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Published on: February 18, 2022

Clinical Consequences of Withdrawing Guideline-Directed Medical Therapy in Heart Failure with Improved Ejection

Tooba Rehman1, Muhammad Aqib Faizan1, Muhammad Waqas1

  • 1. Gomal Medical College, Khyber Medical University, KPK, Pakistan.

Critical Pathways in Cardiology
|July 23, 2026
PubMed

Insights

Stopping Guideline Directed Medical Therapy (GDMT) in heart failure with improved ejection fraction (HFimpEF) patients increases relapse risk. Discontinuing renin-angiotensin-aldosterone system inhibitors (RAASi) significantly raises mortality risk, mandating lifelong GDMT.

Area of Science:

  • Cardiology
  • Pharmacology
  • Clinical Medicine

Background:

  • Heart failure with reduced ejection fraction (HFrEF) and heart failure with improved ejection fraction (HFimpEF) are dynamic conditions influenced by pharmacologic therapy.
  • Guideline Directed Medical Therapy (GDMT) is crucial for HFrEF, but its necessity and safety in HFimpEF post-recovery are unclear.

Purpose of the Study:

  • To systematically review and meta-analyze studies on the effects of withdrawing GDMT in patients with HFimpEF.
  • To assess the risks associated with discontinuing GDMT, particularly specific drug classes, in recovered HFimpEF patients.

Main Methods:

  • Systematic review and meta-analysis of randomized controlled trials and observational studies.
  • Included five studies with a total of 4,773 patients comparing GDMT withdrawal versus continuation in HFimpEF.

Main Results:

  • Withdrawal of comprehensive GDMT (≥2 drug classes) significantly increased the risk of adverse cardiac remodeling relapse (RR = 9.35, p = 0.02).
  • Stopping renin-angiotensin-aldosterone system inhibitors (RAASi) was linked to a higher risk of all-cause mortality (RR = 1.50, p = 0.01).
  • Withdrawal of beta-blockers alone did not significantly affect mortality.

Conclusions:

  • Recovery in HFimpEF is often dependent on continued GDMT, with withdrawal posing substantial risks of relapse and death.
  • Lifelong GDMT is recommended for most HFimpEF patients due to continued vulnerability, essential for preventing relapse and improving survival.
  • Selective GDMT withdrawal may be considered only in highly selected patients under strict monitoring pending reliable predictors of durable recovery.

Keywords:
drug withdrawalguideline-directed medical therapyheart failureimproved ejection fractionmortalityrelapseremodelling

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