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A number of studies have addressed the response to calcium antagonists, used alone or combined with other therapy, in patients with silent myocardial ischemia (SMI). Nifedipine, the first calcium antagonist to be studied, was shown to be superior to pindolol in patients with effort angina. Although both nifedipine and diltiazem significantly reduced episodes of ST depression, compared with placebo, in patients with stable effort angina, the addition of nifedipine to diltiazem removed the beneficial effect of diltiazem in another study. Studies have shown a reduced incidence of ischemic episodes during nicardipine treatment in patients with ambulatory ischemia, predominantly SMI, and rest angina due to coronary artery spasm. Other workers similarly reported that verapamil was superior to both placebo and propranolol in reducing painful and painless ischemia in patients with angina at rest. It has been demonstrated that, compared with placebo, nifedipine reduced ischemic episodes by 50% and also markedly reduced total ischemic time in totally asymptomatic men with coronary artery disease and SMI. It was suggested that the well-documented increase in SMI occurring between 0600 and 1200 h was reduced, but not eliminated, by nifedipine. Diltiazem may also attenuate the circadian variation in SMI. Nifedipine has been shown to be particularly effective in SMI when combined with a β-blocker. This has been substantiated in a large group of patients; both drugs reduced the number of episodes of SMI when used as mono-therapy, and the combination decreased the incidence by 95%. These findings collectively indicate that calcium antagonists are effective in reducing or preventing SMI. It would appear that the best results are obtained by using a calcium antagonist that can be combined safely with β-blocker therapy.