Resumen
El bloqueo a distintos niveles del sistema renina-angiotensina ha demostrado importantes beneficios en la reducción de la morbimortalidad cardiovascular. La introducción en el arsenal terapéutico del aliskiren, un inhibidor directo de la renina, ha abierto una nueva vía para el tratamiento de la hipertensión y la protección de los órganos diana. El aliskiren tiene una eficacia antihipertensiva similar a la de otros fármacos antihipertensivos, con un perfil de seguridad y tolerabilidad comparable al del placebo, incluido el tratamiento de hipertensos diabéticos obesos y pacientes de edad avanzada, con reducción persistente de la presión arterial y una supresión prolongada de la activación de renina plasmática, incluso tras la retirada del fármaco. Los datos disponibles de diferentes estudios clínicos y experimentales indican que el aliskiren es capaz de proteger contra el daño de los órganos diana, especialmente en pacientes diabéticos. Los prometedores resultados de los ensayos clínicos realizados con aliskiren en pacientes hipertensos, que evalúan marcadores de daño orgánico renal y cardiaco, refrendan la importancia de inhibir el sistema renina-angiotensina-aldosterona cuando se busca reducir la morbimortalidad cardiovascular y renal. El actual programa de ensayos clínicos ASPIRE HIGHER está diseñado para evaluar indirecta (acciones sobre diferentes marcadores) y directamente (efectos en diferentes órganos diana) la capacidad organoprotectora del aliskiren; los resultados que se obtengan definirán el papel de la inhibición directa de la renina en el tratamiento de la hipertensión arterial y, sobre todo, en la reducción de la morbimortalidad cardiovascular.
Palabras clave
Aliskiren
Hipertrofia ventricular izquierda
Nefropatía diabética
Hipertensión arterial
Este artículo solo puede leerse en
pdf
Bibliografía
[1.]
M.A. Weber, T.D. Giles.
Inhibiting the renin-angiotensin system to prevent cardiovascular disorders: Do we need a more comprehensive strategy.
Rev Cardiovasc Med, (2006), 7 pp. 45-54
[2.]
B.H. Oh, J. Mitchell, J.R. Herron, J. Chung, M. Khan, D.L. Keefe.
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 pp. 1157-1163
[3.]
H. Rashid.
Direct renin inhibition: an evaluation of the safety and tolerability of Aliskiren.
Curr Med Res Opin, (2008), 24 pp. 2627-2637
[4.]
A.H. Gradman, R. Pinto, R. Kad.
Current concepts: Renin inhibition in the treatment of hypertension.
Curr Opin Pharmacol, (2008), 8 pp. 120-126
[5.]
Y. Uresin, A.A. Taylor, C. Kilo, D. Tschöpe, M. Santonastaso, G. Ibram, 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 pp. 190-198
[6.]
J. Jordan, S. Engeli, S.W. Boye, S. Le Breton, D.L. Keefe.
Direct renin inhibition with Aliskiren in obese patients with arterial hypertension.
Hypertension, (2007), 49 pp. 1047-1055
[7.]
P. Verdecchia, C. Calvo, V. Mockel, L. Keeling, A. Satlin.
Safety and efficacy of the oral direct renin inhibitor Aliskiren in elderly patients with hypertension.
Blood Press, (2007), 16 pp. 381-391
[8.]
ASPIRE HIGHER clinical program expands to 35,000 patients in 14 trials, the largest cardio-renal outcomes program ever [citado 25 Jun 2010]. Disponible en: http://www.novartis.be/downloads/nl/pers-media/berichten/reports/2008-07-17_financialreport_s1-2008_en.pdf
[9.]
G.B. Mancini, B. Dahlof, J. Diez.
Surrogate markers for cardiovascular disease: Structural markers.
Circulation, (2004), 109 pp. IV22-IV30
[10.]
S.D. Solomon, E. Appelbaum, W.J. Manning, A. Verma, T. Berglund, V. Lukashevich, Aliskiren in Left Ventricular Hypertrophy (ALLAY) Trial Investigators, et al.
Effect of the direct renin inhibitor Aliskiren, the angiotensin receptor blocker losartan, or both on left ventricular mass in patients with hypertension and left ventricular hypertrophy.
Circulation, (2009), 119 pp. 530-537
[11.]
D. Westermann, A. Riad, O. Lettau, A. Roks, K. Savvatis, P.M. Becher, et al.
Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure.
Hypertension, (2008), 52 pp. 1068-1075
[12.]
Solomon SD. Effect of the direct renin inhibitor Aliskiren on left ventricular remodelling following myocardial infarction with left ventricular dysfunction: ASPIRE. Presented at: American College of Cardiology 59th Annual Scientific Sessions; Atlanta, GA. Mar 13–16, 2010.
[13.]
