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[The anti-ischemic effect of isosorbide dinitrate alone and in combination with gallopamil and propranolol]
H M Sthler-Klich1, R Hopf, M Kaltenbach
1Abteilung für Kardiologie, Zentrum der Inneren Medizin, Klinikum der J.W. Goethe-Universität, Frankfurt.
Abstract:
In 18 patients (17 male and 1 female, 40 to 63 years old) with coronary heart disease, a randomized double-blind study was carried out to investigate in comparison to placebo, the antiischemic effects of 5, 10 and 20 mg isosorbide dinitrate (ISDN) alone and in combination with gallopamil (G: 25 and 50 mg) or 80 mg propranolol (P: 80 mg) on the ischemic ST-segment-depression in standardized exercise ECGs. ST-depression following administration of ISDN alone was reduced significantly and dose-dependently: following 5 mg from 1.32 +/- 1.14 to 1.0 +/- 0.85 mm (-25.2%; p less than 0.05), 10 mg from 1.17 +/- 0.85 to 0.91 +/- 0.69 mm (-21.7% n.s.) and 20 mg from 1.19 +/- 0.5 to 0.52 +/- 0.57 mm (-53.6%; p less than 0.001). In combination with gallopamil (G: 25 and 50 mg) or propranolol (P) reduction of ST-depression was more pronounced: by 5 mg ISDN with 25 mg G from 1.32 +/- 1.14 to 0.7 +/- 0.71 mm (-46.4%; p less than 0.05), with 50 mg G from 1.32 +/- 1.14 to 0.8 +/- 0.83 mm (-38.8%; p less than 0.01), with 80 mg P from 1.32 +/- 1.14 to 0.28 +/- 0.35 mm (-79.5% p less than 0.01), by 10 mg ISDN combined with 25 mg G from 1.17 +/- 0.85 to 0.69 +/- 0.6 mm (-40.7%; p less than 0.05), with 50 mg G from 1.17 +/- 0.85 to 0.66 +/- 0.62 mm (-43.5%; p less than 0.05), with 80 mg P from 1.17 +/- 0.85 to 0.64 +/- 0.78 mm (-46.4%; p less than 0.01), and by 20 mg ISDN with 25 mg G from 1.19 +/- 0.5 to 0.42 +/- 0.43 mm (-62.6%; p less than 0.001), with 50 mg G from 1.19 +/- 0.5 to 0.39 +/- 0.45 mm (-65.2%; p less than 0.001) and with 80 mg P from 1.19 +/- 0.5 to 0.05 +/- 0.16 mm (-95.8%; p less than 0.001).
Insights
Isosorbide dinitrate (ISDN) effectively reduced ischemic ST-segment depression in coronary heart disease patients. Combinations of ISDN with gallopamil or propranolol demonstrated even more pronounced anti-ischemic effects, particularly at higher doses.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Coronary heart disease (CHD) remains a leading cause of mortality worldwide.
- Anti-ischemic therapies are crucial for managing CHD symptoms and improving patient outcomes.
Purpose of the Study:
- To evaluate the anti-ischemic effects of isosorbide dinitrate (ISDN) alone and in combination with gallopamil or propranolol in patients with CHD.
- To assess the dose-dependent efficacy of ISDN and its synergistic effects with other cardiovascular medications.
Main Methods:
- A randomized, double-blind, placebo-controlled study involving 18 patients with CHD.
- Standardized exercise electrocardiograms (ECGs) were used to measure ST-segment depression.
- Patients received varying doses of ISDN (5, 10, 20 mg) alone or in combination with gallopamil (25, 50 mg) or propranolol (80 mg).
Main Results:
- ISDN alone significantly reduced ST-segment depression in a dose-dependent manner, with the 20 mg dose showing the greatest effect (-53.6%).
- Combinations of ISDN with gallopamil or propranolol resulted in more pronounced reductions in ST-depression.
- The combination of 20 mg ISDN with 80 mg propranolol achieved the most significant reduction in ST-depression (-95.8%).
Conclusions:
- Isosorbide dinitrate demonstrates significant dose-dependent anti-ischemic effects in patients with coronary heart disease.
- Combining ISDN with gallopamil or propranolol enhances its anti-ischemic efficacy, suggesting potential for improved therapeutic strategies in CHD management.