Aliskiren: A new drug for an old problem

Cardiovascular and Hematological Agents in Medicinal Chemistry

Volumn 8, Issue 1, 2010, Pages 1-10

  Barrios, V ^a   Escobar, C ^b  

^a HOSPITAL RAMÓN Y CAJAL   (Spain)

^b HOSPITAL UNIVERSITARIO INFANTA SOFÍA   (Spain)

Author keywords

Aliskiren; Arterial hypertension; Cardiovascular; Heart failure; Microalbuminuria; Renin inhibition; Renin angiotensin aldosterone system

Indexed keywords

ALISKIREN; ALISKIREN PLUS HYDROCHLOROTHIAZIDE; AMLODIPINE; FUROSEMIDE; HYDROCHLOROTHIAZIDE; IRBESARTAN; KETOCONAZOLE; LOSARTAN; PLACEBO; RAMIPRIL; TELMISARTAN; VALSARTAN;

ADD ON THERAPY; ANGIONEUROTIC EDEMA; ATHEROSCLEROSIS; BACKACHE; CARDIOVASCULAR RISK; CLINICAL TRIAL; CREATININE BLOOD LEVEL; DIABETES MELLITUS; DIABETIC NEPHROPATHY; DIARRHEA; DIASTOLIC BLOOD PRESSURE; DIZZINESS; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE TITRATION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG STRUCTURE; DRUG TOLERABILITY; FATIGUE; GASTROINTESTINAL DISEASE; HEADACHE; HEART FAILURE; HEART INFARCTION; HEART LEFT VENTRICLE HYPERTROPHY; HUMAN; HYPERKALEMIA; HYPERTENSION; MORBIDITY; MORTALITY; NEPHROLITHIASIS; NON INSULIN DEPENDENT DIABETES MELLITUS; PLASMA RENIN ACTIVITY; POTASSIUM BLOOD LEVEL; QT PROLONGATION; RASH; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RHINOPHARYNGITIS; SIDE EFFECT; STROKE; SYSTOLIC BLOOD PRESSURE; UREA NITROGEN BLOOD LEVEL; VASCULAR DISEASE;

AMIDES; ANTIHYPERTENSIVE AGENTS; CARDIOVASCULAR SYSTEM; CLINICAL TRIALS AS TOPIC; DRUG THERAPY, COMBINATION; FUMARATES; HUMANS; HYPERTENSION; RENIN; RENIN-ANGIOTENSIN SYSTEM;

EID: 77950835357     PISSN: 18715257     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152510790796174     Document Type: Review

References (78)