ONTARGET. Investigators, S. Yusuf, K.K. Teo, J. Pogue, L. Dyal, I. Copland, H. Schumacher, et al.
Telmisartan, ramipril or both in patients at high risk for vascular events.
N Engl J Med, (2008), 358 pp. 1547-1559
[14.]
B.M. Scirica, D.A. Morrow, C. Bode, W. Ruzyllo, M. Ruda, A. Oude Ophuis, et al.
Patients with acute coronary syndromes and elevated levels of natriuretic peptides: the results of the AVANT GARDE-TIMI 43 Trial.
Eur Heart J, (2010), 31 pp. 1993-2005
[15.]
A. Seed, R. Gardner, J. McMurray, C. Hillier, D. Murdoch, R. MacFadyen, et al.
Neurohumoral effects of the new orally active renin inhibitor. Aliskiren, in chronic heart failure.
Eur J Heart Fail, (2007), 9 pp. 1120-1127
[16.]
J. McMurray, B. Pitt, R. Latini, Maggioni Ap, S.D. Solomon, D.L. Keefe, Aliskiren Observation of Heart Failure Treatment (ALOFT) Investigators, et al.
Effects of the oral direct renin inhibitor Aliskiren in patients with symptomatic heart failure.
Circ Heart Fail, (2008), 1 pp. 17-24
[17.]
McMurray JJV. Haemodynamic, neurohumoral, renal and ambulatory electrocardiographic effects of a new oral renin inhibitor in stable heart failure. Oral presentation at European Society of Cardiology Congress, Vienna, Austria. 1-5 September 2007.
[18.]
R. Latini, S. Masson, I. Anand, D. Judd, A.P. Maggioni, Y.T. Chiang, Valsartan Heart Failure Trial Investigators, et al.
Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure: The Valsartan Heart Failure Trial (Val-HeFT).
Circulation, (2002), 106 pp. 2454-2458
[19.]
T.H. Jafar, P.C. Stark, C.H. Schmid, M. Landa, G. Maschio, C. Marcantoni, AIPRD Study Group, et al.
Angiotensin-converting enzymne inhibition and progression of renal disease. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease.
Kidney Int, (2001), 60 pp. 1131-1140
[20.]
K. Klausen, K. Borch-Johnsen, B. Feldt-Rasmussen, G. Jensen, P. Clausen, H. Scharling, et al.
Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes.
Circulation, (2004), 110 pp. 32-35
[21.]
II Conferencia Internacional New Insights: progresión de la enfermedad renal crónica. Barcelona: Sociedad Española de Nefrología (SEN); 2005.
[22.]
H.H. Parving, H.A.E. Jensen, C.E. Mogensen, P.E. Evrin.
Increased urinary albumin excretion rate in benign essential hypertension.
Lancet, (1974), 1 pp. 1190-1192
[23.]
K. Watchell, H. Ibsen, M.H. Olsen, K. Borch-Johnsen, L.H. Lindholm, C.E. Mogensen, et al.
Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study.
Ann Intern Med, (2003), 139 pp. 901-906
[24.]
H.C. Gerstein, J.F.E. Mann, Q. Yi, B. Zinman, S.F. Dinneen, B. Hoogwerf, HOPE Study Investigators, et al.
Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.
JAMA, (2001), 286 pp. 421-426
[25.]
J.P. Casas, W. Chua, S. Loukogeorgakis, P. Vallance, L. Smeeth, A.D. Hingorani, et al.
Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis.
Lancet, (2005), 366 pp. 2026-2033
[26.]
H. Ibsen, M.H. Olsen, K. Wachtell, K. Borch-Johnsen, L.H. Lindholm, C.E. Mogensen, et al.
Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: Losartan Intervention For Endpoint reduction in hypertension study.
Hypertension, (2005), 45 pp. 198-202
[27.]
G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, et al.
Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
J Hypertens, (2007), 25 pp. 1105-1187
[28.]
2010 Canadian Hypertension Education Program (CHEP). Disponible en: http://hypertension.ca/chep
[29.]
B.M. Brenner, M.E. Cooper, D. De Zeeuw, W.F. Keane, W.E. Mitch, H.H. Parving, RENAAL Study Investigators, et al.
Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.
N Engl J Med, (2001), 345 pp. 861-869
[30.]
E.J. Lewis, L.G. Hunsicker, W.R. Clarke, T. Berl, M.A. Pohl, J.B. Lewis, Collaborative Study Group, 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 pp. 851-860
[31.]
H.H. Parving, H. Lehnert, J. Brochner-Mortensen, R. Gomis, S. Andersen, P. Arner.
The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.
N Engl J Med, (2001), 345 pp. 870-878
[32.]
P. Jacobsen, S. Andersen, K. Rossing, B.R. Jensen, H.H. Parving.
Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy.
