Aliskiren stellt als Renin-Inhibitor die erste Substanz einer neuen Wirkstoffklasse zur pharmakologischen Intervention des Renin-Angiotensin-Systems dar. Aliskiren wurde von der amerikanischen Food and Drug Administration (FDA) im März 2007 bzw. in Europa im August 2007 zur Therapie der arteriellen Hypertonie zugelassen. Es wird unter den Handelsnamen Tekturna® bzw. Rasilez® vertrieben. Zahlreiche klinische Untersuchungen konnten eine effektive Blutdrucksenkung durch Aliskiren nachweisen. Ob Aliskiren über die Blutdrucksenkung hinausgehende Morbiditäts- und Mortalitätsvorteile für Patienten erbringt, wird allerdings erst nach Durchführung von vergleichenden Langzeitstudien genauer beurteilt werden können. Zudem bleibt abzuwarten, ob es zu einer Indikationserweiterung für den Einsatz von Aliskiren kommt, wie es für andere Inhibitoren des Renin-Angiotensin-Systems der Fall war. Aktuelle Studien zum Einsatz bei der chronischen Herzinsuffizienz und der diabetischen Nephropathie zeigen in der Tat erste günstige Effekte von Aliskiren bei diesen Erkrankungen (Reduktion des Urin-Albumin/Kreatinin-Quotienten bzw. von NTproBNP).
Summary
Aliskiren, a renin inhibitor, is the first in a new class of drugs interfering with the renin angiotensin system. Aliskiren was approved by the US Food and Drug Administration (FDA) in March 2007, and in Europe in August 2007 for the treatment of hypertension (marketed as Tekturna® and Rasilez®, respectively). Several clinical trials demonstrated effective blood pressure reduction due to aliskiren treatment. Whether aliskiren exhibits morbidity and mortality benefits for patients beyond its blood pressure reduction capability, can only be judged after realization of comparative long-term clinical trials. Furthermore, it remains to be seen, whether the use of aliskiren will be indicated for treatment of additional diseases, as it was the case for other inhibitors of the renin angiotensin system. In fact, recent and ongoing clinical trials regarding heart failure and diabetic nephropathy demonstrated first beneficial effects of aliskiren in these conditions (reduction of urinary albumin/creatinine-ratio and NTproBNP, respectively).
1
Alderman M H, Madhavan S, Ooi W L. et al .
Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension.
The New England journal of medicine.
1991;
324
1098-1104
2
Andersen K, Weinberger M H, Egan B. et al .
Comparative efficacy and safety of aliskiren, an oral direct renin inhibitor, and ramipril in hypertension: a 6-month, randomized, double-blind trial.
Journal of hypertension.
2008;
26
589-599
4
Feldt S, Batenburg W W, Mazak I. et al .
Prorenin and renin-induced extracellular signal-regulated kinase 1/2 activation in monocytes is not blocked by aliskiren or the handle-region peptide.
Hypertension.
2008;
51
682-688
5
Gradman A H, Schmieder R E, Lins R L. et al .
Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients.
Circulation.
2005;
111
1012-1018
7
Menard J, Azizi M.
The difficult conception, birth and delivery of a renin inhibitor: controversies around aliskiren.
Journal of hypertension.
2007;
25
1775-1782
8
Nguyen G, Delarue F, Burckle C. et al .
Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin.
J Clin Invest.
2002;
109
1417-1427
9
Nussberger J, Wuerzner G, Jensen C, Brunner H R.
Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril.
Hypertension.
2002;
39
E1-8
10
Oh B H, Mitchell J, Herron J R. et al .
Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension.
Journal of the American College of Cardiology.
2007;
49
1157-1163
11
Oparil S, Yarows S A, 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
221-229
12 Parving H H, Lewis J B, Lewis E J, Hollenberg N K. AVOID Aliskiren in the Evaluation of Proteinuria in Diabetes. American Society of Nephrology Renal Week Congress in San Francisco, Poster SA-P01051 California, USA 2007
13
Pilz B, Shagdarsuren E, Wellner M. et al .
Aliskiren, a human renin inhibitor, ameliorates cardiac and renal damage in double-transgenic rats.
Hypertension.
2005;
46
569-576
14
Recio-Mayoral A, Kaski J C, McMurray J J. et al .
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.
Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy.
2007;
21
459-465
15
Schefe J H, Menk M, Reinemund J. et al .
A novel signal transduction cascade involving direct physical interaction of the renin/prorenin receptor with the transcription factor promyelocytic zinc finger protein.
Circ Res.
2006;
99
1355-1366
16
Sealey J E, Laragh J H.
Aliskiren, the first renin inhibitor for treating hypertension: reactive renin secretion may limit its effectiveness.
Am J Hypertens.
2007;
20
587-597
18
Uresin Y, Taylor A A, 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
190-198
19
Villamil A, Chrysant S G, Calhoun D. et al .
Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide.
Journal of hypertension.
2007;
25
217-226
20
Weir M R, Bush C, Anderson D R. et al .
Antihypertensive efficacy, safety and tolerability of the oral renin inhibitor aliskiren in patients with hypertension: a pooled analysis.
J Am Soc Hypertension.
2007;
1
264-277
21
Wood J M, Maibaum J, Rahuel J. et al .
Structure-based design of aliskiren, a novel orally effective renin inhibitor.
Biochemical and biophysical research communications.
2003;
308
698-705
