比索洛尔/氢氯噻嗪复方片治疗轻中度原发性高血压

Effect of Domestic Produced Bisoprolol Fumarate/Hydrochlorothiazide in Patients with Mild to Moderate Essential Hypertension

目的通过动态血压监测(ABPM)评价国产富马酸比索洛尔/氢氯噻嗪复方片治疗轻中度原发性高血压的降压疗效以及对动脉僵硬度指数(AASI)的影响。方法单中心、开放的临床研究。经过2周的安慰剂导入期,35例轻、中度原发性高血压患者入选。起始口服富马酸比索洛尔2.5mg/氢氯噻嗪6.2mg,1次/d,每次1片;4周后,如诊室坐位舒张压(DBP)≥90mmHg,改为口服富马酸比索洛尔5.0mg/氢氯噻嗪6.2mg,1次/d,每次1片,前后共治疗8周。观察治疗前后动态血压以及AASI的变化。结果符合方案病例数30例;12例在4周时增加剂量。动态血压监测显示,治疗8周后和基线相比:(1)24h平均血压(SBP/DBP)分别下降(12.7±10.1)/(9.2±6.6)mmHg,差异有非常显著意义(P<0.01),降压总有效率为83%,日间和夜间的平均血压均明显降低。(2)SBP和DBP下降的T/P比值分别为84%和92%。(3)AASI显著下降[(0.34±0.14)vs(0.42±0.14),P=0.008],多元逐步回归分析表明AASI的下降主要与脉压差的降低有关。(4)不良事件主要包括血尿酸升高,偶有轻度头晕、头痛。结论(1)国产富马酸比索洛尔/氢氯噻嗪复方片能够有效、平稳地治疗轻、中度原发性高血压,治疗过程中应注意检测尿酸。(2)国产富马酸比索洛尔/氢氯噻嗪复方片显著减低AASI,但该作用产生于降压本身,还是降压药物的类效应尚需进一步研究。

Objective This single-center and open clinical study investigate the effects of domestic produced single pill fixed dose bisoprolol fumarate and hydrochlorothiazide （HCTI） on ambulatory blood pressure （ABP） and ambulatory arterial stiffness index （AASI） in the patients with essential hypertension. Methods After 2 weeks run-in phase, thirty-five patients with mild to moderate hypertension were enrolled to receive bisoprolol fumarate 2. 5 mg/hydrochlorothiazide 6. 2 mg qd for 4 weeks. If the sitting DBP was≥90 mm Hg, the dosage was titrated to 5.0 mg/6.2 mg qd for another 4 weeks. ABP and AASI were investigated before and after the treatment. Results Thirty patients completed the designed protocol. Dosage was titrated in 12 patients to achieve target BP. ABP monitoring at week 8 revealed significant reductions in both 24 h average SBP （12.7±10.1）mm Hg and 24 h average DBP （9.2±6.6）mm Hg （P〈0. 01）. Total response rate was 83% with tough/peak ratio of 84% and 92% for SBP and DBP, respectively. AASI was decreased significantly after 8 weeks treatment [（0. 42±0. 14） vs （0. 34±0. 14 ）, P=0. 008]. Multiple stepwise regression analysis indicated that decreases AASI was independently associated with decreased pulse pressure, serum uric acid significantly after treatment （before：324. 9±71.7 vs after 352. 6±83. 6μmol/L, P〈0.01）. Conclusion Domestic produced Bisoprolol/ HCTZ is effective in the treatment of patients with mild moderate hypertension and reduce AASI significantly. Further study is advocated whether decreased AASI is simply the result of lowered BP or the result of class effect of 18-blocker/diuretics combination.