Entresto in Post-CABG with EF 49%
Direct Recommendation
Do not start Entresto (sacubitril/valsartan) in this patient. An ejection fraction of 49% falls outside the evidence-based indication for sacubitril/valsartan, which requires either HFrEF (EF ≤40%) or, in highly selected cases, HFpEF with specific criteria that your patient does not meet. 1
Rationale Based on EF Classification
Your patient's EF of 49% is classified as heart failure with mildly reduced ejection fraction (HFmrEF), not HFrEF, according to current ACC/AHA definitions that reserve HFrEF designation for EF ≤40%. 2
Sacubitril/valsartan has Class I (strong) evidence only for HFrEF with EF ≤40%, where it reduces cardiovascular death and HF hospitalization by 20% compared to enalapril. 1, 3
For HFpEF (EF ≥45%), sacubitril/valsartan carries only a Class 2b recommendation (may be considered), and even then only in highly selected subgroups—specifically women or patients with EF 45-57% who remain symptomatic despite SGLT2 inhibitor therapy. 1
What This Patient Should Receive Instead
Start an ACE inhibitor immediately (within 24 hours if hemodynamically stable) and continue indefinitely, as this is a Class I, Level A recommendation for all post-CABG patients with any degree of LV dysfunction or heart failure symptoms. 4, 5, 3
Specific ACE Inhibitor Regimen:
Initiate enalapril 2.5-5 mg twice daily, ramipril 2.5 mg daily, or lisinopril 5 mg daily, then uptitrate every 1-2 weeks to target doses (enalapril 10 mg BID, ramipril 10 mg daily, lisinopril 10 mg daily). 3
Add an evidence-based beta-blocker (carvedilol, metoprolol succinate, or bisoprolol) immediately and continue indefinitely—this is mandatory for all post-CABG patients with LV dysfunction. 4, 5, 3
Monitor renal function and potassium 1-2 weeks after starting or uptitrating ACE inhibitor; therapy is contraindicated if creatinine >2.5 mg/dL (men) or >2.0 mg/dL (women), or potassium >5.0 mEq/L. 3
Why Entresto Is Not Appropriate Here
The PARAGON-HF trial, which studied sacubitril/valsartan in HFpEF (EF ≥45%), failed to meet its primary endpoint (rate ratio 0.87; 95% CI 0.75-1.01; p=0.06), showing no significant reduction in cardiovascular death or HF hospitalizations in the overall cohort. 1
Even the subgroup that showed benefit (EF 45-57%) had a median EF of 51%, and your patient at EF 49% sits at the very edge of this range without meeting the additional criteria of female sex or prior SGLT2 inhibitor failure. 1
Sacubitril/valsartan should not be used in patients with EF >60% as no evidence of benefit exists, and your patient's EF of 49% places them in a gray zone where ACE inhibitors have proven mortality benefit but sacubitril/valsartan does not. 1
Post-CABG Safety Considerations
One small observational study (n=30) showed sacubitril/valsartan was tolerated in post-CABG patients with EF <40%, but this does not extend to your patient with EF 49%, and the study had no control group or mortality data. 6
The mandatory 36-hour washout when switching from ACE inhibitor to sacubitril/valsartan creates an unnecessary treatment gap in the acute post-CABG period when continuous RAAS blockade is most critical. 7, 3
Future Consideration for Sacubitril/Valsartan
If your patient's EF drops to ≤40% on repeat echocardiography and they remain symptomatic (NYHA class II-III) despite optimal doses of ACE inhibitor and beta-blocker, then switch to sacubitril/valsartan after a 36-hour ACE inhibitor washout. 3, 7
If EF remains 41-49% but symptoms persist, prioritize adding an SGLT2 inhibitor (dapagliflozin or empagliflozin) and a mineralocorticoid receptor antagonist before considering sacubitril/valsartan, as these have stronger evidence in the mildly reduced EF range. 3
Common Pitfall to Avoid
Do not use sacubitril/valsartan as first-line therapy in post-CABG patients with preserved or mildly reduced EF simply because it is a "newer" drug—ACE inhibitors remain the evidence-based standard with proven mortality benefit in this population, while sacubitril/valsartan lacks such data outside of EF ≤40%. 4, 5, 3