• 1
    Packer M. Pathophysiology of chronic heart failure. Lancet 1992; 340: 8892.
  • 2
    Krum H. Role of renin in heart failure and therapeutic potential of direct renin inhibition. J Renin Angiotensin Aldosterone Syst 2008; 9: 177180.
  • 3
    SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293302.
  • 4
    SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 1992; 327: 685691.
  • 5
    Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345: 16671675.
  • 6
    McMurray JJ, Ostergren J, Swedberg K, et al; CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003; 362: 767771.
  • 7
    Konstam MA, Neaton JD, Dickstein K, et al; HEAAL Investigators. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet 2009; 374: 18401848.
  • 8
    Latini R, Masson S, Anand I, et al; Val-HeFT Investigators. The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT. Eur Heart J 2004; 25: 292299.
  • 9
    Vergaro G, Fontana M, Poletti R, et al. Plasma renin activity is an independent prognostic factor in chronic heart failure. Eur Heart J 2008; 29((suppl):): 393. Abstract.
  • 10
    Hollenberg NK. Direct renin inhibition and the kidney. Nat Rev Nephrol 2010; 6: 4955.
  • 11
    Buczko W, Hermanowicz JM. Pharmacokinetics and pharmacodynamics of aliskiren, an oral direct renin inhibitor. Pharmacol Rep 2008; 60: 623631.
  • 12
    Westermann D, Riad A, Lettau O, et al. Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure. Hypertension 2008; 52: 10681075.
  • 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: 569576.
  • 14
    Connelly KA, Kelly DJ, Kim S, et al. The direct renin inhibitor, aliskiren, improves cardiac function via direct renin inhibition and via renin receptor modulation in a rodent model of diabetic diastolic heart failure. Circulation 2008; 118: S1166Abstract 6248.
  • 15
    McMurray JJ, Pitt B, Latini R, et al; Aliskiren Observation of Heart Failure Treatment (ALOFT) Investigators. Effects of the oral direct renin inhibitor aliskiren in patients with symptomatic heart failure. Circ Heart Fail 2008; 1: 1724.
  • 16
    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: 11201127.
  • 17
    Solomon SD, Appelbaum E, Manning WJ, et al; 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: 530537.
  • 18
    Solomon SD. ASPIRE Study results. Paper presented at: American College of Cardiology 59th Scientific Sessions; March 16, 2010; Atlanta, GA.
  • 19
    Adamopoulos C, Ahmed A, Fay R, et al; EPHESUS Investigators. Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial. Eur J Heart Fail 2009; 11: 10991105.
  • 20
    Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Com- bination on Morbi-mortality in Patients With Chronic Heart Failure (ATMOSPHERE). Identifier: NCT00853658. http://www. Accessed May 20, 2010.