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Neprilysin is the main enzyme responsible for degrading natriuretic peptides (ANP, BNP and CNP) and other vasodilatory peptides. Sacubitril/valsartan is a angiotensin receptor-nepilysin inhibitor which has two actions: one half of the drug is an ARB (valsartan) and the other half of the drug is a neprilysin inhibitor (sacubitril) The drug was shown to be superior to enalapril (an ACE inhibitor) in people with heart failure and animal data suggested it may also reduce renal progression, but no such human data existed.

The UK HARP-III (UK Heart and Renal Protection-III) was a randomised double-blind trial which compared sacubitril/valsartan with irbesartan (an ARB) in 414 participants with chronic kidney disease (estimated glomerular filtration rate [GFR] 20 to 60 mL/min/1.73 m2).

The trial tested whether sacubitril/valsartan reduced the rate of decline in kidney function (determined by measured GFR) at 12 months, compared with current standard treatment (irbesartan).

UK HARP-III showed over 12 months, sacubitril/valsartan had similar effects on kidney function and albuminuria (protein leak in urine) to irbesartan, in a wide range of patients with CKD. However, compared with irbesartan, sacubitril/valsartan had greater blood pressure lowering effects and reduced biomarkers of cardiac disease in people with chronic kidney disease. The tolerability and safety profiles of the 2 treatments were similar. 

Full trial results 

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