First-line treatment of hypertension: critical appraisal of potential role of aliskiren and hydrochlorothiazide in a fixed combination Konstantinos Savvatis1, Dirk Westermann1, Heinz-Peter Schultheiss1, Carsten Tschöpe1,21Charité Universitätsmedizin Berlin, Department of Cardiology and Pneumonology, Campus Benjamin Franklin, Berlin; 2Charité Universitätsmedizin Berlin, Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow-Klinikum, Berlin, GermanyAbstract: Arterial hypertension is one of the major diseases in the Western world. It is an independent cardiovascular risk factor and is associated with increased morbidity and mortality. Several drug classes have been shown to be effective in the treatment of hypertension. Aliskiren is a direct renin inhibitor and belongs to the class of renin-angiotensin-aldosterone system inhibitors. Several large studies have shown that aliskiren is effective in lowering blood pressure, and equivalent in this respect to the angiotensin-converting enzyme (ACE) inhibitors and the angiotensin receptor-1 blockers (ARBs). Furthermore, aliskiren has a safety and tolerability profile comparable with that of the ARBs and slightly better than that of the ACE inhibitors. From a pathophysiologic perspective, it can be combined with hydrochlorothiazide 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