1. Kannel, W.B. Blood pressure as a cardiovascular risk factor: prevention and treatment. JAMA, 1996, 275, 1571.
2. MacMahon, S.; Peto, R.; Cutlier, L.; Collins, R.; Sorlie, P.; Neaton, J.; Abbott, R.; Godwin, J.; Dyer, A.; Stamler, J. Blood pressure, stroke, and coronary heart disease: part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet, 1990, 335, 765.
3. Mancia, G.; De Backer, G.; Dominiczak, A.; Cifkova, R.; Fagard, R.; Germano, G.; Grassi, G.; Heagerty, A.M.; Kjeldsen, S.E.; Laurent, S.; Narkiewicz, K.; Ruilope, L.; Rynkiewicz, A.; Schmieder, R.E.; Boudier, H.A.; Zanchetti, A.; Vahanian, A.; Camm, J.; De Caterina, R.; Dean,V.; Dickstein, K.; Filippatos, G.; Funck-Brentano, C.; Hellemans, I.; Kristensen, S.D.; McGregor, K.;, Sechtem, U.; Silber, S.; Tendera, M.; Widimsky, P.; Zamorano, J.L.; Erdine, S.; Kiowski, W.; Agabiti-Rosei, E.; Ambrosioni, E.; Lindholm, L.H.; Viigimaa, M.; Adamopoulos, S.; Agabiti-Rosei, E.; Ambrosioni, E.; Bertomeu, V.; Clement, D.; Erdine, S.; Farsang, C.; Gaita, D.; Lip, G.; Mallion, J.M.; Manolis, A.J.; Nilsson, P.M.; O'Brien, E.; Ponikowski, P.; Redon, J.; Ruschitzka, F.; Tamargo, J.; van Zwieten, P.; Waeber, B.; Williams, B. 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, 1105.
4. Wang, Y.R.; Alexander, G.C.; Stafford, R.S. Outpatient hypertension treatment, treatment intensification, and control in Western Europe and the United States. Arch. Intern. Med. 2007, 767, 141.
5. Greathouse, M. Olmesartan medoxomil combined with hydrochlorothiazide for the treatment of hypertension. Vasc. Health. Risk. Manage., 2006, 2, 401.
6. Cheung, B.M.; Ong, K.L.; Man, Y.B.; Lam, K.S.; Lau, C.P. Prevalence, awareness, treatment, and control of hypertension: United States National Health and Nutrition Examination Survey 2001-2002. J. Clin. Hypertens. (Greenwich), 2006, 8, 93.
7. Barrios, V.; Banegas, J.R.; Ruilope, L.M.; Rodicio, J.L. Evolution of blood pressure control in Spain. J. Hypertens., 2007, 25, 1975.
8. European Society of Hypertension-European Society of Cardiology Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J. Hypertens., 2003, 27, 1011.
9. Chobanian, A.V.; Bakris, G.L.; Black, H.R.; Cushman, W.C.; Green, L.A.; Izzo, J.L., Jr.; Jones, D.W.; Materson, B.J.; Oparil, S.; Wright, J.T., Jr.; Roccella, E.J. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA, 2003, 289, 2560.
10. Barrios, V.; Escobar, C.; Calderón, A.; Echarri, R.; González-Pedel, V.; Ruilope, L.M.; CONTROLRISK Investigators. Cardiovascular risk profile and risk stratification of the hypertensive population attended by general practitioners and specialists in Spain. The CONTROLRISK study. J. Hum. Hypertens., 2007, 27, 479.
11. Motwani, J.G. Combining renin-angiotensin-aldosterone system blockade with diuretic therapy for treatment of hypertension. J. Renin. Angiotensin. Aldosterone. Syst., 2002, 3, 72.
12. Sica, D.A. Rationale for fixed-dose combinations in the treatment of hypertension: the cycle repeats. Drugs, 2002, 62, 44.
13. Escobar, C.; Echarri, R.; Barrios, V. Combined therapy in the treatment of hypertension: but which? J. Hypertens., 2009, 27, 1331.
14. Lazarus J.M.; Bourgoignie J.J.; Buckalew, V.M.; Greene, T.; Levey, A.S.; Milas, N.C.; Paranandi, L.; Peterson, J.C.; Porush, J.G.; Rauch, S.; Soucie, J.M.; Stollar, C. Achievement and safety of a low blood pressure goal in chronic renal disease. The Modification of Diet in Renal Disease Study Group. Hypertension, 1997, 29, 641.
