MacKay J H, Arcuri K E, Goldberg A I, Snapinn S M, Sweet C S
Providence Medical Center, Portland, Ore, USA.
Arch Intern Med. 1996 Feb 12;156(3):278-85.
Angiotensin II acts at the cellular level through specific angiotensin II subtype I, AT-1 receptors. Losartan is the first of a new class of antihypertensive agents that specifically block angiotensin II at AT-1 receptors. By acting on complementary and different pharmacologic mechanisms, the concomitant use of low doses of hydrochlorothiazide with losartan may offer an additive antihypertensive activity with fewer adverse experiences.
This double-blind study evaluated losartan concomitantly administered with hydrochlorothiazide as initial therapy in 703 patients with essential hypertension.
The greatest reduction in blood pressure was observed in the 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide group (17.2 mm Hg in sitting systolic blood pressure and 13.2 mm Hg in sitting diastolic blood pressure [P < or = .001]), and the effects of the two components appeared to be additive. Seventy-eight percent of the patients treated with 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide had an excellent or good antihypertensive response (sitting diastolic blood pressure < 90 mm Hg or > or = 90 mm Hg with a reduction of 10 mm Hg or more). Peak (6 hours after dosing) and trough placebo-adjusted ratios for the losartan-hydrochlorothiazide groups ranged from 62% to 85%, indicating that there was a smooth reduction in sitting diastolic blood pressure that was sustained over 24 hours. The most common clinical adverse experiences (> or = 4%) that occurred with an incidence slightly greater than that reported by the placebo-treated patients were headache, asthenia or fatigue, dizziness, sinusitis, and upper respiratory infection.
The concomitant administration of losartan potassium, 50 mg, with 12.5 mg of hydrochlorothiazide once daily produced an additive reduction in trough sitting systolic and diastolic blood pressure and was well tolerated.
血管紧张素II通过特定的血管紧张素II 1型（AT-1）受体在细胞水平发挥作用。氯沙坦是一类新型抗高血压药物中的首个药物，它能在AT-1受体处特异性阻断血管紧张素II。通过作用于互补且不同的药理机制，低剂量氢氯噻嗪与氯沙坦联合使用可能会提供相加的抗高血压活性，且不良反应较少。
这项双盲研究评估了氯沙坦与氢氯噻嗪联合作为703例原发性高血压患者初始治疗的效果。
在氯沙坦钾50毫克和氢氯噻嗪12.5毫克组观察到血压下降幅度最大（坐位收缩压下降17.2毫米汞柱，坐位舒张压下降13.2毫米汞柱[P≤0.001]），且两种成分的作用似乎是相加的。78%接受氯沙坦钾50毫克和氢氯噻嗪12.5毫克治疗的患者有良好或优秀的抗高血压反应（坐位舒张压<90毫米汞柱或≥90毫米汞柱且下降10毫米汞柱或更多）。氯沙坦 - 氢氯噻嗪组的峰（给药后6小时）和谷安慰剂校正比值范围为62%至85%，表明坐位舒张压在24小时内持续平稳下降。最常见的临床不良反应（≥4%），其发生率略高于安慰剂治疗患者报告的发生率，为头痛、乏力或疲劳、头晕、鼻窦炎和上呼吸道感染。
每日一次服用50毫克氯沙坦钾与12.5毫克氢氯噻嗪可使谷坐位收缩压和舒张压相加降低，且耐受性良好。
