A comparison of the tolerability of the direct renin inhibitor aliskiren and lisinopril in patients with severe hypertension.

Patients with severe hypertension (>180/110 mm Hg) require large blood pressure (BP) reductions to reach recommended treatment goals (<140/90 mm Hg) and usually require combination therapy to do so. This 8-week, multicenter, randomized, double-blind, parallel-group study compared the tolerability and antihypertensive efficacy of the novel direct renin inhibitor aliskiren with the angiotensin converting enzyme inhibitor lisinopril in patients with severe hypertension (mean sitting diastolic blood pressure (msDBP)>or=105 mm Hg and <120 mm Hg). In all, 183 patients were randomized (2:1) to aliskiren 150 mg (n=125) or lisinopril 20 mg (n=58) with dose titration (to aliskiren 300 mg or lisinopril 40 mg) and subsequent addition of hydrochlorothiazide (HCTZ) if additional BP control was required. Aliskiren-based treatment (ALI) was similar to lisinopril-based treatment (LIS) with respect to the proportion of patients reporting an adverse event (AE; ALI 32.8%; LIS 29.3%) or discontinuing treatment due to AEs (ALI 3.2%; LIS 3.4%). The most frequently reported AEs in both groups were headache, nasopharyngitis and dizziness. At end point, ALI showed similar mean reductions from baseline to LIS in msDBP (ALI -18.5 mm Hg vs LIS -20.1 mm Hg; mean treatment difference 1.7 mm Hg (95% confidence interval (CI) -1.0, 4.4)) and mean sitting systolic blood pressure (ALI -20.0 mm Hg vs LIS -22.3 mm Hg; mean treatment difference 2.8 mm Hg (95% CI -1.7, 7.4)). Responder rates (msDBP<90 mm Hg and/or reduction from baseline>or=10 mm Hg) were 81.5% with ALI and 87.9% with LIS. Approximately half of patients required the addition of HCTZ to achieve BP control (ALI 53.6%; LIS 44.8%). In conclusion, ALI alone, or in combination with HCTZ, exhibits similar tolerability and antihypertensive efficacy to LIS alone, or in combination with HCTZ, in patients with severe hypertension.