Comparison of Different Alpha-blocker Combinations in Male Hypertensives with Refractory Lower Urinary Tract Symptoms

Keon Cheol Lee; Jong Gu Kim; Sung Yong Cho; Joon Sung Jeon; In Rae Cho

doi:10.5534/kja.2011.29.3.242

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Lee, Kim, Cho, Jeon, and Cho: Comparison of Different Alpha-blocker Combinations in Male Hypertensives with Refractory Lower Urinary Tract Symptoms

Original Article

Korean J Androl 2011;29(3):242-250.

Published online: 22 December 2011

DOI: https://doi.org/10.5534/kja.2011.29.3.242

Comparison of Different Alpha-blocker Combinations in Male Hypertensives with Refractory Lower Urinary Tract Symptoms

Keon Cheol Lee¹, Jong Gu Kim², Sung Yong Cho¹, Joon Sung Jeon¹, In Rae Cho¹

¹Department of Urology, Inje University Ilsanpaik Hospital, Goyang, Korea

²Happy Urology Clinic, Ansan, Korea

Correspondence to: In Rae Cho Department of Urology, Inje University Ilsanpaik Hospital, 2240, Daehwa-dong, Ilsanseo-gu, Goyang 411-706, Korea Tel: 031-910-7230, Fax: 031-910-7239 E-mail: ircho@paik.ac.kr

Received 8 December 201114 December 2011 Accepted 14 December 2011

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

We compared the efficacy and safety profiles of dose increase, traditional combination methods, and combining different alpha blockers in hypertensive males with lower urinary tract symptom (LUTS) refractory to an initial dose of 4 mg doxazosin.

Materials and Methods

Between 2000 and 2005, 374 male patients with LUTS and hypertension unresponsive to 4 weeks of 4 mg doxazosin were enrolled. The subjects were randomly classified into 3 groups, 8 mg/day of doxazosin (D group), 4 mg of doxazosin plus 0.2 mg/day of tamsulosin (DT group), and 4 mg doxazosin plus 5 mg/day finasteride (DF group). Patients were evaluated based on their International Prostate Symptom Score (IPSS), quality of life (QOL), uroflowmetry and blood pressure (BP) and adverse events (AEs) at the baseline and 3 and 12 months after treatment.

Results

The 269 patients (71.9%) were followed for at least 1 year (D group n=84, DT group n=115, and DF group n=70). The clinical parameters before and after initial 4 mg/day doxazosin were not different among the 3 groups. IPSS improvement after 3 months and maximal flow rate (Qmax) improvement after 3 and 12 months were significantly higher in the D and DT groups than the DF group (p＜0.05). Sitting systolic and diastolic BP of the D group decreased larger than those of the other 2 groups (p＜0.05). At least one of the AEs was reported by 29.0%, 19.3%, and 17.3% of patients in the D, DT, and DF groups, respectively. In particular, vasodilatory AEs of the D group (28.2%) were higher than those of other groups (p＜0.05), and sexual function AEs of the DF group (10.9%) were higher than those of other groups (p＜0.05).

Conclusions

Doxazosin 4 mg plus tamsulosin 0.2 mg has comparable efficacy but less vasodilatory AEs than doxazosin 8 mg, and has superior efficacy to but comparable vasodilatory AEs to 4 mg doxazosin plus 5 mg finasteride in hypertensive male LUTS patients.

Keywords: Urinary tract, Symptoms, Doxazosin, Tamsulosin, Finasteride

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Fig. 1.

Changes in systolic and diastolic blood pressure after 3 and 12 months of dose increase or combination therapy in the 3 groups. The 8 mg doxazosin group after 3 and 12 months of treatment shows a significantly larger BP change than the other groups. SBP: systolic blood pressure, DBP: diastolic blood pressure. ∗Means p＜0.05 compared with the other groups. Independent T-test.

Table 1.

Baseline demographics and characteristics show no difference among groups (mean±SD)

	Doxazosin (8 mg) (n=124, Group D)	Doxazosin (4 mg)＋Tamsulosin (0.2 mg) (n=140, Group DT)	Doxazosin (4 mg)＋Finasteride (5 mg) (n=110, Group DF)
Age (years)	66.9±11.1	66.4±9.4	67.0±8.3
IPSS	21.8±7.4	21.5±7.5	20.8±7.6
QOL	3.8±0.9	3.6±0.8	3.6±0.8
Qmax (ml/s)	11.5±4.5	11.1±4.7	11.2±4.4
PVR (ml)	30.2±42.3	31.9±38.3	29.1±37.5
PSA (ng/ml)	2.47±4.64	2.48±4.48	2.53±4.97

One-way ANOVA. IPSS: international prostate symptom score, QOL: quality of life, Qmax: maximal flow rate, PVR: post-void residual urine, PSA: prostate-specific antigen. p＞0.05 for all parameters.

