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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
Summary
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.
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