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

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.