Guideline-Directed Medical Therapy Should NOT Be Withdrawn in Heart Failure with Improved Ejection Fraction
In patients with heart failure with improved ejection fraction (HFimpEF), all four pillars of GDMT (ARNI/ACE inhibitor/ARB, beta-blockers, MRAs, and SGLT2 inhibitors) should be continued indefinitely to prevent relapse of heart failure and left ventricular dysfunction, even when patients become asymptomatic. 1
The Evidence Against Withdrawal
The 2022 AHA/ACC/HFSA Guidelines provide a Class 1, Level of Evidence B-R recommendation that GDMT should be continued after LVEF improvement to prevent relapse of HF and LV dysfunction. 1 This recommendation is based on evidence demonstrating that withdrawing heart failure medications in HFimpEF is associated with relapse of cardiomyopathy and reduction in LVEF. 1
Improvement in symptoms, biomarkers, and cardiac function post-treatment does not signify complete and persistent recovery—it indicates remission, necessitating the continuation of treatment. 1
Definition and Classification
Patients with HFimpEF are defined as those with previous HFrEF (LVEF <40%) who now have an LVEF >40%. 1 These patients should be reclassified as HFimpEF but continue to receive the same comprehensive GDMT regimen used for HFrEF. 1
All Four Pillars Must Continue
The four foundational medication classes that must be maintained include:
- ARNI (preferred) or ACE inhibitor/ARB: These provide mortality reduction and should not be discontinued. 2
- Evidence-based beta-blockers (carvedilol, metoprolol succinate, or bisoprolol): These reduce mortality by at least 20% and decrease sudden cardiac death. 2
- Mineralocorticoid receptor antagonists (spironolactone or eplerenone): These reduce mortality and hospitalization in patients with prior HFrEF. 2
- SGLT2 inhibitors: These reduce HF hospitalizations and cardiovascular mortality and should be continued. 1
Clinical Pitfalls to Avoid
A common error is assuming that normalization of LVEF means the patient is "cured" and can discontinue medications. 1 The evidence clearly demonstrates that:
- Discontinuation leads to relapse: Withdrawing GDMT is associated with recurrent cardiomyopathy and declining LVEF. 1
- Asymptomatic status is not an indication to stop: Even patients who become completely asymptomatic should continue all four pillars. 1
- De-escalation after improvement increases mortality risk: Studies show that de-escalation or discontinuation of GDMT after clinical improvement is associated with significantly increased risk of all-cause mortality. 3
Monitoring Strategy
Rather than withdrawing medications, the focus should be on:
- Serial reassessment: Continue monitoring LVEF, symptoms, labs, and health status while maintaining GDMT. 1
- Dose optimization: Ensure patients remain on target or maximally tolerated doses of all four pillars. 1
- Patient education: Emphasize that continued medication adherence is essential to maintain their improved status. 4
The 2024 ACC/AHA performance measures specifically include continuation of GDMT in HFimpEF as a quality metric, reinforcing that this is the standard of care. 1