Can sacubitril and valsartan (Entresto) be restarted in patients with Non-ST-Elevation Myocardial Infarction (NSTEMI) or Congestive Heart Failure (CHF) after being stopped in the hospital?

Restarting Sacubitril/Valsartan After NSTEMI/CHF Hospitalization

Yes, you can and should restart sacubitril/valsartan in hemodynamically stable patients after NSTEMI or acute decompensated heart failure, ideally before hospital discharge. The evidence strongly supports in-hospital reinitiation once patients are stabilized, with demonstrated safety and superior outcomes compared to delaying therapy. 1

When to Restart: Timing and Stability Criteria

Restart sacubitril/valsartan once the patient is hemodynamically stable, which means:

• At least 24 hours after initial presentation 2
• Resolution of acute heart failure symptoms (no longer requiring IV diuretics or vasopressors) 1
• Systolic blood pressure stable (ideally >100 mmHg, though lower pressures may be acceptable if asymptomatic) 1, 3
• No ongoing signs of cardiogenic shock or hypoperfusion 1

The PIONEER-HF trial established that in-hospital initiation is both feasible and beneficial in patients stabilized from acute decompensated heart failure, showing greater NT-proBNP reduction and lower rates of cardiovascular death or rehospitalization compared to enalapril. 1, 2

Specific Context: Post-NSTEMI Considerations

For NSTEMI patients specifically, the evidence is more nuanced:

• The PARADISE-MI trial showed sacubitril/valsartan did not significantly reduce the primary outcome (cardiovascular death, HF hospitalization, or outpatient HF) when started within 7 days of MI in patients with newly depressed EF <40% or signs of heart failure (HR: 0.90; 95% CI: 0.78-1.04; P=0.17). 1
• However, there was a nominal reduction in secondary endpoints (cardiovascular death and total hospitalizations for HF, MI, or stroke: HR: 0.84; 95% CI: 0.70-1.00; P=0.045). 1
• Current guidelines state that "the efficacy of ARNi in patients with LV dysfunction and HF in the early post-MI period remains uncertain." 1

Despite this uncertainty, if the patient has established HFrEF (not just acute MI-related dysfunction), sacubitril/valsartan remains indicated and should be restarted based on their chronic heart failure diagnosis. 1

Dosing Strategy for Reinitiation

Start at the appropriate dose based on prior exposure and clinical factors: 3, 4

• 49/51 mg twice daily if previously on high-dose ACE inhibitor or ARB 3
• 24/26 mg twice daily for:
  • Low/medium-dose prior ACE inhibitor or ARB exposure 3
  • Age ≥75 years 3
  • Severe renal impairment (eGFR <30 mL/min/1.73m²) 3
  • Moderate hepatic impairment 3
  • Borderline blood pressure (systolic 90-100 mmHg) 1, 3

Titrate to target dose of 97/103 mg twice daily every 2-4 weeks as tolerated. 3, 4

Critical Safety Requirements

Mandatory 36-hour washout if switching from an ACE inhibitor to avoid angioedema risk. 1, 3, 4 This is an FDA requirement and absolute contraindication to concurrent use. 4

Monitor for hypotension, which occurred in up to 25% of PIONEER-HF patients: 1

• Ensure patient is not volume-depleted before initiation 1, 3
• Consider empirically reducing loop diuretic doses in noncongested patients to mitigate hypotensive effects 1
• Asymptomatic hypotension does NOT require dose reduction - patient education is essential 3
• Only reduce dose for symptomatic hypotension with dizziness, lightheadedness, or syncope 1, 3

Other monitoring parameters: 1

• Renal function (creatinine, eGFR) 1
• Serum potassium (hyperkalemia risk, though lower than with ACE inhibitors) 1
• Angioedema (comparable incidence to ACE inhibitors) 1

Common Pitfalls to Avoid

Do not permanently discontinue or reduce dose for: 3

• Asymptomatic hypotension (systolic BP 85-100 mmHg without symptoms) 3
• Mild, transient creatinine elevations that stabilize 3
• Mild hyperkalemia that can be managed with dietary modification or potassium binders 3

Do not delay initiation until after discharge - the TRANSITION trial showed similar safety whether started before or after discharge, but in-hospital initiation ensures medication is actually started and allows for monitoring during titration. 1

Do not fail to uptitrate to target dose - approximately 50% of patients can achieve target dose within 10 weeks, and higher doses provide greater mortality benefit. 1, 3, 5

Algorithm for Decision-Making

1. Assess hemodynamic stability (>24 hours from presentation, off IV vasoactive medications, stable blood pressure) 2
2. Verify no contraindications (history of angioedema, concurrent ACE inhibitor use within 36 hours, pregnancy) 1, 4
3. Check baseline labs (creatinine, potassium, blood pressure) 1
4. Optimize volume status (reduce diuretics if not congested and BP borderline) 1, 3
5. Initiate at appropriate starting dose (24/26 or 49/51 mg twice daily based on criteria above) 3, 4
6. Monitor closely for first 1-2 weeks (BP, symptoms, labs) 1, 2
7. Titrate every 2-4 weeks to target dose as tolerated 3, 4

The weight of evidence favors restarting sacubitril/valsartan before discharge in stabilized patients with HFrEF, even in the post-NSTEMI setting, given the established mortality benefit in chronic HFrEF and the safety demonstrated in acute decompensated heart failure. 1, 2, 6