Table 2.

Compared with before-treatment, each group showed improvement of all parameters at 3 and 12 months after the dose increase or beginning of combination therapy (mean±SD)

	Doxazosin (8 mg) (n=84, Group D)	Doxazosin (4 mg)＋Tamsulosin (0.2 mg) (n=115, Group DT)	Doxazosin (4 mg)＋Finasteride (5 mg) (n=70, Group DF)
IPSS
Before	20.9±7.5	20.6±7.2	19.8±7.8
3 Mo	13.9±7.9∗	13.5±6.1∗	15.5±7.3∗
12 Mo	14.1±8.4∗	13.5±6.2∗	13.8±7.4∗
QOL
Before	3.6±0.9	3.5±0.8	3.4±0.8
3 Mo	2.8±0.9∗	2.7±0.7∗	2.8±0.9∗
12 Mo	2.9±1.0∗	2.7±0.7∗	2.7±0.9∗
Qmax (ml/s)
Before	12.2±4.9	11.4±4.6	11.8±4.5
3 Mo	16.5±5.6∗	16.7±5.2∗	13.5±5.8∗
12 Mo	16.7±7.1∗	16.3±5.3∗	13.9±4.8∗

Paired T-test. IPSS: International Prostate Symptom Score, Mo: month, QOL: quality of life, Qmax: maximal flow rate. ∗p＜0.05 compared with before-treatment.

Table 3.

Compared among groups, the DF group shows less improvement in 3-month IPSS and Qmax and 12-month Qmax parameters (mean±SD)

	Doxazosin (8 mg) (n=84, Group D)	Doxazosin (4 mg)＋Tamsulosin (0.2 mg) (n=115, Group DT)	Doxazosin (4 mg)＋Finasteride (5 mg) (n=70, Group DF)
Δ IPSS
3 Mo	−7.0±6.0^a	−7.1±5.9^b	−4.3±7.0^c
12 Mo	−6.8±6.2	−7.0±6.1	−5.9±7.7
Δ QOL
3 Mo	−0.8±1.0	−0.8±0.9	−0.6±0.9
12 Mo	−0.6±1.0	−0.8±0.9	−0.7±0.9
Δ Qmax (ml/s)
3 Mo	4.3±4.0^d	5.2±3.4^e	1.7±4.2^f
12 Mo	4.4±5.4^g	4.9±3.5^h	2.1±4.4ⁱ

Independent T-test. Δ: change, DF: doxazosin (4 mg) plus finasteride (5 mg), IPSS: International Prostate Symptom Score, Mo: month, QOL: quality of life, Qmax: maximal flow rate. a vs c: p=0.032, b vs c: p=0.002. d vs f: p=0.000, e vs f: p=0.000, g vs i: p=0.026, h vs i: p=0.001.

Table 4.

The incidence of adverse events in all 374 patients enrolled, expressed as number (percentage)

	Doxazosin (8 mg) (n=124, Group D)	Doxazosin (4 mg)＋ Tamsulosin (0.2 mg) (n=140, Group DT)	Doxazosin (4 mg)＋ Finasteride (5 mg) (n=110, Group DF)
Vasodilatory AEs	35 (28.2)^∗,†	20 (14.3)^∗	12 (10.9)^†
Dizziness	14 (11.3)	9 (6.4)	5 (4.5)
Postural hypotension	5 (4.0)	4 (2.9)	2 (1.8)
Palpitation	3 (2.4)	1 (0.7)	0 (0)
Headache	7 (5.6)	2 (1.4)	2 (1.8)
Edema	3 (2.4)	2 (1.4)	2 (1.8)
Fatigue	1 (0.8)	1 (0.7)	1 (0.9)
Syncope	2 (1.6)	1 (0.7)	0 (0)
Sexual function AEs	4 (3.2)^‡	8 (5.7)^§	12 (10.9)^†,§
Impotence	1 (0.8)	1 (0.7)	1 (0.9)
Decreased libido	1 (0.8)	1 (0.7)	5 (4.5)
Ejaculatory disorder	2 (1.6)	6 (4.3)	6 (5.5)
Gynecomastia	0 (0)	0 (0)	0 (0)
Other AEs	4 (3.2)	3 (2.1)	2 (1.8)
Urticaria	0 (0.0)	1 (0.7)	1 (0.9)
Nasal stuffiness	2 (1.6)	1 (0.7)	1 (0.9)
Muscle spasms	2 (1.6)	0 (0)	0 (0)
GI trouble	0 (0)	1 (0.7)	0 (0)
Any AEs	43 (34.6)^∥,¶	31 (22.1)^∥	26 (23.6)^¶

Independent T-test. AEs: adverse events, Some patients can have more than one AE.

^∗ ,†,‡,§,∥,¶p＜0.05 compared with other groups.

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