Arnis

ARNIs, or angiotensin receptor-neprilysin inhibitors, are a class of cardiovascular medications that combine an angiotensin receptor blocker with a neprilysin inhibitor. The prototypical ARNI is sacubitril/valsartan, marketed as Entresto. The combination is designed to reduce the effects of the renin-angiotensin system while enhancing natriuretic peptide activity.

Mechanism of action involves two complementary effects. The ARB component (valsartan) blocks the angiotensin II receptor, reducing vasoconstriction, aldosterone secretion, and cardiac remodeling. The neprilysin inhibitor (sacubitril) prevents breakdown of natriuretic peptides, bradykinin, and other vasoactive peptides, promoting vasodilation, natriuresis, diuresis, and anti-remodeling. The net result is lower blood pressure and reduced strain on the heart.

Indications and evidence primarily concern heart failure with reduced ejection fraction (HFrEF). In clinical trials, sacubitril/valsartan reduced cardiovascular death and heart failure hospitalizations compared with an ACE inhibitor. It is commonly used to replace an ACE inhibitor or, less often, an ARB in eligible patients. It is not generally approved for heart failure with preserved ejection fraction (HFpEF), where evidence of benefit is limited.

Safety and usage considerations include a risk of hypotension, hyperkalemia, and renal function changes. Angioedema risk is increased, especially in patients with prior ACE inhibitor–related angioedema. A washout period is recommended when switching from an ACE inhibitor to an ARNI to reduce angioedema risk. Contraindications include a history of angioedema related to previous ACE inhibitors or ARBs and use with aliskiren in diabetes; pregnancy is advised against.

Documentation and ongoing monitoring should address blood pressure, electrolytes, and kidney function.