β-Blockers and Calcium Antagonists in Angina Pectoris

Summary

In coronary heart disease, β -blockers are beneficial because they limit the increase in heart rate and blood pressure during exercise, and calcium antagonists are useful because they reduce myocardial oxygen demand. Many different pharmacological combinations of a β -blocker and a calcium antagonist are possible, and β-blockade may ameliorate reflex tachycardia induced by peripheral vasodilatation due to calcium antagonists, therefore enhancing the benefit.

Studies have shown that combination therapy with propranolol and nifedipine, verapamil or diltiazem has greater antianginal efficacy based on symptomatic and objective assessment than either agent alone. A similar result has been reported for nifedipine or verapamil combined with atenolol. In combination, atenolol and nifedipine did not depress cardiac output or change the left ventricular ejection fraction (LVEF) at rest. During exercise, atenolol alone resulted in a reduced LVEF response in most patients but the combination did not adversely affect left ventricular function. Nifedipine alone did not significantly change LVEF. When verapamil was combined with atenolol, resting ejection fraction fell, indicating a deterioration in cardiac function.

Nifedipine and propranolol combined do not change heart rate significantly. Verapamil and atenolol both reduce resting heart rate and their combination has a greater effect; a combination of propranolol and diltiazem also reduces heart rate to a similar extent. Caution is therefore warranted when prescribing the latter 2 combinations.

An increase in side effects can be expected with combination regimens compared with monotherapy; but with the nifedipine-atenolol combination the calcium antagonist can alleviate β-blocker-induced effects by its vasodilator effect, and β-blockers may ameliorate nifedipine-induced palpitations and flushing.

The effect on prognosis of the combination treatment remains an important question. Evidence suggests that β-blockers and calcium antagonists may favourably influence some of the factors important in the development and rupture of atheromatous plaques. However, any theoretical effect must be tested in a large-scale trial. The most complementary combination appears to be a β-blocker with a dihydropyridine, and, arguably, when tachycardia accompanies use of a vasodilator such agents are best used in the presence of β-blockade.