–197. doi: 10.1136/bmj.3.5977.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shane S. J., Iazzetta J. J., Chisholm A. W., Berka J. F., Leung D. Plasma concentrations of isosorbide dinitrate and its metabolites after chronic high oral dosage in man. Br J Clin Pharmacol. 1978 Jul;6(1):37–41. doi: 10.1111/j.1365-2125.1978.tb01679.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thadani U., Fung H. L., Darke A. C., Parker J. O. Oral isosorbide dinitrate in angina pectoris: comparison of duration of action an dose-response relation during acute and sustained therapy. Am J Cardiol. 1982 Feb 1;49(2):411–419. doi: 10.1016/0002-9149(82)90518-5. [DOI] [PubMed] [Google Scholar]
- Tremblay G., Biron P., Proulx A. Dissociation between clinical and exercise responsiveness to beta-blockade in angina. Int J Clin Pharmacol Biopharm. 1978 Nov;16(11):508–512. [PubMed] [Google Scholar]