Kidney Int, (2003), 63 pp. 1874-1880
[33.]
N. Nakao, A. Yoshimura, H. Morita, M. Takada, T. Kayano, T. Ideura.
Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial.
Lancet, (2003), 361 pp. 117-124
[34.]
J.F. Mann, R.E. Schmieder, M. McQueen, L. Dyal, H. Schumacher, J. Pogue, ONTARGET investigaros, et al.
Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial.
Lancet, (2008), 372 pp. 547-553
[35.]
F. Persson, P. Rossing, H. Reinhard, T. Juhl, C.D. Stehouwer, C. Schalwijk, et al.
Renal effects of Aliskiren compared with and in combination with irbesartan in patients with Type 2 diabetes, hypertension and albuminuria.
Diabetes Care, (2009), 32 pp. 1873-1879
[36.]
H.H. Parving, F. Persson, J.B. Lewis, E.J. Lewis, N.K. Hollenberg, for the AVOID Study Investigators.
Aliskiren combined with losartan in Type 2 Diabetes and Nephropathy.
N Engl J Med, (2008), 358 pp. 2433-2446
[37.]
M.J. Buxton, M.F. Drummond, B.A. Van Hout, R.L. Prince, T.A. Sheldon, T. Szucs, et al.
Modelling in economic evaluation: an unavoidable fact of life.
Health Econ, (1997), 6 pp. 217-227
[38.]
D.J. Cohen, M.R. Reynolds.
Interpreting the results of cost-effectiveness studies.
J Am Coll Cardiol, (2008), 52 pp. 2119-2126
[39.]
M. Brosa, M. De la Figuera, J. Franch, J. Segura, M. Riera, M. Figueras.
Análisis costeefectividad de aliskiren en pacientes hipertensos, con diabetes tipo 2 y nefropatía ya tratados de forma óptima con ARA-II y otros fármacos antihipertensivos.
PharmacoEconomics-Spanish Research Articles, (2009), 6 pp. 95-104
[40.]
J. López Bastida, J. Oliva, F. Antoñanzas.
Propuesta de guía para la evaluación económica aplicada a las tecnologías sanitarias. Madrid: Plan Nacional para el SNS del MSC. Servicio de Evaluación del Servicio Canario de la Salud; 2008. Informes de Evaluación de Tecnologías Sanitarias: SESCS N° 2006/22. 41. Sacristán JA, Oliva J, Del Llano J, Prieto L, Pinto JL. [What is an efficient health technology in Spain?].
Gac Sanit, (2002), 16 pp. 334-343
[42.]
T.E. Delea, O. Sofrygin, J.L. Palmer, H. Lau, V.C. Munk, J. Sung, et al.
Cost-effectiveness of aliskiren in type 2 diabetes, hypertension, and albuminuria.
J Am Soc Nephrol, (2009), 20 pp. 2205-2213
[43.]
D.Z. Cherney, V. Lai, J.W. Scholey, J.A. Miller, B. Zinman, H.N. Reich.
The effect of direct renin inhibition on renal haemodynamic function, arterial stiffness and endothelial function in humans with uncomplicated Type 1 diabetes mellitus: A pilot study.
Diabetes Care, (2010), 33 pp. 361-365
[44.]
J. Nussberger, J.F. Aubert, K. Bouzourene, M. Pellegrin, D. Hayoz, L. Mazzolai.
Renin inhibition by aliskiren prevents atherosclerosis progression: Comparison with irbesartan, atenolol, and amlodipine.
Hypertension, (2008), 51 pp. 1306-1311
[45.]
T. Imanishi, H. Tsujioka, H. Ikejima, A. Kuroi, S. Takarada, H. Kitabata, et al.
Renin inhibitor Aliskiren improves impaired nitric oxide bioavailability and protects against atherosclerotic changes.
Hypertension, (2008), 52 pp. 563-572
[46.]
Safety and Efficacy of Aliskiren on the Progression of Atherosclerosis in Coronary Artery Disease Patients (AQUARIUS). ClinicalTrials.gov Identifier: NCT00853827.
[47.]
H.H. Parving, B.M. Brenner, J.J. McMurray, D. De Zeeuw, S.M. Haffner, S.D. Solomon, et al.
Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): Rationale and study design.
Nephrol Dial Transplant, (2009), 24 pp. 1663-1671
[48.]
Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbimortality in Patients With Chronic Heart Failure (ATMOSPHERE). ClinicalTrials.gov Identifier: NCT00853658.
[49.]
Six Months Efficacy and Safety of Aliskiren Therapy on Top of Standard Therapy, on Morbidity and Mortality in Patients With Acute Decompensated Heart Failure (ASTRONAUT). ClinicalTrials.gov Identifier: NCT00894387.
Copyright ©
2011. Sociedad Española de Cardiología