Calcium antagonists in patients with heart failure. A review

The presence of calcium ions is essential to the normal function of the cardiovascular system. Drugs such as calcium antagonists can modulate the interaction between these ions and specific cells at different levels, interfering with myocardial contraction and relaxation, vascular tone, specific conduction tissues and neuromuscular function. Vascular beds play a crucial role in adjustment of myocardial function to different body oxygen requirements; compensatory mechanisms in congestive heart failure (CHF) involve the vascular system to a large extent and paradoxically may worsen myocardial performance. Vasodilating drugs represent an important step forward in achieving better symptomatic results in CHF patients, and may also increase their survival. Of the different classes of vasodilator drugs calcium antagonists may represent an attractive alternative due to their anti-ischaemic and antiarrhythmic effects. Despite the overall good response to the acute use of these drugs in CHF, long term studies in which first generation calcium antagonists (nifedipine, diltiazem, verapamil) were used have produced disappointing results. Their main drawbacks were negative inotropism, lack of preload reduction and activation of neurohormonal mechanisms with a subsequent adverse effect on cardiovascular function, the latter effect being the most significant. A few long term studies, of between 1 and 52 months, have not demonstrated a consistent improvement in functional class in spite of apparently good initial results. The second generation of calcium antagonists have more potent and selective vasodilating properties with less negative inotropic effects; these properties might justify their use in the therapy of CHF, but no clear recommendations can be given due to the lack of large, long-term, controlled studies. Overall, the existing clinical trials with calcium antagonists in CHF have not proved the superiority of this group of drugs when compared to other vasodilators. If the aetiology of CHF is related to the presence of coronary artery disease or arterial hypertension, calcium antagonists might be considered as additional therapeutic options. Diastolic dysfunction may be corrected or improved and coronary tone may be diminished, both of which may lead to a better myocardial oxygen supply. Systolic myocardial function must be evaluated in CHF patients before starting therapy with calcium antagonists in order to avoid possible deleterious effects. Further studies may shed more light on this matter and may indicate decisively whether or not calcium antagonists should play a role in the therapeutic pharmacological arsenal of selected CHF patients.