concentrations in the therapeutic range were associated with an increased frequency of hospitalizations for cardiovascular events other than HF and an increased risk of death due to arrhythmias or myocardial infarction89. These effects neutralized any benefit on survival that might otherwise have been seen as a result of the favorable effect of the drug on HF. These observations have raised the possibility that digoxin doses and serum digoxin concentrations that are generally considered by physicians to be safe may adversely affect the heart.
Interventions to be Considered for Use in Selected Patients
Controlled clinical trials have shown some interventions to be useful in a limited cohort of patients with HF. Several of these agents are undergoing active investigation in large- scale trials to determine whether their role in the management of HF might be justifiably expanded.
Isosorbide dinitrate was one of the first vasodilator agents reported to be useful for chronic therapy of HF. Nitrate therapy may decrease symptoms of dyspnea at night and during exercise and may improve exercise tolerance in patients who have persistent limitation despite optimization of other therapies90.
The only common side effects of nitrate therapy are headaches and hypotension. In clinical use, nitrates are frequently prescribed to patients with persistent congestive symptoms. Nitrates are predominantly potent venodilators that also have effects on arterial tone, particularly when systemic vascular resistance is severely elevated.
HYDRALAZINE AND ISOSORBIDE DINITRATE
Hydralazine is an arterial vasodilator with relatively little effect on venous tone and cardiac filling pressures. In addition to its direct vascular actions, hydralazine in theory may interfere with the biochemical and molecular mechanisms responsible for the progression of HF and the development of nitrate tolerance.
Although very limited data are available regarding the use of hydralazine alone in HF, a combination of hydralazine and isosorbide dinitrate has been used in different studies.
89 The effect of digoxin on mortality and morbidity in patients with heart failure. The Digitalis Investigation Group. N Engl J Med 1997;336:525-33.
90 Elkayam U, Johnson JV, Shotan A, et al. Double-blind, placebocontrolled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition. Circulation 1999;99:2652–7.