15. Estacio, R.O.; Schrier, R.W. Antihypertensive therapy in type 2 diabetes: implications of the appropriate blood pressure control in diabetes (ABCD) trial. Am. J. Cardiol. 1998, 82, 9R-14R.
16. UKPDS 38. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ, 1998, 37 7, 703.
17. Hansson, L.; Zanchetti, A.; Carruthers, S.G.; Dahlöf, B.; Elmfeldt, D.; Julius, S.; Ménard, J.; Rahn, K.H.; Wedel, H.; Westerling, S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. Hot study group. Lancet, 1998, 357, 1755.
18. Bakris, G.L.; Williams, M.; Dworkin, L.; Elliott, W.J.; Epstein, M.; Toto, R.; Tuttle, K.; Douglas, J.; Hsueh, W.; Sowers, J. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National kidney foundation hypertension and diabetes executive committees working group. Am. J. Kidney. Dis., 2000, 36, 646.
19. Brenner, B.M.; Cooper, M.E.; de Zeeuw, D.; Keane, W.F.; Mitch, W.E.; Parving, H.H.; Remuzzi, G.; Snapinn, S.M.; Zhang, Z.; Shahinfar, S. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N. Engl. J. Med., 2001, 345, 861.
20. Lewis, E.J.; Hunsicker, L.G.; Clarke, W.R.; Berl, T.; Pohl, M.A.; Lewis, J.B.; Ritz, E.; Atkins, R.C.; Rohde, R.; Raz, I. Renoprotec-tive effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N. Engl. J. Med., 2001, 345, 851.
21. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the antihypertensive and lipidlowering treatment to prevent heart attack trial (ALLHAT). JAMA, 2002, 288, 2981.
22. Dahlof, B.; Sever, P.S.; Poulter, N.R.; Wedel, H.; Beevers, D.G.; Caulfield, M.; Collins, R.; Kjeldsen, S.E.; Kristinsson, A.; McInnes, G.T.; Mehlsen, J.; Nieminen, M.; O'Brien, E.; Ostergren, J. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the angloscandinavian cardiac outcomes trial-blood pressure lowering arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet, 2005, 366, 895.
23. Coca, A. Blood pressure control among treated hypertensive patients by primary care in spain. the 2003 controlpres study. Hypertension, 2005, 22, 5.
24. Nesbitt, S.D. Antihypertensive combination therapy: optimizing blood pressure control and cardiovascular risk reduction. J. Clin. Hypertens. (Greenwich), 2007, 9(11Suppl. 4), 26.
25. Escobar, C.; Barrios, V. Combined therapy in the treatment of hypertension. Fundam. Clin. Pharmacol., 2009 [Epub ahead of print].
26. Tigerstedt, R.; Bergman, P.G. Niere Und Kreislauf. Scand. Arch. Physiol., 1898, 8, 223.
27. Schmieder, R.E.; Hilgers, K.F.; Schlaich, M.P.; Schmidt, B.M. Renin-angiotensin system and cardiovascular risk. Lancet, 2007, 369, 1208.
28. Barrios, V.; Escobar, C.; Calderon, A. Candesartan: from left ventricular hypertrophy to heart failure, a global approach. Expert Rev. Cardiovasc. Ther., 2007, 5,825.
29. Torp-Pedersen, C.; Kober, L. TRACE Study Group. Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. Lancet, 1999, 354, 9.
30. Swedberg, K.; Pfeffer, M.; Granger, C.; Held, P.; McMurray, J.; Ohlin, G.; Olofsson, B.; Ostergren, J.; Yusuf, S. Candesartan in heart failure-assessment of reduction in mortality and morbidity (CHARM): rationale and design. J. Card. Fail., 1999, 5, 276.
31. Dzau, V.J.; Bernstein, K.; Celermajer, D.; Cohen, J.; Dahlöf, B.; Deanfield, J.; Diez, J.; Drexler, H.; Ferrari, R.; Van, Gilst, W.; Hansson, L.; Hornig, B.; Husain, A.; Johnston, C.; Lazar, H.; Lonn, E.; Lüscher, T.; Mancini, J.; Mimran, A.; Pepine, C.; Rabelink, T.; Remme, W.; Ruilope, L.; Ruzicka, M.; Schunkert, H.; Swedberg, K.; Unger, T.; Vaughan, D.; Weber, M. Pathophysiologic and therapeutic importance of tissue ACE: a consensus report. Cardiovasc. Drugs Ther., 2002, 16, 149.
