Aliskiren: An Overview of the First Direct Renin Inhibitor
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Optimal blockade of the renin-angiotensin-aldosterone system (RAAS) is a key goal of pharmacotherapy in cardiovascular (CV) and renal disease. Aliskiren, the first commercially available direct renin inhibitor, constitutes a new target in RAAS blockade. Since renin-catalyzed conversion of angiotensinogen into angiotensin I is the rate-limiting step in the synthesis of angiotensin II (AII), it has been suggested that renin inhibition may have comparable or superior clinical efficacy to angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB).
Aliskiren, which was approved by the FDA in 2007 for the treatment of hypertension, has a high specificity for renin and blocks the binding of angiotensinogen. It has a bioavailability of 2.6%, a serum peak at 2–4 h, and a half-life of 24–36 h. An analysis of seven randomized multicenter studies showed that overall incidence of adverse events with aliskiren monotherapy was similar to placebo, and an increased risk of d ...
- Weir MR, Bush C, Anderson DR, et al. Antihypertensive efficacy, safety, and tolerability of the oral direct renin inhibitor aliskiren in patients with hypertension: a pooled analysis. J Am Soc Hypertens 2007;1:264–77. CrossRef
- Oh BH, Mitchell J, Herron JR, et al. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol 2007;49:1157–63. CrossRef
- Kushiro T, Itakura H, Abo Y, et al. Aliskiren, a Novel Oral Renin Inhibitor, Provides Dose-Dependent Efficacy and Placebo-Like Tolerability in Japanese Patients with Hypertension. Hypertens Res 2006;29:997–1005. CrossRef
- Dahlöf B, Anderson DR, Arora V, et al. Aliskiren, a direct renin inhibitor, provides antihypertensive efficacy and excellent tolerability independent of age or gender in patients with hypertension. J Clin Hypertens 2007;9(Suppl A):A157.
- Stanton A, Jensen C, Nussberger J, et al. Blood pressure lowering in essential hypertension with an oral renin inhibitor, aliskiren. Hypertension 2003;42:1137–43. CrossRef
- Gradman AH, Schmieder RE, Lins RL, et al. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation 2005;8:1012–8. CrossRef
- Villamil A, Chrysant SG, Calhoun D, et al. Renin inhibiton with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens 2007;25:217–26. CrossRef
- Jordan J, Engeli S, Boye SW, et al. Direct renin inhibition with aliskiren in obese patients with arterial hypertension. Hypertension 2007;49:1047–55. CrossRef
- Uresin Y, Taylor AA, Kilo C, et al. Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension. J Renin Angiotensin Aldosterone Syst 2007;8:190–8. CrossRef
- Oparil S, Yarows SA, Patel S, et al. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet 2007;370:221–9. CrossRef
- Pool JL, Schmieder RE, Azizi M, et al. Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan. Am J Hypertens 2007;20:11–20. CrossRef
- Drummond W, Munger MA, Essop MR, et al. Anithypertensive efficacy of the oral direct renin inhibitor aliskiren as add-on therapy in patients not responding to amlodipine monotherapy. J Clin Hypertens 2007;9:742–50. CrossRef
- Dietz R, Dechend R, Yu C-M, et al. Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension. J Renin Angiotensin Aldosterone Syst 2008;9:163–75. CrossRef
- Musini VM, Fortin PM, Bassett K, et al. Blood pressure lowering efficacy of renin inhibitors for primary hypertension. Cochrane Database Syst Rev. 2008;Oct 8(4):CD007066.
- Seed A, Gardner R, McMurray J, et al. Neurohumoral effects of the new orally active renin inhibitor, aliskiren, in chronic heart failure. Eur J Heart Fail 2007;9:1120–27. CrossRef
- Recio-Mayoral A, Kaski JC, McMurray JJ. Clinical trials update from the European Society of Cardiology Congress in Vienna, 2007: PROSPECT, EVEREST, ARISE, ALOFT, FINESSE, Prague-8, CARESS in MI and ACUITY. Cardiovasc Drugs Ther 2007;21:459–65. CrossRef
- http://clinicaltrials.gov/ct/show/NCT00549757 NLM identifier: NCT00549757.
- http://clinicaltrials.gov/ct/show/NCT00414609 NLM identifier: NCT00414609.
- Data on file. Novartis Pharmaceuticals Corporation. East Hanover, NJ 07936.
- Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting–enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456–62. CrossRef
- Ruggenenti P, Fassi A, Ilieva AP, et al. Preventing Microalbuminuria in Type 2 Diabetes. N Engl J Med 2004;351:1941–51. CrossRef
- Parving HH, Lehnert H, Bröchner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870–8. CrossRef
- Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851–60. CrossRef
- Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861–9. CrossRef
- Rossing K, Schjoedt KJ, Jensen BR, et al. Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria. Kidney Int 2005;68:1190–8. CrossRef
- Mogensen CE, Neldam S, Tikkanen I, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 2000;321:1440–4. CrossRef
- Rossing K, Pietraszek L, Jacobsen P, Parving HH. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial. Diabetes Care 2003;26:2268–74. CrossRef
- Kunz R, Friedrich C, Wolbers M, et al. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin–angiotensin system on proteinuria in renal disease. Ann Intern Med 2008;148:30–48.
- Rossing K, Schjoedt KJ, Smidt UM, et al. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study. Diabetes Care 2005;28:2106–12. CrossRef
- Schjoedt KJ, Rossing K, Juhl TR, et al. Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy. Kidney Int 2006;70:536–42.
- Epstein M. Aldosterone receptor blockade and the role of eplerenone: evolving perspectives. Nephrol Dial Transplant 2003;18:1984–92. CrossRef
- Parving HH, Persson F, Lewis JB, et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008;358:2433–46. CrossRef
- Panesar M, Damodar A, Lindner T, et al. Correspondence. N Engl J Med 2008;359:1068–70. CrossRef
- Bakris G, Burgess E, Weir M, et al. Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy. Kidney Int 2008;74:364–9. CrossRef
- Nishimura T, Hashimoto J, Ohkubo T, et al. Efficacy and duration of action of the four selective angiotensin II subtype 1 receptor blockers, losartan, candesartan, valsartan and telmisartan, in patients with essential hypertension determined by home blood pressure measurements. Clin Exp Hypertens 2005;6:477–89. CrossRef
- Aliskiren: An Overview of the First Direct Renin Inhibitor
Volume 18, Issue 3 , pp 117-120
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links