Long‐term (4 year) efficacy and tolerability of doxazosin for the treatment of concurrent benign prostatic hyperplasia and hypertension

Abstract

Background: The a 1 -adrenoceptor antagonist doxazosin has proved successful in treating patients with concurrent benign prostatic hyperplasia (BPH) and hypertension in short-term studies. However, both conditions are chronic and may worsen over time. The aim of this study was, therefore, to examine the tolerability and efficacy of doxazosin in the long-term treatment of concurrent BPH and hypertension. Methods: This study was a longitudinal extension of earlier double-blind trials. Patients were enrolled into the study on a rolling basis. From a total of 178 BPH patients with hypertension enrolled into the study, 28 had reached 48 months of open-label treatment with doxazosin at the time of the final data cutoff. Results: Treatment with doxazosin resulted in sustained benefits for BPH patients over the whole study period, with significant improvements in the severity (12.2%, P < 0.001) and bothersomeness (13.2%, P < 0.001) of BPH symptoms, and in the maximum urinary flow rate (26.6%, P < 0.05) from baseline to the end of the 4-year period. There was also a significant and sustained reduction in diastolic blood pressure. The efficacy of doxazosin treatment for both BPH and hypertension was maintained over the 4-year period, despite the tendency of these conditions to worsen with time. Comparison of adverse events in patients with long-and short-term hypertension and BPH demonstrates that the safety of doxazosin is not altered during long-term therapy.Conclusions: This study demonstrates that doxazosin appears to be well tolerated and efficacious in the long-term management of concurrent BPH and hypertension.

Tolerability of -Blockade With Doxazosin as a Therapeutic Option for Symptomatic Benign Prostatic Hyperplasia in the Elderly Patient: A Pooled Analysis of Seven Double-Blind, Placebo-Controlled Studies

“…Ongoing studies with doxazosin have demonstrated good tolerability for follow-up periods currently extending to as much as 4 years (23,(31)(32)(33). The half-life of doxazosin permits once-daily dosing, and this is an important consideration for elderly patients where compliance is concerned.…”

Clinical ease of using doxazosin in BPH patients with and without hypertension

“…29 This study demonstrated that the efficacy of doxazosin treatment for both BPH and diastolic hypertension was maintained with 4 y of continuous treatment. Analysis of data for 16 patients who completed 4 y of open-label doxazosin treatment showed significant mean reductions in sitting and standing DBP of 7.8 and 9.3 mmHg, respectively (Po0.001 for both reductions) from mean baseline values of 97.0 and 99.4 mmHg, respectively.…”

“…The discontinuation rates in the 'treated/well controlled' and Ease of using doxazosin in BPH WD Steers and RS Kirby 'untreated/normotensive' groups were 6.3 and 5.6%, respectively, compared with rates of 11.3% and 8.1% in the 'treated/poorly controlled' and 'untreated/hypertensive' groups, respectively. A double-blind, placebo-controlled, dose-response study 28 and a long-term, open-label extension of this study 29 demonstrated a significant blood pressure-lowering effect of doxazosin therapy in patients with BPH and concomitant hypertension. In the multicenter, double-blind, placebo-controlled, dose-response study, 248 patients (aged X45 y) with symptomatic BPH and mild-to-moderate hypertension (baseline sitting DBP of 90-114 mmHg) were randomized to doxazosin 2 mg (n ¼ 39), 4 mg (n ¼ 46), 8 mg (n ¼ 45), or 12 mg (n ¼ 45) or placebo (n ¼ 41) for a 14-week period, following a 2-week placebo run-in period.…”

Molecular classification of doxazosin-induced alterations in the rat prostate using gene expression profiling

“…Although the clinical efficacy of a 1 -adrenoceptor (AR) antagonists for the treatment of benign prostatic hyperplasia (BPH) is not disputed (Kirby and Pool, 1997;Fawzy et al, 1999;Dunn et al, 2002), their ability to maintain long-term effectiveness has only been recently investigated (Andersson et al, 2002;Bautista et al, 2003;McConnell et al, 2003). In 1994, Bendix Holme and associates, in an original clinical study on the long-term effects of doxazosin, reported that overall improvement of BPH symptoms diminished significantly over time.…”