Timing of Sacubitril/Valsartan Initiation After Acute Myocardial Infarction
Sacubitril/valsartan can be initiated as early as 7 days after an acute myocardial infarction in hemodynamically stable patients with reduced ejection fraction, once acute heart failure has been stabilized. 1
Evidence-Based Recommendations
The timing of sacubitril/valsartan initiation after MI depends on several key factors:
Clinical Trial Evidence
- The PARADISE-MI trial specifically examined sacubitril/valsartan in patients with recent MI (within 7 days) and newly depressed EF <40% and/or signs of acute heart failure 1
- While PARADISE-MI did not show a significant reduction in the primary outcome compared to ramipril, it demonstrated safety of early initiation and a nominal reduction in the secondary endpoint of cardiovascular death and total hospitalizations 1, 2
Hemodynamic Stability Considerations
- Initiation should occur only after the patient is hemodynamically stable 1
- Careful monitoring is essential as sacubitril/valsartan may exert more notable effects on blood pressure than ACEIs/ARBs 1
- Symptomatic hypotension occurred in 28.3% of patients treated with sacubitril/valsartan compared to 21.9% with ACE inhibitors in post-MI patients 2
Practical Approach to Initiation
Step 1: Assess Patient Eligibility (Day 1-7 post-MI)
- Confirm reduced ejection fraction (<40%) via echocardiography 1
- Ensure hemodynamic stability (systolic BP >100 mmHg) 1
- Verify acute heart failure has stabilized 1
Step 2: Consider Prior ACEI/ARB Exposure
- For patients on high-dose ACEI: Start with sacubitril/valsartan 49/51 mg twice daily 1
- For patients on low/medium-dose ACEI or ARB: Start with sacubitril/valsartan 24/26 mg twice daily 1
- For ACEI/ARB-naïve patients: Start with sacubitril/valsartan 24/26 mg twice daily 1
Step 3: Implement Special Precautions
- For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²): Start with lower dose (24/26 mg twice daily) 1
- For elderly patients (≥75 years): Consider starting at lower dose 1
- For patients with borderline blood pressure: Consider empiric reduction of loop diuretic dose 1
Potential Benefits of Early Initiation
Early initiation of sacubitril/valsartan after MI may provide several benefits:
- Improved cardiac function parameters including LVEF and stroke volume 3
- Reduced ventricular remodeling markers 3, 4
- Decreased NT-proBNP, Gal-3, and PIIINP levels 3
- Anti-inflammatory effects and reduced acute systemic inflammatory markers 5
- Potential reduction in scar formation and border zone mass 5
Important Caveats and Precautions
- ACE inhibitors remain first-line therapy in the first week(s) after MI based on established evidence 2
- Avoid initiation in patients with hypotension (systolic BP <100 mmHg) 1
- Do not use in patients with bilateral renal artery stenosis, history of angioedema, or hyperkalemia 1, 6
- Monitor renal function and electrolytes closely when initiating therapy 6
- Consider a 36-hour washout period if switching from an ACE inhibitor to prevent angioedema risk
Follow-up Recommendations
- Assess blood pressure, renal function, and electrolytes within 1-2 weeks after initiation
- Titrate dose gradually over 3-6 weeks to target dose as tolerated 1
- Continue monitoring for hypotension, which is the most common adverse effect 2
- Reassess cardiac function via echocardiography at 3 months to evaluate improvement 6
While the evidence suggests sacubitril/valsartan can be initiated as early as 7 days post-MI, clinical judgment should prioritize hemodynamic stability and careful monitoring for hypotension, especially in high-risk patients.