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

Abstract

Patients with severe hypertension (4180/110 mm Hg) require large blood pressure (BP) reductions to reach recommended treatment goals (o140/90 mm Hg) and usually require combination therapy to do so. This 8-week, multicenter, randomized, double-blind, parallelgroup 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)X105 mm Hg and o120 mm Hg). In all, 183 patients were randomized (2:1) to aliskiren 150 mg (n ¼ 125) or lisinopril 20 mg (n ¼ 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 lisinoprilbased 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 À18.5 mm Hg vs LIS À20.1 mm Hg; mean treatment difference 1.7 mm Hg (95% confidence interval (CI) À1.0, 4.4)) and mean sitting systolic blood pressure (ALI À20.0 mm Hg vs LIS À22.3 mm Hg; mean treatment difference 2.8 mm Hg (95% CI À1.7, 7.4)). Responder rates (msDBPo90 mm Hg and/or reduction from baselineX10 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.

Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

“…Oncedaily treatment with aliskiren for 4 or 8 weeks has been shown to effectively decrease BP in patients with hypertension [178][179][180][181][182]. Additionally, dose-dependent decreases in BP were demonstrated during an 8-week treatment period of aliskiren monotherapy at 150, 300, and 600 mg, compared with placebo, in patients with mild to moderate hypertension [179].…”

The 2007 revised ESC/ESH Guidelines in the management of hypertension: clarifying individual patient care

“…Thus, regardless of the limited nature (or absence) of outcome studies they effectively lower blood pressure in combination and can be important in individual patients circumstances-as we recently highlighted for eplerenone. 4 Even oral renin inhibitors, a challenging concept under development for several decades, which has produced only one tenable agent (that is, aliskiren 5 ) for clinical use in man, can be accepted as valid in this setting.…”

Renin inhibition: the holy grail of renin–angiotensin system blockade?

“…The available evidence, such as that provided by Strasser et al, 1 suggests that aliskiren is a welltolerated and effective antihypertensive agent. However, is aliskiren better than the competition?…”

“…In this issue of the Journal of Human Hypertension, Strasser et al 1 present the results of a comparison of the direct renin inhibitor, aliskiren 150-300 mg daily and lisinopril 20-40 mg daily in severe hypertension. The treatments were similarly well tolerated (the primary end point) although the short duration of therapy meant that angiotensin-converting enzyme (ACE) inhibitor-induced cough was probably underestimated.…”