Aliskiren

Brown, Morris J.

doi:10.1161/circulationaha.108.787630

Cited by 119 publications

(107 citation statements)

References 59 publications

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“…[13][14][15] Aliskiren, an oral direct renin inhibitor, has been shown to be effective in lowering arterial BP as monotherapy or in combination with other anti-hypertensive drugs. [16][17][18] To date, aliskiren has not been prospec-tively evaluated in a controlled study in elderly patients with systolic hypertension. The purpose of this study (Aliskiren for GEriatric LowEring of SyStolic Hypertension: The AGELESS trial) was to compare the efficacy and safety of the direct renin inhibitor aliskiren compared with the ACE inhibitor ramipril for the treatment of essential systolic hypertension in elderly patients.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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“…Aliskiren is the first in a new class of orally effective direct renin inhibitors, and blocks the RAS in different pharmacological mechanisms from those of conventional RAS blockers [10,11]. Aliskiren not only lowers BP in hypertensive animals and patients [12,13] but also has been recently reported to attenuate cardiovascular and renal injuries in various animal disease models [14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Aliskiren prevents cardiovascular complications and pancreatic injury in a mouse model of obesity and type 2 diabetes

et al. 2009

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Aims/hypothesis The effect of renin inhibition on type 2 diabetes is still unclear. The present study was undertaken to examine the efficacy of aliskiren, a direct renin inhibitor, on cardiovascular injuries, glucose intolerance and pancreatic injury in a mouse model of type 2 diabetes. Methods Groups of db/db mice, with obesity and type 2 diabetes, were treated with aliskiren (3, 6, 12 and 25 mg kg −1 day −1 ) or hydralazine (80 mg kg −1 day −1 ) for 6 weeks, and the protective effects were extensively compared among groups.Results All sub-pressor and hypotensive doses of aliskiren significantly attenuated cardiac fibrosis, macrophage infiltration and coronary remodelling, and improved vascular endothelial function in db/db mice. These protective effects of aliskiren were attributed to the attenuation of cardiac p22 phox -related NADPH oxidase-induced superoxide and the restoration of vascular endothelial nitric oxide synthase (eNOS) production. Aliskiren at the highest dose (25 mg kg), but not at lower doses, partially reduced glucose intolerance in db/db mice. Furthermore, the highest dose of aliskiren significantly attenuated the decreases in pancreatic islet insulin content and beta cell mass, and prevented pancreatic islet fibrosis in db/db mice, being associated with the reduction of 8-hydroxy-2′-deoxyguanosine-positive cells and Nox2 (also known as Cybb) expression in pancreatic islets by aliskiren. Conclusions/interpretation Our work provides the first evidence that direct renin inhibition with aliskiren protects against cardiovascular complications and pancreatic injury, through the attenuation of oxidative stress. Thus, we propose that aliskiren may be a promising therapeutic agent for type 2 diabetes.

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“…In these patients, aliskiren was extremely well tolerated and effective in lowering blood pressure and improving intermediate measures of outcome such as proteinuria, left ventricular hypertrophy and biochemical markers of heart failure. 6,15 Notably, the efficacy of aliskiren in the above clinical conditions was evident on top of standard therapy, thus remarking the concept that a complete blockade of the renin-angiotensin-system at its first rate-limiting step may be beneficial in specific categories of patients. The long duration of action, which makes this drug suitable for once-daily administration, and the hepatic site of metabolism, which makes the drug indicated also in patients with renal failure, are further good news from this promising drug.…”

Section: Discussionmentioning

confidence: 99%

Good News from Aliskiren?

Verdecchia

Angeli

Reboldi

2009

Clinical Medicine. Therapeutics

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Abstract:The renin-angiotensin system can be inhibited through inhibition of angiotensin I generation from angiotensinogen by direct renin inhibitors, inhibition of angiotensin II generation from angiotensin I by angiotensin-converting enzyme inhibitors and by direct inhibition of the action of angiotensin II receptor level. Aliskiren, the first direct renin inhibitor to reach the market, is a low molecular weight, orally active, hydrophilic nonpeptide. It blocks angiotensin I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by angiotensin II on renin synthesis. Aliskiren is suitable for once-daily administration because of its long pharmacological half-life. Because of its mechanism of action, aliskiren may provide the additional opportunity to inhibit progression of atherosclerosis at tissue level. Hypertension is an approved indication for aliskiren, which is also promising for the treatment of heart failure and diabetic nephropathy. The efficacy of this drug on major clinical events is being tested in large ongoing clinical trials.

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Aliskiren

Cited by 119 publications

References 59 publications

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

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

Aliskiren prevents cardiovascular complications and pancreatic injury in a mouse model of obesity and type 2 diabetes

Good News from Aliskiren?

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