PHARMACOLOGICAL AND THERAPEUTIC BASIS FOR COMBINED ADMINISTRATION OF BETA-BLOCKERS AND CALCIUM-CHANNEL BLOCKERS IN THE TREATMENT OF STABLE CHRONIC ANGINA

Pharmacodynamics of beta-adrenergic blockers and dihydropyridines are potentially synergic in the treatment of angina pectoris. The anti-isc haemic effect of beta blockers is mainly the consequence of reductions in heart rate and inotropism, while DHPs promote afterload reduction and coronary vasodilation. Furthermore, beta blockers antagonise the p ossible dihydropyridines-induced reflex sympathetic activation. Despit e these mechanistic considerations the results of clinical trials are not homogeneous. Differences in the assessment of the beta blocker-dih ydropyridines connection are due to differences in trial design, dosag e and formulation of both dihydropyridines and beta-blockers, and in b aseline characteristics of the study population. The predominant findi ng is that a combination of a dihydropyridines and a beta blocker is n ot superior to either drug alone as a first step treatment of unselect ed patients with stable or unstable angina. In contrast, combination t herapy is often efficacious when residual ischaemia is present under d ihydropyridines or beta blocker monotherapy. That this combination is usually well tolerated thus appears to represent a useful treatment of severe angina pectoris. Combination of a non-dihydropyridines calcium antagonist such as diltiazem or verapamil with a beta blocker offers similar synergistic anti-ischaemic effects, but the addition of their negative chronotropic action may lead to severe bradycardia and thus l imit its usefulness, especially in elderly patients with conduction di sturbances.