替米沙坦联用氢氯噻嗪治疗轻中度高血压的临床研究

Efficacy and safety of telmisartan in combination with hydrochlo-rothiazide in patients with mild to moderate hypertension

目的:评估国产替米沙坦片联用氢氯噻嗪片治疗轻中度高血压的有效性和安全性。方法:152例轻中度原发性高血压患者经2周安慰剂洗脱期后,用替米沙坦40mg治疗4周,4周末单剂治疗无效的72例患者接受替米沙坦40mg和氢氯噻嗪12．5mg治疗8周。在洗脱期末(0周)、替米沙坦单剂治疗末(4周末)和替米沙坦联用氢氯噻嗪8周末(12周末),进行诊室血压(CBP)、心电图、血生化指标、24h动态血压监测(ABPM)、脉搏波传导速度(PWV)和超声心动图检测。结果:12周末与4周末比较,诊室收缩压(CSBP)和诊室舒张压(CDBP)均显著降低(P＜0．001),降压幅度达16．70/15．28mmHg,总有效率91．67%,不良事件发生率9．7%;24h平均收缩压和舒张压均显著降低(P＜0．001),降幅为8．41/6．21mmHg,24h平均脉压(PP)也显著降低,降幅为4．60 mmHg,白昼及夜间血压及血压负荷值均显著降低(P＜0．05),12周末收缩压谷峰比为72．66%,舒张压谷峰比为76．21%。4周末, PWV显著降低[(11．17±1．83)vs(10．19±1．44)m·s^(-1),P＜0．05],舒张早期血流峰值流速(E峰)与舒张晚期血流峰值流速(A峰)的比值(E/A)显著增加、左室等容舒张时间(IVRT)显著缩短,左室重量指数(LVMI)也显著改善(P＜0．05)。12周末,PWV进一步降低至(9．24±1．01)m·s^(-1)(P＜0．001),舒张功能显著改善(P＜0,01), LVMI也显著降低(P＜0．001)。结论:国产替米沙坦片40mg联用氢氯噻嗪片12．5mg对于替米沙坦40mg单剂治疗4周无效的轻中度高血压患者安全有效。

Objective： To evaluate the efficacy and safety of adjunctive therapy of telmisartan with hydrochlorothiazide in patients with mild to moderate hypertension. Methods：After 2-week wash-out period, 152 patients with mild to moderate essential hypertension were administered with telmisartan 40 mg alone for 4 weeks. At the end of the 4-week therapy, patients who had diastolic blood pressure 〉 90 mmHg were treated with the combination of telmisartan 40 mg with hydrochlorothiazide 12.5 mg for additional 8 weeks. The efficacy was evaluated by the clinic blood pressure （CBP）, electrocardiogram （ECG）, blood biochemical parameters, 24 h-ambulatory blood pressure（ABPM）, pulse wave velocity （PWV） and two-dimensional eehoeardiography at the end of0W, 4W and 12W. Results：Compared with the telmisartan alone, the patients with the combination therapy（91.67% ）experienced significant reductions of clinical systolic blood pressure （CSBP） and clinical diastolic blood pressure （CDBP） （ P 〈 0. 001 ） , decreasing by 16.70/15.28 mmHg. The patients showed significant reductions of 24 h mean SBP and DBP by 8.41/6.21 mmHg, and 24 h pulse pressure （24 hPP） by 4.60 mmHg. The daytime, nighttime blood pressure and blood pressure load were all decreased markedly（ P 〈0.05 ）. The SBP and DBP trough/peak ratio （T/P） was 72.66% vs. 76.21% at the end of the 12W. At the end of 4W, the patients had the PWV decrease of（10. 19±1.44）from（11. 17±1.83）m·s ^-1（P〈0.05）at the end of 4W and of（9.24±1.01）m·s^-1（P〈0.01） at the end of 12W. In addition, the patients significantly showed the increase of E/A ratio, the shortness of isovolumie relaxation time（IVRT） , and reduction of left ventrieular mass index（LVMI） （P 〈0.05） at the end of 4W, and further improvements of diastolic function and LVMI at the end of 12W（P 〈0.01 ）. The incidence of adverse events was 9.7%. Conclusions： Combination of telmisartan 40 mg with hydrochlorothlazide tablets 12.5 mg offered therapeutic options in patients with mild to moderate hypertension who were non-responsive to telmisartan monotherapy.