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GDMT Intensity at Hospital Discharge and Associated Clinical Outcomes in Heart Failure: A Systematic Review and

Sergio Alejandro Gómez-Ochoa1,2, Lyda Z Rojas3, Carlos A Corona-Arias4

  • 1Heart Failure and Heart Transplant Clinic, Fundación Cardiovascular de Colombia, Floridablanca 681004, Colombia.

Journal of Clinical Medicine
|July 15, 2026
PubMed

Insights

Guideline-directed medical therapy (GDMT) intensity at hospital discharge is linked to better heart failure (HF) outcomes. Higher GDMT intensity, especially quadruple therapy, shows a significant association with reduced mortality and HF hospitalizations.

Area of Science:

  • Cardiology
  • Pharmacology
  • Clinical Research

Background:

  • Contemporary heart failure (HF) guidelines advocate for early initiation of four foundational drug classes in heart failure with reduced ejection fraction (HFrEF).
  • Real-world prescription rates of guideline-directed medical therapy (GDMT) at hospital discharge are suboptimal.
  • Limited comparative data exists on the impact of GDMT intensity at discharge on clinical outcomes.

Purpose of the Study:

  • To explore the association between GDMT intensity prescribed at or before hospital discharge and clinical outcomes in HFrEF patients.
  • To analyze real-world prescription patterns of GDMT in the SGLT2i era.
  • To compare the effectiveness of different GDMT regimen intensities.

Main Methods:

  • A systematic search of MEDLINE and EMBASE databases was conducted.
  • A frequentist random-effects network meta-analysis was performed, grouping regimens into four intensity nodes (single/none, double, triple, quadruple).
  • The primary outcome was the composite of all-cause mortality (ACM) and HF hospitalization (HFH), with secondary outcomes including HFH, ACM, and cardiovascular mortality. Confidence in estimates was rated using CINeMA.

Main Results:

  • Twenty-seven studies involving 73,174 patients were included; quadruple therapy was prescribed in only 34% of SGLT2i-era cohorts.
  • Higher GDMT intensity was associated with progressively lower event rates for the primary composite endpoint: double therapy (HR 0.76), triple therapy (HR 0.72), and quadruple therapy (HR 0.52).
  • A consistent ordinal gradient was observed across outcomes, with quadruple therapy showing the best numerical ranking where estimable. Associations are not causal due to observational data.

Conclusions:

  • Discharge GDMT intensity represents a significant opportunity to improve outcomes for patients with HF.
  • Current prescription rates for intensive GDMT regimens remain low.
  • Adequately powered randomized trials are necessary to establish the definitive incremental benefit of intensive GDMT and bridge the evidence-practice gap.

Keywords:
SGLT2 inhibitorsguideline-directed medical therapyheart failurehospital dischargemortalitynetwork meta-analysis

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