Reams G P, Bauer J H
Drugs. 1985;30 Suppl 1:59-69. doi: 10.2165/00003495-198500301-00009.
18 renovascular hypertensive patients were entered into a randomised, double-blind protocol to assess the safety and efficacy of enalapril (5 to 20 mg twice-daily) and hydrochlorothiazide (50 to 100 mg/day), versus triple-drug therapy employing hydrochlorothiazide (50 to 100 mg/day), timolol (10 to 30 mg twice-daily) and hydralazine (50 to 150 mg twice-daily). Specifically monitored were the effects of each drug regimen on blood pressure, plasma renin activity and angiotensin II, glomerular filtration rate by insulin clearance, and effective renal plasma flow by para-aminohippurate clearance. Results indicate that enalapril/hydrochlorothiazide was more effective than triple-drug therapy in lowering blood pressure. All patients on enalapril/hydrochlorothiazide had excellent control of blood pressure, and there were no adverse effects. In contrast, 50% of the patients on triple-drug therapy had either uncontrolled blood pressure or significant drug-related side effects. Patients who were uncontrolled or intolerant of triple-drug therapy were well controlled on enalapril/hydrochlorothiazide. Patients on enalapril/hydrochlorothiazide demonstrated stimulation of plasma renin activity with inhibition of plasma angiotensin II, indicating adherence with therapy. Therapy for both unilateral and bilateral renovascular hypertension with enalapril/hydrochlorothiazide did not result in reductions in either glomerular filtration rate or effective renal plasma flow, except in 1 patient with a functional solitary stenotic kidney. In contrast, triple-drug therapy was generally associated with modest reductions in glomerular filtration rate and effective renal plasma flow, with a severe reduction in glomerular filtration rate and effective renal plasma flow occurring in 1 patient with bilateral symmetrical renovascular disease. We conclude that the combination of enalapril and hydrochlorothiazide is a safer and more effective regimen, compared with triple-drug therapy, for the treatment of renovascular hypertension.
18例肾血管性高血压患者进入一项随机双盲试验方案，以评估依那普利（每日两次，每次5至20毫克）和氢氯噻嗪（每日50至100毫克）联合用药，与采用氢氯噻嗪（每日50至100毫克）、噻吗洛尔（每日两次，每次10至30毫克）和肼屈嗪（每日两次，每次50至150毫克）的三联药物疗法相比的安全性和有效性。具体监测了每种药物疗法对血压、血浆肾素活性和血管紧张素II、通过胰岛素清除率测定的肾小球滤过率以及通过对氨基马尿酸清除率测定的有效肾血浆流量的影响。结果表明，依那普利/氢氯噻嗪在降低血压方面比三联药物疗法更有效。所有接受依那普利/氢氯噻嗪治疗的患者血压控制良好，且无不良反应。相比之下，接受三联药物疗法的患者中有50%血压控制不佳或出现明显的药物相关副作用。对三联药物疗法控制不佳或不耐受的患者在接受依那普利/氢氯噻嗪治疗后血压得到良好控制。接受依那普利/氢氯噻嗪治疗的患者血浆肾素活性升高，血浆血管紧张素II受到抑制，表明依从治疗。除1例功能性孤立狭窄肾患者外，依那普利/氢氯噻嗪治疗单侧和双侧肾血管性高血压均未导致肾小球滤过率或有效肾血浆流量降低。相比之下，三联药物疗法通常与肾小球滤过率和有效肾血浆流量适度降低有关，1例双侧对称性肾血管疾病患者出现肾小球滤过率和有效肾血浆流量严重降低。我们得出结论，与三联药物疗法相比，依那普利和氢氯噻嗪联合用药是治疗肾血管性高血压更安全、更有效的方案。
