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 increased sympathetic drive. The α1-adrenoceptor blocker, doxazosin, increases the coronary vasodilator reserve in patients with syndrome X. To study whether the augmentation is associated with clinical improvement in patients, we conducted a double-blind, placebo controlled, crossover study with doxazosin 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 depression during bicycle exercise testing were compared after treatment with doxazosin 2 mg or placebo for 5 weeks and again after treatment with doxazosin 4 mg or placebo for 10 weeks. Insulin sensitivity was assessed by the minimal model after 10 weeks of doxazosin or placebo treatment. Twelve patients completed the protocol. Doxazosin 4 mg/day decreased systolic blood pressure 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 to 0.1 mV ST-segment depression, and maximal ST-segment depression were similar during treatment with doxazosin and placebo irrespective of the doxazosin dose. Insulin sensitivity was not different with doxazosin and placebo. In conclusion, α1 blockade does not significantly improve exercise duration, angina pectoris, and ST-segment depression despite a favorable vasodilator effect in patients with syndrome X. The absent clinical efficacy of doxazosin may challenge the use of the coronary vasodilator capacity as an appropriate method to subclassify patients with syndrome X.