Effects of doxazosin on exercise-induced angina pectoris, ST-segment depression, and insulin sensitivity in patients with syndrome X

A significant proportion of patients with cardiac syndrome X have impaired coronary vasodilator capacity, which is thought to be caused by an increase d sympathetic drive. The alpha(1)-adrenoceptor blocker, doxazosin, increase s the coronary vasodilator reserve in patients with syndrome X. To study wh ether the augmentation is associated with clinical improvement in patients, we conducted a double-blind, placebo controlled, crossover study with doxa zosin 1 to 4 mg once daily for 10 weeks in 16 patients with syndrome X (14 women and 2 men; mean +/- SD age 56 +/- 5 years). Time to angina, exercise duration, time to 0.1 mV ST-segment depression, and maximal ST-segment depr ession during bicycle exercise testing were compared after treatment with d oxazosin 2 mg or placebo for 5 weeks and again after treatment with doxazos in 4 mg or placebo for 10 weeks. Insulin sensitivity was assessed by the mi nimal model after 10 weeks of doxazosin or placebo treatment. Twelve patien ts completed the protocol. Doxazosin 4 mg/day decreased systolic blood pres sure at rest (109 +/- 16 vs 125 +/- 18 mm Hg, p <0.05) and increased basal heart rate (85 +/- 9 vs 76 +/- 11 beats/min, p <0.05), whereas hemodynamics were unaffected during exercise. Time to angina, exercise duration, time t o 0.1 mV ST-segment depression, and maximal ST-segment depression were simi lar during treatment with doxazosin and placebo irrespective of the doxazos in dose. Insulin sensitivity was not different with doxazosin and placebo. In conclusion, CY, blockade does not significantly improve exercise duratio n, angina pectoris, and ST-segment depression despite a favorable vasodilat or effect in patients with syndrome X. The absent clinical efficacy of doxa zosin may challenge the use of the coronary vasodilator capacity as an appr opriate method to subclassify patients with syndrome X. (C) 1998 by Excerpt a Medica, Inc.