Calcium channel antagonism and beta blockade in combination—A therapeutic alternative in cardiovascular disorders. A review

Abstract

Calcium-channel antagonists and beta-adrenergic blocking agents have become important modalities in the cardiovascular therapeutic armamentarium. These drugs are often administered as monotherapy to a wide range of cardiological patients with angina pectoris, hypertension, arrhythmias, congestive heart failure, and other diseases. Since within each class these drugs exhibit pharmacologic differences, it follows that their effectiveness varies in different disease states and that they exhibit a wide variety of side effects. In an attempt to optimize therapy, the individual drugs from these two classes can be combined; and the efficaciousness and side-effect profile of various combinations between calcium-channel antagonists and beta blockers are discussed in this review. Recommendations as to which patients may benefit from a combination and as to which patients may be harmed by the combination therapy will be made. Very few studies have compared the safety and efficacy of a single agent with the combination and with placebo in a controlled randomized fashion. To determine which therapy is superior and to determine which combination one should recommend under what circumstances, such placebo-controlled, randomized trials are a necessity, and will hopefully be performed although the complexity is enormous.

Combination Therapy With Beta‐adrenergic Blockade and Amlodipine as Second Line Treatment in Essential Hypertension

“…Dihydropyridine calcium antagonists can be safely combined with beta‐blockers. Among these drugs, amlodipine seems to be particularly indicated for combination therapy with atenolol: the reciprocal reduction of side‐effects of each of the two drugs confirms the rationality of this combination 17 . In addition, both short‐ and long‐term studies show that this combination therapy is effective in patients with ischaemic heart disease, regardless of blood pressure values 18–20 …”

“…It is also important that possible undesirable effects of the first drug are minimised by the other drugs (Table 3) 16 . Therefore the choice of the second drug depends largely on the nature of the first 17 …”

“…The combination of atenolol plus amlodipine induces, on the one hand, beta‐blocker effects such as decreased cardiac output, inhibition of the baroceptor reflex and renin release, and blunted reaction to catecholamines during exercise and stress; and, on the other, calcium antagonist effects such as peripheral vasodilatation with a slight natriuretic effect 17,18 …”

“…Therefore the choice of the second drug depends largely on the nature of the first. 17 In order to reduce side-effects and improve blood pressure control, combination therapy has been widely accepted but inadequately tested. 17 Available fixed combinations include diuretics plus beta-blockers, diuretics plus ACE inhibitors, and diuretics plus angiotensin II antagonists.''…”

Development of a Multiaction Beta Blocker

“…It has been shown that the combi nation of a beta-blocking agent and a Ca2+ antagonist is more effective than the individ ual components [7,8]. Several newer combi nations of angiotensin-converting enzyme (ACE) inhibitors and beta blockers or Ca2+ antagonists have been tested successfully [9].…”