The efficacy of
isosorbide dinitrate (ISDN) in variant angina is enhanced by the addition of a
calcium antagonist. A prospective double-blind, crossover trial of ISDN, 40 to 120 mg/day, and
nifedipine, 40 to 120 mg/day, in 19 patients with variant angina and various degrees of
coronary atherosclerosis showed that although both agents were equally effective in controlling angina of vasospastic origin, some patients responded better to one or the other
drug. Such response could not be predicted by demographic factors, ECG changes, or degree of
coronary atherosclerosis. Since quantitative angiography done in a similar group of patients showed that intracoronary
nitroglycerin, 200 micrograms, was a more potent
vasodilator than sublingual
nifedipine, 10 mg (p less than 0.01), the
calcium antagonists may have a different mechanism of preventing variant angina attacks and may act in an additive or synergistic fashion when administered in combination with long-acting
nitrates. Such a combination will increase coronary blood flow, reduce ventricular volume and end-diastolic pressure, and reduce systemic arterial resistance.
Coronary vasospasm may be directly prevented by a general inhibition of smooth muscle contraction by the
calcium antagonist. Clinical studies suggest that combination
therapy significantly improves the long-term prognosis of patients with variant angina and reduces the need for bypass surgery. Thus combining ISDN with a
calcium antagonist is a rational and effective treatment for variant angina.