32. Lindholm, L.H.; Ibsen, H.; Dahlof, B.; Devereux, R.B.; Beevers, G.; de Faire, U.; Fyhrquist, F.; Julius, S.; Kjeldsen, S.E.; Kristiansson, K.; Lederballe-Pedersen, O.; Nieminen, M.S.; Omvik, P.; Oparil, S.; Wedel, H.; Aurup, P.; Edelman, J.; Snapinn, S. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet, 2002, 359, 1004.
33. Jorde, Up.; Ennezat, Pv,; Lisker, J.; Suryadevara, V.; Infeld, J.; Cukon, S.; Hammer, A.; Sonnenblick, E.H.; Le Jemtel, T.H. Maximally recommended doses of angiotensin-converting enzyme (ACE) inhibitors do not completely prevent ACE mediated formation of angiotensin II in chronic heart failure. Circulation, 2000, 10, 844.
34. Timmermans, P.B.; Wong, P.C.; Chiu, A.T.; Herblin, W.F.; Benfield, P.; Carini, D.J.; Lee, R.J.; Wexler, R.R.; Saye, J.A.; Smith, R.D. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol. Rev., 1993, 45, 205.
35. Goodfriend, T.L.; Elliott, M.E.; Catt, K.J. Angiotensin receptors and their antagonists. N. Engl. J. Med., 1996, 334, 1649.
36. Ford, W.R.; Clanachan, A.S.; Jugdutt, B.I. Opposite effects of angiotensin AT1 and AT2 receptor antagonists on recovery of mechanical function after ischemia-reperfusion in isolated working rat hearts. Circulation, 1996, 94, 3087.
37. Yusuf, S.; Teo, K.K.; Pogue, J.; Dyal, L.; Copland, I.; Schumacher, H.; Dagenais, G.; Sleight, P.; Anderson, C. ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N. Engl. J. Med., 2008, 358, 1547.
38. Berl, T. Review: renal protection by inhibition of the reninangiotensin-aldosterone system. J. Renin. Angiotensin. Aldosterone. Syst., 2009, 10, 1.
39. Sever, P.S.; Gradman, A.H.; Azizi, M. Managing cardiovascular and renal risk: the potential of direct renin inhibition. J. Renin. Angiotensin. Aldosterone. Syst., 2009, 10, 65.
40. Yusuf, S.; Sleight, P.; Pogue, J.; Bosch, J.; Davies, R.; Dagenais, G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators. N. Engl. J. Med., 2000, 342, 145.
41. Azizi, M.; Menard, J.; Bissery, A.; Guyenne, T.T.; Bura-Riviére, A.; Vaidyanathan, S.; Camisasca, R.P. Pharmacologic demonstration of the synergistic effects of a combination of the renin inhibitor aliskiren and the AT1 receptor antagonist valsartan on the angiotensin II-renin feedback interruption. J. Am. Soc. Nephrol., 2004, 15, 3126.
42. Weber, M.A.; Giles, T.D. Inhibiting the renin-angiotensin system to prevent cardiovascular diseases: do we need a more comprehensive strategy? Rev. Cardiovasc. Med., 2006, 7, 45.
43. Baldonicini, R.; Desideri, G.; Bellini, C.; Valenti, M.; De Mattia, G.; Santucci, A.; Ferri, C. High plasma renin activity is combined with elevated urinary albumin excretion in essential hypertensive patients. Kidney Int., 1999, 56, 1499.
44. Maibaum, J.; Feldman, D.L. Renin inhibitors as novel treatments for cardiovascular disease. Expert Opin. Ther. Pat., 2003, 13, 589.
45. Bergset, J.; Storozynsky, E.; Bisognano, J.D. Renin inhibition for hypertension: selecting the right role for a new class of drug. Am. J. Ther., 2009, May 15. [Epub ahead of print].
46. Azizi, M.; Webb, R.; Nussberger, J.; Hollenberg, N.K. Renin inhibition with aliskiren: where are we now, and where are we going? J. Hypertens., 2006, 24, 243.
47. Buczko, W.; Hermanowicz, J.M. Pharmacokinetics and pharmacodynamics of aliskiren, an oral direct renin inhibitor. Pharmacol. Rep., 2008, 60, 623.
