Clinical efficacy and tolerability of alpha-blocker doxazosin as add-on therapy in patients with hypertension and impaired glucose metabolism

Abstract Background and aim The aim of this trial was to evaluate the effect of doxazosin as add-on therapy in patients with hypertension not adequately controlled on current antihypertensive therapy, and impaired glucose metabolism. The effect of doxazosin administered as add-on therapy was to be considered significant both from clinical and statistical viewpoints if the proportion of patients with adequate control of blood pressure (BP Method and results It was an open, multicenter phase IV study, lasting 19 weeks: 3-week qualifying/placebo run-in period+16-week dose titration/add on therapy period, involving 264 out-patients (158 m and 106 f; mean age±SD: 60.9±8.6 years; mean BMI±SD: basal 29.5±5.1, final 30.2±4.6) with blood pressure still >130/85 mmHg in spite of the antihypertensive treatment (ACE inhibitors 44%, AT II antagonists 21%, Ca antagonists 12%, other drugs 8%, polytherapy 15%) and affected by type 2 diabetes ( n =219), impaired fasting glucose (IFG; n =16) or impaired glucose tolerance (IGT; n =29). Following a run-in, 3-week qualifying phase during which placebo was added to ongoing antihypertensive treatment, 16-week treatment with doxazosin was added at dosages from 1 up to 8 mg/day. Main outcome measures were: the percentage of patients with blood pressure Results 35% of patients were responsive (BP P P P P P P Six patients (2.3%) reported 8 adverse drug reactions: dizziness (3), edema (2), headache (2), asthenia (1). In one out of these 6 patients, in whom doxazosin was associated to the ACE inhibitor quinapril, adverse reaction (peripheral edema) led to treatment withdrawal. Conclusion In patients not responsive to antihypertensive treatment and concomitantly affected by impaired glucose metabolism, achievement of target BP was obtained in more than one third of cases after 16-week add-on treatment with doxazosin. Changes in glyco-lipidic parameters and reduction of 10-year CHD risk observed during the study, although of moderate extent, confirm the overall favourable effect of antihypertensive combinations including doxazosin.