Add-On Therapy with a Nighttime Dose of Doxazosin in Patients with Uncontrolled Hypertension: Effects on Autonomic Modulation of the Cardiovascular System

This study was designed to determine whether or not the addition of a single nighttime dose of doxazosin in extended-release form (GITS; gastrointestinal therapeutic system) would affect the autonomic modulation of the cardiovascular system in patients with uncontrolled hypertension treated with a multi-drug regimen. Resting 5-min noninvasive finger blood pressure and ECG signals, as well as 24-h Holter ECGs, were recorded in 30 patients with uncontrolled hypertension on multi-drug treatment before and after 16-week add-on therapy with doxazosin GITS. Cardiovascular autonomic modulation was evaluated by spectral analysis of heart rate variability (HRV) and a cross-correlation method for spontaneous baroreflex sensitivity (BRS) in 5-min resting recordings, and by the analysis of Poincaré plots and phase-rectified signal averaging of the duration of cardiac cycles in 24-h ECG recordings. This combined therapy significantly reduced systolic pressure (19.4+/-3.5 mmHg; p<0.0001), diastolic blood pressure (9.4+/-2.0 mmHg; p=0.0003), and pulse pressure (10.0+/-2.8 mmHg; p=0.0021). Concomitantly, there was a significant increase in resting spontaneous BRS (p=0.0191) and increases in 24-h short-term (p=0.0129) and total (p=0.0153) HRV, but with no significant change in heart rate or other measures of HRV. The improvements in HRV and BRS were observed mainly in patients already treated with thiazide diuretics. There was a significant association (r=0.49; p=0.0065) between the degree of change in diastolic blood pressure and short-term HRV caused by the combined treatment. The addition of 4 mg doxazosin GITS to multi-drug antihypertensive therapy is associated with an improvement in cardiovascular autonomic control.