United Kingdom Heart and Renal Protection-III - UK HARP-III

Contribution To Literature:

The UK HARP-III trial showed that sacubitril/valsartan has similar effects on kidney function and albuminuria compared with irbesartan.


The goal of the trial was to evaluate sacubitril/valsartan compared with irbesartan among patients with chronic kidney disease.

Study Design

  • Randomized
  • Parallel
  • Stratified
  • Blinded

Eligible patients were randomized to sacubitril/valsartan (n = 207) versus irbesartan (n = 207).

Inclusion criteria:

  • Estimated glomerular filtration rate (eGFR) 45 to <60 ml/min/1.73 m2 and a urine albumin:creatinine ratio >20 mg/mmol (177 mg/g), or
  • eGFR 20 to <45 ml/min/1.73 m2 (regardless of urine albumin:creatinine ratio)
  • Total number of enrollees: 414
  • Duration of follow-up: 12 months
  • Mean patient age: 62 years
  • Percentage female: 29%
  • Percentage with diabetes: 39%

Principal Findings:

The primary outcome, eGFR at 12 months, was 29.8 ml/min/1.73 m2 in the sacubitril/valsartan group compared with 29.9 ml/min/1.73 m2 in the irbesartan group (p = 0.86).

Secondary outcomes:

  • Urine albumin:creatinine ratio at 12 months: 16.4 mg/mmol in the sacubitril/valsartan group vs. 17.6 mg/mmol in the irbesartan group (p = 0.08)
  • Systolic blood pressure at 12 months: 128 mm Hg in the sacubitril/valsartan group vs. 133 mg/mmol in the irbesartan group (p < 0.001)


Among patients with chronic kidney disease, sacubitril/valsartan was equally effective at preserving renal function or reducing albuminuria compared with irbesartan. Sacubitril/valsartan was associated with improved blood pressure at 12 months.


Haynes R, Judge PK, Staplin N, et al., on behalf of the UK HARP-III Collaborative Group. Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease: A Randomized Double-Blind Trial. Circulation 2018;Jul 12:[Epub ahead of print].

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Heart Failure and Cardiac Biomarkers

Keywords: Albuminuria, Biological Markers, Blood Pressure, Creatinine, Glomerular Filtration Rate, Kidney Failure, Chronic, Metabolic Syndrome X, Neprilysin, Primary Prevention, Receptors, Angiotensin, Renal Insufficiency, Chronic

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