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奈必洛尔/氢氯噻嗪:一种用于有效简化抗高血压治疗的新型固定剂量复方制剂。

Nebivolol/Hydrochlorothiazide : a new fixed-dose combination for effective simplified antihypertensive therapy.

作者信息

Malacco Ettore

机构信息

III Division of Internal Medicine, "L. Sacco" Hospital, Via G.B. Grassi 74, Milan, 20157, Italy,

出版信息

High Blood Press Cardiovasc Prev. 2008 Apr;15(2):75-84. doi: 10.2165/00151642-200815020-00006. Epub 2013 Jan 3.

Abstract

Hypertension is a major independent risk factor for cardiovascular (CV) morbidity and mortality and is combined with additional CV risk factors, such as diabetes mellitus, dyslipidaemia, heart disease, metabolic syndrome, smoking and obesity in many hypertensive individuals. The prevention of CV disease with antihypertensive therapy has been widely demonstrated, with a 30-40% reduction in stroke and a 20% reduction in coronary events in patients receiving antihypertensive drugs compared with untreated hypertensive individuals. Even small decreases in blood pressure (BP) correlate with a significantly lower incidence of CV events; this is independent of drug class used, but dependent on the extent of BP reduction achieved. All antihypertensive drugs lower BP to a similar extent and are suitable for long-term therapy. Treatment guidelines recommend that antihypertensive treatment should be initiated early to reach a target BP value of ≤140/90 mmHg, or lower in high-risk patients, in order to maximize the long-term benefits in CV mortality and morbidity reduction. However, the proportion of patients responding to monotherapy is generally low; therefore, first-line therapy with a combination of antihypertensive drugs is recommended in non-responders and those with multiple risk factors or subclinical organ damage. The combination of β-blocker/thiazide diuretic is frequently used in clinical practice and as reference treatment in clinical trials. Nebivolol, a third-generation cardioselective vasodilatory β-blocker, shows an additive effect in reducing systolic and diastolic BP when combined with hydrochlorothiazide (HCTZ). In monotherapy non-responders, the combination improves response and BP normalization rates compared with monotherapy. Since pharmacokinetic studies have shown that fixed-dose nebivolol-HCTZ therapy is bioequivalent to the two agents administered concomitantly, this combination is useful in monotherapy non-responders and for those who require rapid BP control to prevent end-organ damage. In addition, a simplified regimen improves patient compliance - a major obstacle to achieving target BP levels. In addition to providing enhanced BP reduction and control, nebivolol-HCTZ is well tolerated, with a similar incidence of adverse events to that observed with either monotherapy, and a neutral impact on lipid and glucose metabolism.

摘要

高血压是心血管(CV)发病和死亡的主要独立危险因素,在许多高血压患者中还伴有其他CV危险因素,如糖尿病、血脂异常、心脏病、代谢综合征、吸烟和肥胖。抗高血压治疗预防CV疾病已得到广泛证实,与未治疗的高血压患者相比,接受抗高血压药物治疗的患者中风减少30%-40%,冠状动脉事件减少20%。即使血压(BP)小幅下降也与CV事件发生率显著降低相关;这与所用药物类别无关,但取决于实现的BP降低程度。所有抗高血压药物降低BP的程度相似,适用于长期治疗。治疗指南建议应尽早开始抗高血压治疗,以使目标BP值≤140/90 mmHg,高危患者的目标值更低,以便在降低CV死亡率和发病率方面最大化长期益处。然而,对单一疗法有反应的患者比例通常较低;因此,对于无反应者以及有多种危险因素或亚临床器官损害的患者,建议采用联合抗高血压药物进行一线治疗。β受体阻滞剂/噻嗪类利尿剂联合用药在临床实践中经常使用,并且在临床试验中作为对照治疗。奈必洛尔是一种第三代心脏选择性血管舒张β受体阻滞剂,与氢氯噻嗪(HCTZ)联合使用时,在降低收缩压和舒张压方面显示出相加作用。在单一疗法无反应者中,与单一疗法相比,联合用药可提高反应率和BP正常化率。由于药代动力学研究表明,固定剂量的奈必洛尔-HCTZ疗法与同时服用两种药物具有生物等效性,这种联合用药对单一疗法无反应者以及需要快速控制BP以预防终末器官损害的患者有用。此外,简化的治疗方案可提高患者依从性——这是实现目标BP水平的主要障碍。除了增强BP降低和控制效果外,奈必洛尔-HCTZ耐受性良好,不良事件发生率与单一疗法相似,并且对脂质和葡萄糖代谢无影响。

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