Arterial hypertension is one of the major diseases in the Western

Arterial hypertension is one of the major diseases in the Western world. successfully because it can block the diuretic-induced increase in plasma renin activity. Its combination with hydrochlorothiazide in a single pill has been investigated and shown to be superior to monotherapy with respect to blood pressure control and improvement in patient compliance with therapy. Further studies are needed to show whether aliskiren and its combination with hydrochlorothiazide is effective in preventing cardiovascular events and mortality when end organ damage is present. Keywords: aliskiren hydrochlorothiazide combination hypertension Introduction Arterial hypertension is one of the most common diseases in the developed world. It is one of the major cardiovascular risk factors for development of coronary heart disease heart failure stroke and chronic kidney disease. In 2000 more than 970 million people worldwide had elevated blood pressure and this number is expected to have increased by 60% in 2025.1 According to the World Health Organization arterial hypertension accounts for 7. 1 million deaths per year and this number is expected to rise in the future.2 The guidelines of the 7th Joint National Committee on Prevention Detection Evaluation and Treatment of High Blood Pressure (JNC 7) as well as those of the European Society of Cardiology and European Society of Hypertension recommend a target blood pressure lower than 140/90 mmHg in uncomplicated hypertension and lower than 130/80 mmHg when additional risk factors such as diabetes or coronary heart disease are present.3 4 Despite these recommendations and the existence of many different antihypertensive drugs hypertension in the US is only controlled in about 30%-60% of patients and this rate is much lower in western European countries.5 6 At least 75% of hypertensive patients require combination therapy to achieve current DPC-423 blood pressure goals.7-9 Combination of several agents allows for synergistic action and use of lower doses of the individual drugs leading to a reduction in side effects and improvement of patient compliance.10 Therefore combination treatment as first-line therapy is a logical choice for patients with moderate to severe hypertension. The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in the pathophysiology of hypertension and cardiovascular diseases.11 Drugs that target the RAAS such as angiotensin-converting enzyme (ACE) inhibitors and blockers of angiotensin receptor-1 (ARBs) are effective in reducing blood pressure as well as the DPC-423 morbidity and mortality associated with hypertension and cardiovascular diseases. Their low rate of side effects makes them well tolerated and therefore attractive as first-line agents in the treatment of arterial hypertension.12 Blockers of the RAAS are widely combined with thiazide diuretics mainly hydrochlorothiazide a strategy supported pathophysiologically by the mechanism of action of the two drug classes. Hydrochlorothiazide leads to activation of the RAAS through sodium and water depletion which limits its antihypertensive effects (Table 1) and its combination with a RAAS blocker potentiates the effects of both agents.13 Table 1 Effects of RAAS blockers and common antihypertensive agents on different RAAS components A recent addition to the family of Mouse monoclonal to ICAM1 RAAS-blockers is aliskiren a direct renin inhibitor now approved for the treatment of hypertension. Several studies have already investigated the effects of aliskiren as monotherapy in lowering blood pressure and in combination with other agents including calcium channel blockers and hydrochlorothiazide. At present aliskiren is available as a fixed combination with DPC-423 hydrochlorothiazide in several dose strengths ie 150 mg 150 mg 300 mg and 300/25 mg and is approved as second-line treatment in patients whose blood pressure is not adequately DPC-423 controlled by the individual drugs alone. This review focuses on the efficacy of the combination of aliskiren with hydrochlorothiazide as a potential first-line treatment of hypertension. Renin-angiotensin-aldosterone inhibitors The RAAS is a system of active peptides and enzymes mainly DPC-423 responsible for fluid and electrolyte homeostasis and vascular tone (see Figure 1). Furthermore RAAS plays an important role in inflammation cellular and organ hypertrophy and fibrosis and activation of this system is therefore important in the pathophysiology of cardiovascular diseases including hypertension myocardial infarction heart and kidney failure.