Sacubitril Valsartan Initiation and Switching

Sacubitril valsartan combines an angiotensin receptor blocker with neprilysin inhibition and is used in symptomatic heart failure with reduced ejection fraction, with an ejection fraction of 40% or under, in place of an ACE inhibitor or angiotensin receptor blocker. It is also used de novo in new or acutely decompensated heart failure once stable. Starting requires systolic pressure of 100 mmHg or over, potassium under 5.0 mmol/L and no history of angioedema.

Contraindications. Angioedema history, pregnancy, severe hepatic impairment (Child-Pugh C), concomitant ACE inhibitor, and aliskiren in diabetes.

Ancestry. Angioedema is more frequent in people of African ancestry.

Start dose. 24/26 mg orally twice daily if the person is ACE inhibitor or angiotensin receptor blocker naive or on low doses (under ramipril 5 mg daily equivalent), has eGFR under 30 mL/min/1.73 m2, has moderate hepatic impairment (Child-Pugh B), has systolic pressure of 100 to 110 mmHg, or is aged 75 or over. Otherwise 49/51 mg twice daily.

Titration. Double the dose every 2 to 4 weeks to the target of 97/103 mg twice daily, as pressure, potassium and creatinine allow.

Switching from an ACE inhibitor. Stop the ACE inhibitor and wait 36 hours before the first dose. Never give both, since this risks angioedema.

Switching from an angiotensin receptor blocker. Start at the next scheduled dose with no washout.

Switching back to an ACE inhibitor. Wait 36 hours after the last dose.

Special groups. In pregnancy and breastfeeding avoid. In older adults start at the lower dose. In creatinine clearance under 30 mL/min use 24/26 mg twice daily and titrate slowly. In East Africa, cost often limits access, and an ACE inhibitor remains an effective base.

Monitoring. Pressure, potassium and creatinine at 1 to 2 weeks after starting and after each increase, then every 3 to 6 months.

Natriuretic peptides. Use NT-proBNP, since BNP rises on this drug.

Hypotension. Reduce the diuretic if the person is euvolaemic, separate other vasodilators, and hold the titration. Reduce the sacubitril valsartan dose last.

Hyperkalaemia. Halve the dose for potassium of 5.5 to 5.9 mmol/L and stop at 6.0 mmol/L or over.

Stopping. Stop permanently for angioedema. Stop temporarily during acute illness with poor intake.

Common errors. Missing the 36 hour washout, starting at the high dose in ACE inhibitor naive people, and measuring BNP rather than NT-proBNP.

Referral and escalation. Refer for symptomatic hypotension that does not settle, hyperkalaemia, a creatinine rise over 30%, or angioedema with airway involvement.