Copyright © 1993 by the European Society of Cardiology.
© 1993 The European Society of Cardiology
Calcium antagonists or β-blockers in chronic ischaemic left ventricular dysfunction?
Department of Physiology and Pharmacology, Division of Cardiology, University ofLouvain Brussels, Belgium
Correspondence: Dr H. Pouleur, University of Louvain, av Hippocrate 55/5560, B-1200 Brussels, Belgium.
Angina pectoris in patients with severe left ventricular dysfunction (LVD), with or without heart failure, is important clinically and socioeconomically. In the Studies of Left Ventricular Dysfunction (SOLVD), more than 36% of the patients had angina pectoris. Although angiotensin-converting enzyme (ACE) inhibitors improve survival and reduce the incidence of new, acute ischaemic events in these patients, they have no significant impact on the incidence of anginal attacks. Treatment of these patients must, therefore, primarily rely on nitrates, β-blockers and calcium channel blockers. The β-blockers, by lowering heart rate, improve the balance between myocardial oxygen supply and demand during exercise, and are among the most effective anti-anginal agents available. In addition, by reducing resting heart rate and by preventing excessive catecholamine stimulation of the myocardium, β-blockers may slow the progression of ischaemic LVD. This may contribute to the improved survival observed when these agents are used following myocardial infarction. By reducing cardiac sympathetic stimulation, however, β-blockers may depress right and left ventricular pump function. This depression is generally of no clinical consequence when the ejection fraction remains above 40%, but when the ejection fraction is below 35%, only 30% of patients without heart failure and 10% of those with heart failure seem to tolerate a full dose of β-blocker. This limits their therapeutic use in angina in this setting. Moreover, β-blockers do not act on the mechanisms underlying some anginal attacks, namely the vasoconstriction of large coronary vessels at the level of atherosclerotic plaques and the reflex vasoconstriction of small coronary arterioles.
Calcium channel blockers may improve myocardial oxygen supply by relieving inappropriate vasoconstriction, and may also reduce oxygen demand by lowering blood pressure. These agents might be considered as an alternative to β-blockers in the management of these patients. Unfortunately, calcium antagonists activate several neurohumoral compensatory mechanisms and produce a dose-dependent depression in myocardial performance, which far exceeds that caused by β-blockade alone. Their use has, therefore, resulted in worsening the symptoms of congestive heart failure and in precipitating heart failure in previously asymptomatic subjects. Furthermore, these drugs provide no survival benefit.
In conclusion, β-blockers appear to be the drug of first choice in treating angina pectoris in patients with severe ischaemic LVD. If the drug is not well tolerated, or if angina pectoris is not well controlled, a calcium antagonist may be considered with caution. The new generation of dihydropyridine derivatives, which induce less depression in myocardial performance are probably preferable for this indication to nifedipine or diltiazem. The calcium channel blockers may also be better tolerated when given in conjunction with an ACE inhibitor. There is, however, a clear need for new drugs, for example bradycardic agents or metabolic modulators, to treat myocardial ischaemia in patients with severe LVD.
Key Words: Calcium antagonist • β-blocker • ischaemia • left ventricular dysfunction