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厄贝沙坦与氢氯噻嗪联合治疗高血压

Irbesartan and hydrochlorothiazide association in the treatment of hypertension.

作者信息

Derosa Giuseppe, Ferrari Ilaria, Cicero Arrigo F G

机构信息

Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

出版信息

Curr Vasc Pharmacol. 2009 Apr;7(2):120-36. doi: 10.2174/157016109787455644.

Abstract

Blood pressure (BP) is one of the most important and common vascular risk factors but it is often poorly controlled. Inhibition of the renin-angiotensin-aldosterone system (RAAS) provides beneficial effects in hypertensives. The association of low-dosed diuretics in combination with RAAS blocking agents allows maximum benefit from potassium depletion and control of compensatory increase in renin secretion, so increasing the efficacy and safety of RAAS blockers. Irbesartan is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with type 2 diabetes mellitus and nephropathy. Once-daily irbesartan administration provides 24h control of BP. In patients with mild-to-moderate hypertension, irbesartan was as effective as enalapril, atenolol and amlodipine, and more effective than losartan and valsartan in terms of absolute reduction in BP and response rate. Irbesartan also induced regression of left ventricular hypertrophy. Moreover, irbesartan 300 mg/day exerts a significant renoprotective effect in hypertensive type 2 diabetic patients. The relative risk of doubling of serum creatinine was significantly lower with irbesartan than amlodipine or placebo. Irbesartan was also effective in non-diabetic nephropatic patients. Moreover, irbesartan has peroxisome proliferator-activated receptor agonistic effects in in vitro studies, and it also demonstrated beneficial effects on inflammatory markers of atherosclerosis and endothelial function. The overall incidence of adverse events is similar to that of placebo. A fixed dose of hydrochlorothiazide (HCTZ) and irbesartan shows additive antihypertensive effect in a dose dependent manner up to HCTZ 25 mg and irbesartan 300 mg with high tolerability in diverse patient groups. Combination effects on end organ protection must be evaluated by broad spectrum studies. Ongoing trials about irbesartan and its combination with diuretics may provide necessary data to interpret the value of this association among others.

摘要

血压(BP)是最重要且常见的血管危险因素之一,但往往控制不佳。抑制肾素-血管紧张素-醛固酮系统(RAAS)对高血压患者有益。低剂量利尿剂与RAAS阻断剂联合使用,可最大程度地受益于钾耗竭,并控制肾素分泌的代偿性增加,从而提高RAAS阻滞剂的疗效和安全性。厄贝沙坦是一种强效且选择性的血管紧张素II 1型受体拮抗剂,适用于高血压患者,包括2型糖尿病和肾病患者。每日一次服用厄贝沙坦可实现24小时血压控制。在轻度至中度高血压患者中,厄贝沙坦在降低血压绝对值和有效率方面与依那普利、阿替洛尔和氨氯地平效果相当,且比氯沙坦和缬沙坦更有效。厄贝沙坦还可使左心室肥厚消退。此外,厄贝沙坦300毫克/天对2型糖尿病高血压患者具有显著的肾脏保护作用。与氨氯地平或安慰剂相比,厄贝沙坦使血清肌酐翻倍的相对风险显著更低。厄贝沙坦对非糖尿病肾病患者也有效。此外,在体外研究中,厄贝沙坦具有过氧化物酶体增殖物激活受体激动作用,还对动脉粥样硬化的炎症标志物和内皮功能显示出有益作用。不良事件的总体发生率与安慰剂相似。固定剂量的氢氯噻嗪(HCTZ)和厄贝沙坦在高达HCTZ 25毫克和厄贝沙坦300毫克时呈剂量依赖性的相加降压作用,在不同患者群体中耐受性良好。对终末器官保护的联合作用必须通过广泛的研究进行评估。正在进行的关于厄贝沙坦及其与利尿剂联合使用的试验可能会提供必要数据,以阐释这种联合用药等方面的价值。

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