Combination therapy with calcium-entry blockers and beta-adrenoceptor antagonists in hypertension

The use of more than one drug to control blood pressure may be necessary in up to 50% of hypertensive patients seen in clinical practice. A rational basis for combination therapy includes 1) the use of drugs that act on different physiological systems involved in blood-pressure control and 2) using a second drug to counteract reflex responses, which may limit the effectiveness of the first, and, 3) as is less commonly practiced, the use of low doses of two drugs that act on the same or different physiological systems to avoid the side effects encountered with higher doses of single agents. The hemodynamic effects of calcium-entry blocking drugs and beta-adrenoceptor blockers are complementary and synergism might be anticipated, particularly with the dihydropyridines and beta-blockers, since the latter prevent the short-term reflex increase in sympathetic activity occurring as a consequence of vasodilation. Although there are many studies advocating the benefits of such combinations, caution is required with combinations of beta-blockers and verapamil or diltiazem because of potential cardiac depressant effects resulting from the more complex effects of these calcium-channel blockers on cardiac myo-cytes and conducting tissue. Such problems would be more likely to be encountered in patients with long-standing hypertension and in whom poor left ventricular function and coro-nary artery disease may be present.