α1受体阻滞剂多沙唑嗪作为三线抗高血压药物的效用。

Usefulness of the alpha1-blocker doxazosin as a third-line antihypertensive drug.

作者信息

Ohta Yuko, Tsuchihashi Takuya, Onaka Uran, Eto Kimika, Ueno Michio

机构信息

Division of Hypertension, Clinical Research Center, National Kyushu Medical Center, Fukuoka, Japan.

出版信息

Hypertens Res. 2007 Apr;30(4):301-6. doi: 10.1291/hypres.30.301.

DOI:10.1291/hypres.30.301

PMID:17541208

Abstract

It has been reported that a substantial majority of hypertensives receive insufficient blood pressure (BP) control. As combination therapy for the treatment of hypertension, Ca channel blockers (CCBs), angiotensin II (AII) receptor blockers (ARBs), and/or AII-converting enzyme (ACE) inhibitors are mainly prescribed, while the efficacy of alpha(1)-blockers in such combination therapy remains unknown. The aim of this study was to investigate the efficacy of a low dose of an alpha(1)-blocker added to combination therapy with CCBs and either ARBs or ACE inhibitors for the treatment of hypertension. Subjects were 41 hypertensive patients (23 women and 18 men, mean age 66+/-12 years) who had been followed at the National Kyushu Medical Center. All patients showed poor BP control despite haven taken a combination of CCBs and ARBs or ACE inhibitors for more than 3 months. Doxazosin at a dose of 1 to 2 mg was added to each treatment regimen. The changes in various clinical parameters, including BP and blood chemistry, following the addition of doxazosin were then evaluated. The mean follow-up period was 170 days. BP decreased from 152+/-14/81+/-12 mmHg to 135+/-14/70+/-11 mmHg after the addition of doxazosin at a mean dose of 1.5 mg/day (p<0.001). When good systolic blood pressure (SBP) control was defined as <140 mmHg, the prevalence of patients with good SBP control increased from 24% to 61% (p<0.01). Similarly, the prevalence of patients with good diastolic blood pressure (DBP) control (<90 mmHg) increased from 78% to 98% (p<0.01). Patients whose SBP decreased more than 10 mmHg (n=25) showed significantly higher baseline SBP, serum total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared to those who showed less SBP reduction (<10 mmHg) (n=16, p<0.01). Comparable BP reductions were obtained between obese (body mass index [BMI] > or =25, DeltaBP at 3 months: -15+/-15/-12+/-9 mmHg, n=18) and non-obese (BMI<25, DeltaBP: -14+/-19/-7+/-8 mmHg, n=23) patients. The results suggest that addition of a low dose of the alpha(1)-blocker doxazosin effectively reduces BP in patients taking CCBs and ARBs or ACE inhibitors. Thus, doxazosin seems to be useful as a third-line antihypertensive drug.

摘要

据报道，绝大多数高血压患者的血压控制不充分。作为高血压治疗的联合疗法，主要使用钙通道阻滞剂（CCB）、血管紧张素II（AII）受体阻滞剂（ARB）和/或AII转换酶（ACE）抑制剂，而α1阻滞剂在这种联合疗法中的疗效尚不清楚。本研究的目的是探讨在CCB与ARB或ACE抑制剂联合治疗中添加低剂量α1阻滞剂治疗高血压的疗效。研究对象为41例高血压患者（23例女性和18例男性，平均年龄66±12岁），他们一直在九州国立医疗中心接受随访。尽管所有患者联合使用CCB与ARB或ACE抑制剂治疗超过3个月，但血压控制仍不佳。在每个治疗方案中添加剂量为1至2mg的多沙唑嗪。然后评估添加多沙唑嗪后包括血压和血液生化在内的各种临床参数的变化。平均随访期为170天。平均每天添加1.5mg多沙唑嗪后，血压从152±14/81±12mmHg降至135±14/70±11mmHg（p<0.001）。当将良好的收缩压（SBP）控制定义为<140mmHg时，SBP控制良好的患者比例从24%增加到61%（p<0.01）。同样，舒张压（DBP）控制良好（<90mmHg）的患者比例从78%增加到98%（p<0.01）。与SBP降低幅度较小（<10mmHg，n=16）的患者相比，SBP降低幅度超过10mmHg（n=25）的患者基线SBP、血清总胆固醇和低密度脂蛋白（LDL）胆固醇水平显著更高（p<0.01）。肥胖（体重指数[BMI]≥25，3个月时血压变化：-15±15/-12±9mmHg，n=18）和非肥胖（BMI<25，血压变化：-14±19/-7±8mmHg，n=23）患者的血压降低幅度相当。结果表明，在服用CCB与ARB或ACE抑制剂的患者中添加低剂量α1阻滞剂多沙唑嗪可有效降低血压。因此，多沙唑嗪似乎可作为三线抗高血压药物。