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-ischaemic 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 possible dihydropyridines-induced reflex sympathetic activation. Despite these mechanistic considerations the results of clinical trials are not homogeneous. Differences in the assessment of the beta blocker-dihydropyridines connection are due to differences in trial design, dosage and formulation of both dihydropyridines and beta-blockers, and in baseline characteristics of the study population. The predominant finding is that a combination of a dihydropyridines and a beta blocker is not superior to either drug alone as a first step treatment of unselected patients with stable or unstable angina. In contrast, combination therapy is often efficacious when residual ischaemia is present under dihydropyridines 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 limit its usefulness, especially in elderly patients with conduction disturbances.