Stopping GDMT after LVEF improvement associated with adverse events
In a retrospective real-world study among HFrEF patients with improved LVEF, withdrawal of RAASis/ARNIs or MRAs, but not beta-blockers, was associated with a higher risk of CV death or HF hospitalization at 1 year.
This summary is based on the publication of Basile C, Lindberg F, Benson L, et al. - Withdrawal of Guideline-Directed Medical Therapy in Patients With Heart Failure and Improved Ejection Fraction. Circulation. 2025 Apr;151(13):931-945. doi: 10.1161/CIRCULATIONAHA.124.072855.
Introduction and methods
Background
In patients with HFrEF, starting GDMT can improve LVEF and subsequently lower the risks of all-cause mortality and hospitalization for HF [1-3]. However, RCT data on whether GDMT can be withdrawn or should be continued in HF patients with improved LVEF are limited [4,5]. For now, clinical guidelines recommend continuing treatment in this population [6,7].
Aim of the study
The study aim was to assess the rates of GDMT withdrawal in HFrEF patients with improved LVEF in a real-world setting, the patient profiles associated with withdrawal, and the relationship between withdrawal and the incidence of adverse events.
Methods
In a retrospective observational study, data of 8728 HF patients with a first recorded LVEF <40% and a later (≥1 month) recorded LVEF ≥40% and guideline-recommended RAASi or beta-blocker (BB) treatment who were included in the Swedish HF registry between June 11, 2000, and December 31, 2023, were collected. At the time of the first recording (i.e., LVEF <40%), 8350 participants (95.7%) were receiving RAASi/ARNI treatment, 8189 (93.8%) were taking BBs, and 4055 (46.5%) were on MRAs. Treatment withdrawal was defined as a patient reported to be “on treatment” by the treating physician at the first registration (reduced LVEF) but not at the second registration (improved LVEF). Median follow-up duration was 12 months (25th–75th percentiles: 11.4–12).
Outcomes
The primary endpoint was a composite outcome of time to CV death or first HF hospitalization. Secondary endpoints were the individual components of the primary endpoint.
Main results
Rates and predictors of GDMT withdrawal
- At the time of the improved LVEF registration (i.e., ≥40%), RAASis/ARNIs were withdrawn in 366 patients (4.4%), BBs in 270 (3.3%), and MRAs in 696 (17.2%).
- Patient characteristics that were independently associated with a higher likelihood of withdrawal of RAASi/ARNI, BB, or MRA were nonuse of other GDMTs for HFrEF, higher LVEF (≥50% vs. 40%–49%) at the time of the improved LVEF recording, and a longer time between the 2 LVEF recordings (all P<0.05).
Relationship between withdrawal and adverse events
- In Cox regression analysis with overlap weighting, the incidence rate of the primary endpoint of CV death or first HF hospitalization at 1 year was increased in patients in whom RAASi/ARNI was withdrawn compared with those who continued this treatment (HR: 1.38; 95%CI: 1.08–1.77).
- For RAASi/ARNI withdrawal versus continuation, the 1-year absolute risk difference was 6.0%, the number needed to harm (NNH) was 17, and the difference in restricted mean survival time was –17.6 days (95%CI: –31.4 to –3.7).
- The risk of the primary endpoint was also increased for MRA withdrawal compared with continuation (HR: 1.36; 95%CI: 1.07–1.73). The 1-year absolute risk difference was 3.9%, the NNH was 25, and the difference in restricted mean survival time was –11.2 days (–19.1 to –3.4).
- There was no significant association of BB withdrawal and the primary endpoint (HR: 1.00; 95%CI: 0.70–1.42).
- Subgroup analysis indicated BB withdrawal was associated with a higher risk of the primary endpoint in patients in whom the LVEF improved to 40%–49% (HR: 1.31; 95%CI: 0.89–1.95) than those with LVEF improvement to ≥50% (HR: 0.51; 95%CI: 0.23–1.10; P for interaction=0.03).
Conclusion
In this retrospective observational study based on Swedish HF registry data among HFrEF patients with improved LVEF, rates of GDMT withdrawal were low (4% for RAASi/ARNI, 3% for BB, and 17% for MRA). Withdrawal of RAASi/ARNI treatment or MRAs was associated with a higher risk of CV death or HF hospitalization at 1 year. BB withdrawal was not independently associated with adverse events, although the risk seemed to be increased in patients with less LVEF improvement (40%–49% vs. ≥50%). According to the authors, this suggested “better outcomes with continuing BB only until EF improves up to 50%.”
References
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