Add-On Effect of Bedtime Dosing of the .ALPHA.1-Adrenergic Receptor Antagonist Doxazosin on Morning Hypertension and Left Ventricular Hypertrophy in Patients Undergoing Long-Term Amlodipine Monotherapy

High morning blood pressure is related to target organ damage and future cardiovascular events. Chronobiologic therapies focusing on the early morning period may be an important strategy for antihypertensive therapy. The aim of this study was to clarify the add-on effects of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning blood pressure in patients with essential hypertension who were under long-acting calcium channel blocker amlodipine monotherapy. The add-on effects of doxazosin at the maximum dose of 6 mg at bedtime on home blood pressure and left ventricular geometry for 1 year were investigated in 49 subjects (37 men and 12 women, aged 57.5+/-9.1 years) with morning hypertension who had been treated with amlodipine alone for more than 1 year. Doxazosin induced a significant decrease in morning blood pressure (145.6+/-5.6/91.5+/-5.4 to 132.4+/-3.7/83.6+/-5.6 mmHg, p<or=0.001/<0.001) without a change of evening blood pressure (128.9+/-5.1/79.8+/-5.1 to 127.7+/-6.0/78.8+/-6.2 mmHg, p=0.056/0.051). Left ventricular mass index (LVMI; 124.8+/-19.8 to 95.6+/-15.7 g/m(2), p<0.001), relative wall thickness (0.457+/-0.061 to 0.405+/-0.047, p<0.001) and homeostasis model assessment of the insulin resistance index (HOMA-IR; 2.62+/-1.43 to 1.33+/-0.75, p<0.001) were decreased after doxazosin therapy. A stepwise multivariate regression analysis revealed that the changes in morning systolic blood pressure (adjusted r(2)=34.9%, p<0.001) and HOMA-IR (adjusted r(2)=4.5%, p=0.046) were significant contributory factors to the change in LVMI after doxazosin therapy. These results suggest that bedtime dosing of doxazosin is useful for the control of morning blood pressure and regression of left ventricular hypertrophy.