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

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

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  • 1III Division of Internal Medicine, "L. Sacco" Hospital, Via G.B. Grassi 74, Milan, 20157, Italy, ettore.malacco@tiscali.it.


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.

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