From the Research
Sacubitril primarily affects the afferent arteriole by inhibiting neprilysin, an enzyme that degrades natriuretic peptides, leading to increased levels of natriuretic peptides, which cause dilation of the afferent arteriole in the kidney, as supported by the most recent study 1.
Mechanism of Action
The inhibition of neprilysin by sacubitril leads to increased levels of natriuretic peptides, which cause dilation of the afferent arteriole in the kidney. When the afferent arteriole dilates, there is increased renal blood flow and glomerular filtration rate, promoting sodium and water excretion.
Clinical Use
Sacubitril is typically used in combination with valsartan (as Entresto) for heart failure treatment, with starting doses of 24/26 mg twice daily, titrated to a target of 97/103 mg twice daily as tolerated.
Comparison with Other Treatments
This afferent arteriolar dilation contrasts with the effects of ACE inhibitors and ARBs, which primarily dilate the efferent arteriole. The dual action of sacubitril/valsartan provides complementary effects on renal hemodynamics, enhancing natriuresis while maintaining glomerular filtration, as shown in a systematic review and meta-analysis 1.
Benefits and Risks
The mechanism explains why sacubitril/valsartan can improve cardiac function while having potentially renoprotective effects in heart failure patients, though careful monitoring of kidney function is still necessary when initiating therapy, as noted in a study on the efficacy and safety of sacubitril/valsartan in heart failure compared to renin-angiotensin-aldosterone system inhibitors 1. Some key points to consider:
- Sacubitril/valsartan has been shown to reduce mortality and hospitalization rates in patients with heart failure with reduced ejection fraction (HFrEF) compared to ACE inhibitors or ARBs, as demonstrated in a systematic review and meta-analysis 1.
- The dual action of sacubitril/valsartan provides complementary effects on renal hemodynamics, enhancing natriuresis while maintaining glomerular filtration, as supported by a study on the effects of sacubitril/valsartan on renal function in patients with chronic kidney disease and heart failure with preserved ejection fraction 2.
- Careful monitoring of kidney function is still necessary when initiating therapy with sacubitril/valsartan, as noted in a review of the clinical benefits and related mechanisms of action of sacubitril/valsartan in heart failure with reduced ejection fraction 3.