In a patient whose echocardiogram has improved from a reduced ejection fraction to a normal ejection fraction, which guideline-directed heart-failure (cardioprotective) medications should be continued and for how long?

Continue All Guideline-Directed Medical Therapy Indefinitely

Patients with heart failure whose ejection fraction has improved from reduced to normal should continue all cardioprotective medications (ACE inhibitors/ARBs/ARNIs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors) indefinitely, as discontinuation significantly increases the risk of relapse, heart failure hospitalization, and death.

The Evidence for Continued Therapy

The 2022 ACC/AHA/HFSA guidelines explicitly recognize "heart failure with improved ejection fraction" (HFimpEF) as a distinct subgroup of HFrEF, not as recovered or cured heart failure 1. This classification acknowledges that ejection fraction improvement is often therapy-dependent and reversible upon medication withdrawal.

Critical Findings on Medication Withdrawal

The most recent meta-analyses provide compelling evidence against stopping therapy:

• Comprehensive GDMT withdrawal (discontinuing ≥2 drug classes) increases relapse risk dramatically (OR 15.37,95% CI 2.75-85.82) 2
• Stopping RAAS inhibitors specifically increases all-cause mortality by 50% (RR=1.50,95% CI 1.09-2.07) 3
• Relapse rates reach 58% in patients who discontinue therapy, particularly in dilated cardiomyopathy 2
• Up to 28.6% of HFimpEF patients experience recurrent HFrEF during follow-up, with discontinuation of GDMT being a major contributor 4

Which Medications to Continue

All four pillars of GDMT must be continued:

1. ACE inhibitors/ARBs/ARNIs - Class I recommendation for indefinite continuation 5, 1. These show the strongest association with maintaining improved EF 6 and preventing mortality when continued 3

2. Beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) - Class I recommendation for indefinite use in patients with prior systolic dysfunction 5, 1. Higher doses correlate with sustained improvement 7

3. Mineralocorticoid receptor antagonists - Class I recommendation for patients who previously had EF <40% with symptoms 5, 1

4. SGLT2 inhibitors - Should be continued based on their proven mortality benefit in HFrEF 8, 1, though specific data in HFimpEF is still emerging

Duration: Lifelong Therapy

There is no safe stopping point. The guidelines and evidence converge on indefinite continuation:

• The 2022 ACC/AHA/HFSA guidelines state that patients with HFimpEF "should continue HFrEF treatment" without specifying an endpoint 1
• The 2016 ESC guidelines recommend ACE inhibitors and beta-blockers "indefinitely" for patients with history of systolic dysfunction 9
• Real-world data shows that EF can decrease after withdrawal even when it has normalized, and this trajectory is not always predictable 1, 4

Clinical Reasoning

The paradigm shift here is understanding that HFimpEF represents medication-dependent recovery, not cure. The underlying structural and molecular abnormalities often persist despite EF normalization 1. Think of it like diabetes control with insulin—stopping therapy because glucose normalizes would be illogical.

Common Pitfalls to Avoid

1. Assuming "normal EF" means "cured" - Cardiac structural abnormalities (chamber dilatation, diastolic dysfunction) typically persist despite EF improvement 1

2. Stopping medications due to tolerability concerns without attempting dose optimization - If side effects occur, adjust doses rather than discontinue entirely. Even lower doses provide some protection 7

3. Discontinuing therapy after device implantation - ICD placement does not replace medical therapy; both are needed

4. Selective withdrawal of "less important" medications - All four pillars work synergistically. Stopping even one class increases risk 3, 4

Special Considerations

Atrial fibrillation-mediated cardiomyopathy may be an exception where some patients maintain function after rhythm control, but this requires careful individualized assessment and close monitoring 2. Even in this subset, the default should be continuation unless compelling reasons exist to stop.

Monitoring strategy: Repeat echocardiography every 6-12 months to detect early relapse 7. The 6-month mark appears to be when LVEF trajectories begin to diverge and predict outcomes 7.

Dose matters: Higher doses of RAAS inhibitors and beta-blockers correlate with sustained improvement 7. Target the doses used in clinical trials (see 8 for specific targets).

Bottom Line Algorithm

1. Confirm HFimpEF diagnosis: Previous LVEF ≤40% now improved to >40%
2. Continue all four GDMT pillars at maximally tolerated doses
3. Never discontinue based solely on EF normalization
4. Monitor with echocardiography every 6-12 months
5. If relapse occurs (EF drops >10% back to ≤40%), this confirms therapy-dependence and reinforces need for lifelong treatment
6. Only consider withdrawal in highly selected cases (e.g., confirmed tachycardia-induced cardiomyopathy with sustained rhythm control) under strict monitoring—but this should be the rare exception, not the rule

The evidence is unequivocal: stopping cardioprotective medications in HFimpEF is harmful 2, 3, 4. Continue therapy indefinitely.