Efficacy and safety of aliskiren, a direct renin inhibitor, compared with ramipril in Asian patients with mild to moderate hypertension

Abstract

on behalf of the trial investigators 9This 8-week, randomized, double-blind, parallel-group study compared the efficacy and safety of aliskiren with ramipril in Asian patients with mild to moderate hypertension. Following a 2-to 3-week placebo run-in period, patients with mean sitting diastolic blood pressure (msDBP) X95 and o110 mm Hg were randomized to receive once daily dose of either aliskiren 75, 150, 300 mg or ramipril 5 mg for 8 weeks. Efficacy variables were the changes in msDBP and mean sitting systolic BP (msSBP) and BP control rates (o140/90 mm Hg). Safety was assessed by recording adverse events (AEs) and serious AEs (SAEs). Of 1316 randomized patients, 1160 (88.1%) completed the study. At the study endpoint, patients on aliskiren had greater mean BP reductions (14.39/11.63 mm Hg for 300 mg; 12.16/10.04 mm Hg for 150 mg; 12.24/10.66 mm Hg for 75 mg) than those on 5 mg ramipril (11.46/9.19 mm Hg). All aliskiren doses were statistically non-inferior (Po0.0001) to ramipril in reducing msDBP. The reduction in BP for aliskiren 300 mg was statistically superior vs. ramipril (Po0.002). Blood pressure control rates were higher for aliskiren (300 mg, 52.29%; 150 mg, 48.11%; 75 mg, 45.68%) than for ramipril (5 mg, 43.7%); the difference for aliskiren 300 mg vs. ramipril 5 mg was statistically significant (Po0.05). Aliskiren was well tolerated with a fourfold lower incidence of cough (0.6-1.2%) compared with ramipril (5.2%). SAEs were rare in this study (0.5%). Aliskiren produced greater BP reductions with a lower incidence of cough than ramipril in Asian patients with mild to moderate hypertension. Hypertension Research (2012) 35, 28-33; doi:10.1038/hr.2011.150; published online 8 September 2011Keywords: aliskiren; Asian; cough; ramipril INTRODUCTION Despite advances in the diagnosis and treatment of hypertension, only about 5-33% of patients achieve blood pressure (BP) control (o140/ 90 mm Hg) globally. Blood pressure control rates for the Asian population range from 9.5 to 36.6%, and in China, the rates have been estimated to be as low as 9.5%. This is of particular concern because of the increasing prevalence of hypertension (15-35%) in the Asian populations. [1][2][3][4][5][6][7] Of the many available antihypertensive drugs, angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers that act on the renin angiotensin-aldosterone system form the mainstay of therapy today. 2,8 However, incomplete blockade of renin angiotensin-aldosterone system by these agents results in an increase in plasma renin activity and potentially limits the therapeutic benefits of these drugs. 9 Moreover, ACE inhibition also results in suppression of kininase II, which may be followed by accumulation of the protussive mediators bradykinin and substance P in the upper respiratory tract or lungs. This results in undesirable adverse effects,

Finding a place for aliskiren in the wide spectrum of blood pressure lowering agents

“…Overall, systolic BP was lower with aliskiren than with ramipril (weighted mean difference between the treatments 1.84 mm Hg (Po0.0001) and 1.87 mm Hg (P¼0.0055) for fixed and random effect models, respectively); the standardized mean difference between the treatments was 2.58 (fixed effect model; Po0.0001) and 2.92 (random effect model; P¼0.0017) in favour of aliskiren. 9 In this context, the randomized, doubleblind, parallel-group study of Zhu et al 10 in the current issue of the Journal provides some additional data on the comparison of aliskiren with ramipril. Eligible patients enrolled across multiple centers in China, Thailand and India were randomly allocated to a oncedaily treatment with one of the following regimens: aliskiren 300 mg, 150 mg, 75 mg or ramipril 5 mg.…”

“…In addition, the proportion of patients who reached the BP target (o140/90 mm Hg) was higher in all three aliskiren dose groups (300 mg: 52.29%; 150 mg: 48.11%; 75 mg: 45.68%) compared with ramipril 5 mg (43.65%) with the difference between aliskiren 300 mg and ramipril 5 mg being statistically significant (P¼0.0177). 10 Although the number of randomized patients (n¼1160) was superior to previous studies that compared aliskiren with ramipril and the efficacy variables (changes in systolic and diastolic BP, pulse pressure and mean arterial pressure) were appropriately analyzed, some aspects of this study deserve specific comment.…”

Safety and Efficacy of Aliskiren in the Treatment of Hypertension and Associated Clinical Conditions

“…The efficacy of aliskiren on BP reduction in hypertensive patients has been evaluated in several clinical trials [14,. In placebo-controlled studies, aliskiren showed a doserelated systolic/diastolic BP lowering effect at doses between 75 and 300 mg/day [49].…”

“…Although the efficacy of Aliskiren on blood pressure (BP) reduction was confirmed in several trials [12][13][14], the early termination of the Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (ALTITUDE) [15,16] opened a debate on the real benefits from Aliskiren therapy in patients with diabetes and renal impairment.…”

Aliskiren and losartan trial in non-diabetic chronic kidney disease

“…7 The initial trials of aliskiren involved patients with hypertension, the drug being first developed as an antihypertensive agent. They were short trials in hypertensive patients, [8][9][10][11][12][13][14] many lasting only 8 weeks, and did not address the question of renoprotection. Later trials by Parving et al 5,8 and Tang et al 9 were conducted in patients with kidney disease, diabetes and IgA nephropathy, and these trials lasted longer -6 months and 12 months -and both showed a reduction of proteinuria, an indicator of renoprotection.…”