48. Abassi, Z.; Winaver, J.; Feuerstein, G.Z. The biochemical pharmacology of renin inhibitors: implications for translational medicine in hypertension, diabetic nephropathy and heart failure Expectations and reality. Biochem. Pharmacol., 2009, 78, 933.
49. Stanton, A. Potential of renin inhibition in cardiovascular disease. J. Renin. Angiotensin. Aldosterone. Syst., 2003, 4, 6.
50. Bruckner, A. Aliskiren (Tekturna®) Novartis. Drug Monograph. Creighton University Drug Information Center. Novartis Pharmaceuticals Corporation. East Hanover: NJ 2007.
51. Cada, D.J.; Levien, T.; Baker, D.E. Aliskiren. Hosp. Pharm., 2007, 42, 737.
52. Vaidyanathan, S.; Jermany, J.; Yeh, Ch.; Bizot, M.N.; Camisasca, R. Aliskiren, a novel orally effective renin inhibitor, exhibits similar pharmacokinetics and pharmacodynamics in Japanese and Caucasin subjects. Br. J. Clin. Pharmacol., 2006, 62, 690.
53. Vaidyanathan, S.; Reynolds, Ch.; Yet, C.M.; Bizot, M.N.; Dieterich, H.A.; Howard, D.; Dole, W.P. Pharmacokinetics, safety, and tolerability of the novel oral direct renin inhibitor aliskiren in elderly healthy subjects. J. Clin. Pharmacol., 2007, 47, 453.
54. Vaidyanathan, S.; Valencia, J.; Kemp, C.; Zhao, C.; Yeh, C-M.; Bizot, M-N; Denouel, J.; Dieterich, H.A.; Dole, W.P. Lack of pharmacokinetic interaction of aliskiren a novel direct renin inhibitor for the treatment of hypertension with the antihypertensive amlopine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthly volunteers. Int. J. Clin. Pract., 2006, 60, 1343.
55. Tecturna (aliskiren) tablets [prescribing information] East Hanover, NJ: Novartis Phamaceuticals Corporation; December 2007. [Accessed December, 2007]. Available from: http:/www.pharma.us.novartis.com/product/pi/pdf/tekturna.pdf
56. Zhao, C.; Vaidynanathan, S.; Yeh, C.M.; Maboudian, N.; Dieterich, H.A. Aliskiren exhibits similar pharmacokinetics in healthy volunteers and patients with type 2 diabetes mellitus. Clin. Pharmacokinet., 2006, 45, 1125.
57. Gradman, A.H.; Pinto, R.; Kad, R. Current concepts: renin inhibition in the treatment of hypertension. Curr. Opin. Pharmacol., 2008, 8, 120.
58. Gradman, A.H.; Schmieder, R.E.; Lins, R.L.; Nussberger, J.; Chiang, Y.; Bedigian, M.P. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo like tolerability in hypertensive patients. Circulation, 2005, 777, 1012.
59. Weir, M.; Bush, C.; Anderson, D.; Zhang, J.; Keefe, D.; Satlin, A. 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.
60. Oh, B.H.; Mitchell, J.; Herron, J.R.; Chung, J.; Khan, M.; Keefe, D.L. Aliskiren an oral renin dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J. Am. Coll. Cardiol., 2007, 49, 1157.
61. Uresin, Y.; Taylor, A.; Kilo, C.; Tschöpe, D.; Santonastaso, M.; Ibram, G.; Fang, H.; Satlin, A. 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.
62. Andersen, K.; Weinberger, M.H.; Egan, B.; Constance, C.M.; Ali, M.A.; Jin, J.; Keefe, D.L. Comparative efficacy and safety of aliskiren, an oral direct renin inhibitor, and ramipril in hypertension: a 6-month, randomized, double-blind trial. J. Hypertens., 2008, 26, 589.
63. Villamil, A.; Chrysant, S.; Calhoun, D.; Schober, B.; Hsu, H.; Matrisciano-Dimichino, L.; Zhang, J. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J. Hypertens., 2007, 25, 217.
