Effects of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: a randomised double-blind trial [accepted manuscript]

METHODS: The UK HARP-III trial (United Kingdom Heart and Renal Protection-III), a randomized double-blind trial, included 414 participants with an estimated glomerular filtration rate (GFR) 20 to 60 mL/min/1.73 m2 who were randomly assigned to sacubitril/valsartan 97/103 mg twice daily versus irbesartan 300 mg once daily. The primary outcome was measured GFR at 12 months using ANCOVA with adjustment for each individual’s baseline measured GFR. All analyses were by intention to treat.

[1]  S. Solomon,et al.  Effect of neprilysin inhibition on renal function in patients with type 2 diabetes and chronic heart failure who are receiving target doses of inhibitors of the renin-angiotensin system: a secondary analysis of the PARADIGM-HF trial. , 2018, The lancet. Diabetes & endocrinology.

[2]  H. Moradi,et al.  LCZ696 (Sacubitril/Valsartan), an Angiotensin-Receptor Neprilysin Inhibitor, Attenuates Cardiac Hypertrophy, Fibrosis, and Vasculopathy in a Rat Model of Chronic Kidney Disease. , 2018, Journal of cardiac failure.

[3]  M. Landray,et al.  Prognostic utility of estimated albumin excretion rate in chronic kidney disease: results from the Study of Heart and Renal Protection , 2017, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[4]  A. Fujimura,et al.  Prevention against renal damage in rats with subtotal nephrectomy by sacubitril/valsartan (LCZ696), a dual‐acting angiotensin receptor‐neprilysin inhibitor , 2017, Pharmacology research & perspectives.

[5]  K. Kario,et al.  Effects of Sacubitril/Valsartan Versus Olmesartan on Central Hemodynamics in the Elderly With Systolic Hypertension: The PARAMETER Study , 2017, Hypertension.

[6]  M. Taal,et al.  Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data , 2016, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[7]  S. Solomon,et al.  Combined neprilysin and renin–angiotensin system inhibition in heart failure with reduced ejection fraction: a meta‐analysis , 2016, European journal of heart failure.

[8]  M. Landray,et al.  Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials. , 2016, The lancet. Diabetes & endocrinology.

[9]  E. Hoorn,et al.  Blood pressure-independent renoprotection in diabetic rats treated with AT1 receptor-neprilysin inhibition compared with AT1 receptor blockade alone. , 2016, Clinical science.

[10]  S. Anderson,et al.  Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis , 2016, The Lancet.

[11]  S. Solomon,et al.  Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction , 2015, European journal of heart failure.

[12]  Akshay S. Desai,et al.  Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure , 2015, Circulation.

[13]  S. Solomon,et al.  Elevation in High-Sensitivity Troponin T in Heart Failure and Preserved Ejection Fraction and Influence of Treatment With the Angiotensin Receptor Neprilysin Inhibitor LCZ696 , 2014, Circulation. Heart failure.

[14]  Akshay S. Desai,et al.  Angiotensin-neprilysin inhibition versus enalapril in heart failure. , 2014, The New England journal of medicine.

[15]  K. Kario,et al.  Efficacy and Safety of LCZ696, a First-in-Class Angiotensin Receptor Neprilysin Inhibitor, in Asian Patients With Hypertension: A Randomized, Double-Blind, Placebo-Controlled Study , 2014, Hypertension.

[16]  H. Tighiouart,et al.  Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis , 2013, Canadian Medical Association Journal.

[17]  Chi Pang Wen,et al.  Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention , 2013, The Lancet.

[18]  S. Solomon,et al.  The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial , 2012, The Lancet.

[19]  A. Go,et al.  Associations between kidney function and subclinical cardiac abnormalities in CKD. , 2012, Journal of the American Society of Nephrology : JASN.

[20]  Mark Woodward,et al.  Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts. , 2011, Kidney international.

[21]  M. Woodward,et al.  Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis , 2010, The Lancet.

[22]  L. Ruilope,et al.  Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study , 2010, The Lancet.

[23]  Robert R. Quinn,et al.  Relation between kidney function, proteinuria, and adverse outcomes. , 2010, JAMA.

[24]  George F Borm,et al.  A simple sample size formula for analysis of covariance in randomized clinical trials. , 2007, Journal of clinical epidemiology.

[25]  J. Kaufman,et al.  Age affects outcomes in chronic kidney disease. , 2007, Journal of the American Society of Nephrology : JASN.

[26]  G. Remuzzi,et al.  Vasopeptidase inhibitor restores the balance of vasoactive hormones in progressive nephropathy. , 2004, Kidney international.

[27]  Charles E McCulloch,et al.  Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. , 2004, The New England journal of medicine.

[28]  H. Black,et al.  Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial. , 2004, American journal of hypertension.

[29]  C. Johnston,et al.  Renoprotective effects of vasopeptidase inhibition in an experimental model of diabetic nephropathy , 2003, Diabetologia.

[30]  B. Brenner,et al.  Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy , 2002 .

[31]  B. Brenner,et al.  Vasopeptidase inhibition affords greater renoprotection than angiotensin-converting enzyme inhibition alone. , 2001, Journal of the American Society of Nephrology : JASN.

[32]  B. Brenner,et al.  Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. , 2001, The New England journal of medicine.

[33]  E. Lewis,et al.  Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. , 2001, The New England journal of medicine.

[34]  M. Cooper,et al.  Vasopeptidase inhibition attenuates the progression of renal injury in subtotal nephrectomized rats. , 2001, Kidney international.

[35]  K. Breithaupt-Grögler,et al.  The pharmacological potency of various AT1 antagonists assessed by Schild regression technique in man , 2000, Journal of the renin-angiotensin-aldosterone system : JRAAS.

[36]  Giuseppe Remuzzi,et al.  Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria , 1999, The Lancet.

[37]  R. Foley,et al.  Clinical epidemiology of cardiovascular disease in chronic renal disease. , 1998, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[38]  M. Wilkins,et al.  The natriuretic-peptide family , 1997, The Lancet.

[39]  R. J. Hayes,et al.  Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. , 1995, JAMA.

[40]  David C. Murray,et al.  Clinical and echocardiographic disease in patients starting end-stage renal disease therapy. , 1995, Kidney international.

[41]  R. Bain,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. , 1993, The New England journal of medicine.

[42]  N. Cook,et al.  Estimating the effect of the run-in on the power of the Physicians' Health Study. , 1991, Statistics in medicine.

[43]  J. M. Lang,et al.  The use of a run-in to enhance compliance. , 1990, Statistics in medicine.

[44]  A. D. de Bold,et al.  Atrial natriuretic factor: a hormone produced by the heart. , 1985, Science.

[45]  M. Pike,et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. , 1977, British Journal of Cancer.

[46]  P. Armitage,et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. , 1976, British Journal of Cancer.

[47]  S. Pocock,et al.  Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. , 1975, Biometrics.