Aliskiren for Geriatric Lowering of Systolic Hypertension: a randomized controlled trial

Abstract

Efficacy and safety of the direct renin inhibitor aliskiren was compared with ramipril for treatment of essential systolic hypertension in elderly patients. A 36-week, randomized, double-blind, parallel-group, active-controlled, optional-titration study was performed in 901 patients (aliskiren, n ¼ 457; ramipril, n ¼ 444) X65 years of age with systolic blood pressure (SBP) X140 mm Hg. Aliskiren 150-300 mg per day or ramipril 5-10 mg per day for was administered for 12 weeks with optional add-on therapy of hydrochlorothiazide (12.5-25 mg per day) at week 12 and amlodipine (5-10 mg per day) at week 22. The primary end point was non-inferiority of aliskiren vs ramipril monotherapy for change from baseline in mean sitting SBP (msSBP) at week 12. Decreases from baseline msSBP and mean sitting diastolic BP with aliskiren monotherapy (À14.0 and À5.1 mm Hg, respectively) were non-inferior (Po0.001 for both values) and superior to ramipril monotherapy (À11.6, À3.6 mm Hg; P ¼ 0.02, Po0.01, respectively). More patients achieved BP control with aliskiren (42%) than ramipril (33%; Po0.01). At week 36, fewer patients receiving aliskiren-based therapy required add-on treatment with hydrochlorothiazide or amlodipine (P ¼ 0.01 and 0.048, respectively). Tolerability was similar, but more patients receiving ramipril reported cough (Po0.001). In elderly patients with systolic hypertension, aliskiren proved to be more effective and better overall anti-hypertensive therapy compared to ramipril.

Direct renin inhibition: extricating facts from façades

“…For example, in the AGELESS study, aliskiren therapy was associated with a lesser incidence of adverse effects compared with ramipril (70% less undesired effects with aliskiren, compared with ramipril) [Duprez et al 2010] In summary, in light of new knowledge on RAS components, the approach to high blood pressure treatment continues developing encouragingly. Among all available agents, those inhibiting the RAS show clear pathogenic and pharmacokinetic advantages, as well as an excellent tolerability profile.…”

“…For instance, the AGELESS Trial (Aliskiren for Geriatric Lowering of Systolic Hypertension) showed that aliskiren (either as monotherapy or combined with hydrochloro-thiazide) is more effective than ramipril at reducing systolic and diastolic blood pressure in patients older than 65 years with systolic hypertension [Duprez et al 2010].…”

Updated Report on Comparative Effectiveness of ACE inhibitors, ARBs, and Direct Renin Inhibitors for Patients with Essential Hypertension: Much More Data, Little New Information

“…Two good-quality RCTs compared the DRI aliskiren at a maximum dose of 300 mg to the ACE inhibitor ramipril at a maximum dose of 10 mg. [11][12][13] In both studies, aliskiren produced a greater reduction in blood pressure at 12 weeks, with between-group blood pressure (SBP/ DBP) differences of −2.7/-1.6…”

“…Thirty studies (11 new, including two evaluating a DRI) presented original results on either serum creatinine/ GFR, 13,19,22,28,33,43,59,72,82,87,91,92 proteinuria, 11,29,58,60,80,103 or both. 23,30,46,49,56,62,65,73,81,97,99,102 The ten new studies that described changes in creatinine or glomerular filtration rate did not consistently demonstrate differential effects with use of ACE inhibitors versus ARBs, nor did the two studies comparing a DRI with the ACE inhibitor ramipril; 11,13 these findings were similar to those from the 2007 report.…”

“…[11][12][13][14]17,27,31,34,40,42,[44][45][46][47]49,[51][52][53]58,60,63,71,[73][74][75][76][89][90][91][92]98 Sample sizes ranged from 30 to 13,303 patients. The rates of successful blood pressure control with a single agent ranged from 6% to 93.3% (median 55%).…”