64. Schmieder, R.E.; Philipp, T.; Guerediaga, J.; Gorostidi, M.; Smith, B.; Weissbach, N.; Maboudian, M.; Botha, J.; van Ingen, H. Long term antihypertensive efficacy and safety of the oral direct renin inhibitor aliskiren: a 12-month randomized, double-blind comparator trial with hydrochlorothiazide. Circulation, 2009, 119, 417.
65. Schmieder, R.E.; Philipp, T.; Guerediaga, J.; Gorostidi, M.; Bush, C.; Keefe, D.L. Aliskiren-based therapy lowers blood pressure more effectively than hydrochlorothiazide-based therapy in obese patients with hypertension: sub-analysis of a 52-week, randomized, double-blind trial. J. Hypertens., 2009, 27, 1493.
66. Oparil, S.; Yarows, S.A.; Patel, S.; Fang, H. Zhang, J.; Satlin, A. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet, 2007, 370, 221.
67. Pool, J.L.; Schmieder, R.E.; Azizi, M.; Aldigier, J.C.; Januszewicz, A.; Zidek, W.; Chiang, Y.; Satlin, A. Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan. Am. J. Hypertens., 2007, 20, 11.
68. Parving, H.H.; Persson, F.; Lewis, J.B.; Lewis, E.J.; Hollenberg, N.K.; AVOID study investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N. Engl. J. Med., 2008, 358, 2433.
69. Drummond, W.; Munger, M.A.; Essop, M.R.; Maboudian, M.; Khan, M.; Keefe, D.L. Antihypertensive 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.
70. Littlejohn, T.W., 3rd.; Trenkwalder, P.; Hollanders, G.; Zhao, Y.; Liao, W. Long-term safety, tolerability and efficacy of combination therapy with aliskiren and amlodipine in patients with hypertension. Curr. Med. Res. Opin., 2009, 25, 951.
71. Beckett, N.S.; Peters, R.; Fletcher, A.E.; Staessen, J.A.; Liu, L.; Dumitrascu, D.; Stoyanovsky, V.; Antikainen, R.L.; Nikitin, Y.; Anderson, C.; Belhani, A.; Forette, F.; Rajkumar, C.; Thijs, L.; Banya, W., Bulpitt, C.J.; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N. Engl. J. Med., 2008, 358, 1887.
72. Duprez, D.A.; Davis, P.; Botha, J. The AGELESS study: the effect of aliskiren vs ramipril alone or in combination with hydrochlorothiazide and amlodipine in patients ≥65 years of age with systolic hypertension. Circulation, 2008, 118, S886-S887 (A4423).
73. Solomon, S.D.; Appelbaum, E.; Manning, W.J.; Verma, A.; Berglund, T.; Lukashevich, V.; Cherif, Papst, C.; Smith, B.A.; Dahlöf, B.; Aliskiren in left ventricular hypertrophy (ALLAY) trial investigators. 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, 530.
74. Cleland, J.G.; Abdellah, A.T.; Khaleva, O.; Coletta, A.P.; Clark, A.L. Clinical trials update from the European Society of Cardiology Congress 2007: 3CPO, ALOFT, PROSPECT and statins for heart failure. Eur. J. Heart Fail., 2007, 9, 1070.
75. Mazon, P.; Gonzalez, J.R. Aliskiren: the future of treatment for cardiovascular and renal disease. The ASPIRE HIGHER program and the AVOID, ALOFT and ALLAY studies. Rev. Esp. Cardiol. Suppl. 2009, 9, 60A-73A.
76. Nussberger, J.; Aubert, J.F.; Bouzourene, K.; Pellegrin, M.; Hayoz, D.; Mazzolai, L. Renin inhibition by aliskiren prevents atherosclerosis progression: comparison with irbesartan, atenolol, and amlodipine. Hypertension, 2008, 51, 1306.
77. Parving, H.H.; Brenner, B.M.; McMurray, J.J.; de Zeeuw, D.; Haffner, S.M.; Solomon, S.D.; Chaturvedi, N.; Ghadanfar, M.; Weissbach, N.; Xiang, Z.; Armbrecht, J.; Pfeffer, M.A. Aliskiren trial in type 2 diabetes using cardio-renal endpoints (ALTITUDE): rationale and study design. Nephrol. Dial. Transplant., 2009, 24, 1663.
78. Peitz, G.J.; Malesker, M.A.; Sojka, S.G. Aliskiren-induced QT interval prolongation. South. Med. J., 2009, 102, 411.