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Combination therapy with isosorbide dinitrate: current status and the future.

Abstract

The excellent safety and predictable efficacy of isosorbide dinitrate (ISDN) have been demonstrated repeatedly during the past 25 years in a number of studies in which the agent has been used alone or in combination with other antianginal agents. Clinical studies to investigate the additive or synergistic effect of ISDN have been difficult to conduct because of the complexity of protocol design and length of studies required. However, combination therapy is well accepted in the clinical practice of medicine and cardiology and is used to obtain additive therapeutic effects while minimizing the side effects. The addition of ISDN not only to other standard and proven antianginal agents but also to calcium antagonists should prove to be a fruitful area for further clinical research benefiting patients with angina pectoris (caused by either coronary artery spasm or occlusive coronary artery disease), hypertension, and congestive heart failure. Noncardiovascular uses of ISDN may include the treatment of hyperspasticity of other smooth muscle beds, such as esophageal spasm and achalasia.

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BibTeXRIS

J S Schroeder. 1985. Combination therapy with isosorbide dinitrate: current status and the future.. https://doi.org/10.1016/0002-8703(85)90503-4

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Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris.

OBJECTIVE: Ischemic preconditioning is an increased tolerance to myocardial ischemia during the second of two consecutive exercise tests. ATP-sensitive K(+) channel blockers, such as glinides and sulfonylurea drugs, can induce loss of ischemic preconditioning. This study aimed to investigate the effects of repaglinide, a hypoglycemic agent with an affinity for myocardial ATP-sensitive K (+)channels, on the results of consecutive exercise tests in patients with diabetes and multivessel coronary artery disease. METHODS: Forty-two patients with type 2 diabetes and chronic stable angina pectoris, and two-vessel or three-vessel disease participated in this study. The patients underwent two consecutive treadmill exercise tests (phase 1). On the day after these exercise tests, 2 mg of oral repaglinide was given to the patients. One week later, two exercise tests were repeated consecutively (phase 2). RESULTS: All patients achieved 1.0-mm ST-segment depression during the four exercise tests (T1, T2, T3, and T4). In phase 2, seven patients improved in time to onset of 1.0-mm ST-segment depression. The worsening of the time to onset of 1.0-mm ST-segment depression in phase 2 demonstrated ischemic preconditioning block in 83.3% of patients (P=0.0001). Even the postexercise electrocardiographic parameters (ST-segment depression morphology and magnitude and arrhythmias) were significantly different between the groups with and without pharmacologic ischemic preconditioning block (P=0.031). CONCLUSIONS: Repaglinide, an oral hypoglycemic agent with ATP-sensitive K(+) channel-blocker activity, eliminated the myocardial ischemic preconditioning in patients with coronary disease and diabetes.

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