How soon after a drop in ejection fraction (EF) following stent placement should Entresto (sacubitril/valsartan) be initiated?

Timing of Entresto Initiation After Post-Stent EF Drop

Entresto (sacubitril/valsartan) should be initiated as soon as the patient is hemodynamically stable after stent placement, typically within 24 hours, once reduced ejection fraction is confirmed and the patient meets criteria for heart failure with reduced ejection fraction (HFrEF).

Immediate Post-Stent Stabilization Period

• The critical window is ensuring hemodynamic stability first, not waiting for an arbitrary time period after stent placement 1, 2.
• Assess blood pressure, renal function (creatinine and potassium), and ensure the patient is not in cardiogenic shock before initiating Entresto 3.
• If the patient has LVEF ≤40% with evidence of heart failure or anterior MI, ACE inhibitor therapy (or ARNI) should begin within the first 24 hours of the acute event 3.

Specific Initiation Strategy

• Start with the lowest dose (24/26 mg twice daily) and titrate upward every 2-4 weeks as tolerated, targeting the maximum tolerated dose 4.
• Do not delay initiation waiting for "optimal" timing—early treatment within the first week provides the most mortality benefit 3.
• If the patient is currently on an ACE inhibitor or ARB, ensure a 36-hour washout period before starting Entresto to avoid angioedema risk 4.

Monitoring Requirements During Initiation

• Check blood pressure, renal function, and potassium levels 1-2 weeks after starting Entresto and after each dose adjustment 2.
• Systolic blood pressure should be >100 mmHg before each dose escalation, though patients may tolerate therapy with lower pressures if asymptomatic 4.
• Monitor for hyperkalemia (K+ >5.5 mEq/L) and worsening renal function (creatinine increase >30% from baseline) 2, 3.

Dose Optimization Timeline

• Target the 97/103 mg twice daily dose within 3-6 months, as this dose demonstrates significantly lower mortality (9.27%) compared to the 24/26 mg dose (29.63%) 5.
• Even the middle dose (49/51 mg twice daily) shows substantial benefit over the lowest dose, with mortality rates of 17.58% vs 29.63% 5.
• Patients who remain on low doses have nearly 3-fold higher mortality risk compared to those reaching target doses 5.

Integration with Post-Stent Antiplatelet Therapy

• Continue dual antiplatelet therapy (aspirin plus ticagrelor/Brilinta) for 12 months post-stent as recommended, which does not contraindicate Entresto initiation 6, 1.
• Add a proton pump inhibitor given the combination of dual antiplatelet therapy and potential for hypotension with Entresto, which increases bleeding risk 2.

Contraindications to Immediate Initiation

• Do not start Entresto if: systolic blood pressure <90 mmHg, serum potassium >5.4 mEq/L, severe renal dysfunction (eGFR <30 mL/min/1.73m²), or history of angioedema 4.
• Cardiogenic shock or severe hypotension requiring vasopressors mandates stabilization before ARNI therapy 3.

Reassessment Strategy

• Repeat echocardiography at 3-6 months to assess ventricular remodeling response to optimized medical therapy including Entresto 1, 2.
• If LVEF remains <35% after 3 months of optimal medical therapy including target-dose Entresto, evaluate for ICD placement for primary prevention of sudden cardiac death 1, 2.

Common Pitfall to Avoid

• The most critical error is delaying Entresto initiation unnecessarily—there is no evidence supporting a mandatory waiting period after stent placement before starting ARNI therapy 3, 4.
• The focus should be on hemodynamic stability and meeting HFrEF criteria, not on an arbitrary time interval from the stent procedure 1, 2.
• Failure to uptitrate to target doses results in substantially worse outcomes, with nearly 3-fold higher mortality at low doses 5.