ACE inhibitor therapy for heart failure with mildly reduced ejection fraction (HFmrEF)
Lisinopril (an angiotensin-converting enzyme inhibitor [ACEi]) is recommended as part of guideline-directed medical therapy for symptomatic HF with mildly reduced ejection fraction (LVEF 41% to 49%). [1] For HFmrEF, ACEi therapy is a Class IIb recommendation in the 2022 AHA/ACC/HFSA guideline. [1]
Medication Selection Algorithm
ACE inhibitors (including lisinopril) are included among the recommended disease-modifying medication options for HFmrEF. [1]
- ACE inhibitors (including lisinopril) [1]
- Angiotensin receptor blockers (ARBs) [1]
- Angiotensin receptor neprilysin inhibitors (ARNIs) [1]
Key Evidence Supporting This Recommendation
Guideline recommendations for HFmrEF reflect evidence-based benefit across the spectrum of ejection fraction, with lower certainty than for HFrEF therapies. [1] No quantified lisinopril-specific effect size for the 40% to 49% EF range is provided in the cited guideline summary statements. [1]
Monotherapy vs Combination Therapy
ACEi therapy is used as part of a combination regimen for HFmrEF rather than as a standalone therapy. [1] SGLT2 inhibitors are recommended with a higher class (Class IIa) for HFmrEF, and mineralocorticoid receptor antagonists (MRAs) are also Class IIb for HFmrEF, supporting multi-drug treatment strategies. [1]
Important Clarifications or Nuances
HFmrEF is defined as symptomatic heart failure with LVEF 41% to 49% in the referenced guidance document. [1] ACEi is listed alongside ARB and ARNI rather than as an isolated recommendation. [1]
Initiation Thresholds or Indications
ACEi therapy is indicated for symptomatic HFmrEF with LVEF 41% to 49% in the 2022 AHA/ACC/HFSA guideline. [1]
Common Pitfalls to Avoid
Renal function and serum potassium should be monitored when initiating or up-titrating renin-angiotensin system inhibitors. [2] If ACEi is not tolerated, guideline-based alternative options include ARB-based regimens in HFmrEF. [2]
Target Blood Pressure
Targets for blood pressure are not specified for HFmrEF ACEi selection in the cited guideline excerpts. [1] Renal function and electrolyte monitoring are specified to support safe ACEi use. [2]
Direct Answer for LVEF 40–49%
For the EF range 40–49%, lisinopril is recommended for the HFmrEF portion of the range (LVEF 41% to 49%) as a Class IIb therapy in the 2022 AHA/ACC/HFSA guideline. [1] For mildly reduced ejection fraction (commonly corresponding to HFmrEF 41% to 49%), NICE recommends considering ACE inhibitors. [2]