Tikkanen I, Omvik P, Jensen H A
Department of Medicine, Helsinki University Central Hospital, Finland.
J Hypertens. 1995 Nov;13(11):1343-51. doi: 10.1097/00004872-199511000-00017.
To evaluate the blood pressure lowering efficacy as well as tolerability and safety of the angiotensin II antagonist losartan compared with that of the angiotensin converting enzyme inhibitor enalapril in patients with mild-to-moderate essential hypertension.
The study was a multicentre, double-blind, double-dummy, randomized, parallel study. Patients (n = 407) with diastolic blood pressure > or = 95 and < or = 120 mmHg at the end of a 2-week baseline placebo period were randomly allocated to receive either 50 mg losartan once a day or 20 mg enalapril once a day for 12 weeks. Blood pressure, clinical and laboratory safety, specific symptoms including coughing determined using a symptoms questionnaire and metabolic variables were examined at baseline and at weeks 6 and 12.
Both losartan and enalapril decreased systolic and diastolic blood pressure from baseline at weeks 6 and 12. Blood pressure changes from baseline at trough (22-26 h after the dose) did not differ between the two groups in the per-protocol analysis. Response to treatment at trough was excellent or good (diastolic blood pressure < 90 mmHg or reduction in diastolic blood pressure of 10 mmHg) in 51 and 53% of the patients in the losartan and enalapril groups, respectively. Enalapril administration increased dry coughing symptoms whereas losartan did not. The incidence of dry coughing was 1.0 and 12.2% as a spontaneously reported discomfort at week 12 and 3.0 and 15.1% as a clinical adverse experience in the losartan and enalapril groups, respectively. The difference from baseline at week 12 in the incidence of dry coughing between the two groups was 14.9% as a specific symptom in the symptoms questionnaire. Losartan reduced serum uric acid concentration, whereas effects on other metabolic parameters did not differ between the groups.
Losartan is an effective and well-tolerated antihypertensive drug showing similar blood-pressure-lowering efficacy to that of enalapril at trough. However, in contrast to enalapril, losartan does not increase the incidence of dry coughing. Thus, the angiotensin II antagonist losartan provides a promising new approach to treatment of hypertension.
评估血管紧张素II拮抗剂氯沙坦与血管紧张素转换酶抑制剂依那普利相比，在轻至中度原发性高血压患者中的降压疗效、耐受性及安全性。
本研究为多中心、双盲、双模拟、随机、平行研究。在为期2周的基线安慰剂期结束时，舒张压≥95且≤120 mmHg的患者（n = 407）被随机分配，每天接受50 mg氯沙坦或20 mg依那普利治疗，为期12周。在基线以及第6周和第12周时，检测血压、临床及实验室安全性、使用症状问卷确定的包括咳嗽在内的特定症状以及代谢变量。
氯沙坦和依那普利在第6周和第12周时均使收缩压和舒张压较基线水平降低。在符合方案分析中，两组在谷值（给药后22 - 26小时）时血压较基线的变化无差异。氯沙坦组和依那普利组分别有51%和53%的患者在谷值时对治疗的反应为优或良（舒张压<90 mmHg或舒张压降低10 mmHg）。服用依那普利会增加干咳症状，而氯沙坦则不会。在第12周时，氯沙坦组和依那普利组分别有1.0%和12.2%的患者自发报告干咳不适，作为临床不良事件的发生率分别为3.0%和15.1%。在症状问卷中，两组在第12周时干咳发生率较基线的差异为14.9%。氯沙坦可降低血清尿酸浓度，而两组对其他代谢参数的影响无差异。
氯沙坦是一种有效且耐受性良好的抗高血压药物，在谷值时降压疗效与依那普利相似。然而，与依那普利不同，氯沙坦不会增加干咳的发生率。因此，血管紧张素II拮抗剂氯沙坦为高血压治疗提供了一种有前景的新方法。
