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Aim: This study was designed to determine whether therapy with a diuretic has antianginal effects in patients with stable angina who are already treated with a traditional antianginal regimen., Methods and Results: Forty patients with chronic stable angina and normal left ventricular function were randomized in a double-blind, placebo-controlled study. Background antianginal therapy included beta blockers (n = 27), calcium channel antagonists (n = 18), and long-acting nitrates (n = 24). Of the patients 30% had diabetes and 75% had a history of hypertension. Patients were treated with a diuretic (hydrochlorothiazide 25 mg plus amiloride 5 mg) or placebo for 21 days. All patients underwent a treadmill exercise test before randomization and at day 21. The primary end point was the change in treadmill walking time until moderate angina. Diuretic therapy was associated with an increase in treadmill walking time of 63 +/- 17 seconds versus 19 +/- 9 seconds in the placebo group (P = 0.026) and reduced ST-segment depression (0.6 +/- 0.2 mm versus 0.1 +/- 0.2 mm (P = 0.03). There was a 25% increase in walking time in 8 patients (40%) treated with diuretic versus 1 patient (5%) in the placebo group (P = 0.02). The increases did not depend on changes in blood pressure or heart rate., Conclusion: Therapy with hydrochlorothiazide plus amiloride has potent antianginal effects in patients with stable angina and preserved left ventricular function under treatment with standard antianginal therapy. Because most of the study patients had a history of hypertension the extrapolation of these findings to patients who did not have hypertension requires further investigation.