GDMT for Heart Failure

Heart Failure 4 sources · Updated Jul 16, 2026

This review helps pharmacists integrate the four-pillar heart failure regimen, new finerenone evidence across ejection fractions, and cardiorenal comanagement into concrete discharge and monitoring actions.

Bottom Line

Full four-pillar guideline-directed medical therapy remains the foundation for heart failure with reduced ejection fraction, and finerenone now extends disease-modifying options into the mildly reduced and preserved ejection fraction range, but the persistent gap is implementation in the highest-risk patients rather than a lack of proven therapies.

0.84

rate ratio, total primary events

Class I

SGLT2i recommendation in HFrEF

41.6%

in-hospital SGLT2i initiation, HFrEF

11.4%

SGLT2i uptake, prior HF hospitalization

State of Play

Heart failure management has consolidated around a four-pillar guideline-directed medical therapy (GDMT) regimen for reduced ejection fraction and an expanding role for sodium-glucose co-transporter-2 inhibitors (SGLT2i) across the full ejection fraction spectrum. The pharmacologic toolkit is now robust, but uptake data show the bottleneck has shifted from evidence to implementation, especially in previously hospitalized patients.

What Changed

The 2022 AHA/ACC/HFSA guideline elevated SGLT2i to Class I in heart failure with reduced ejection fraction (HFrEF) and gave them a role in mildly reduced and preserved ejection fraction, while making sacubitril/valsartan first-line. FINEARTS-HF then provided the first prospective randomized evidence that finerenone reduces worsening heart failure events in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), and a KDIGO consensus reframed how eGFR changes should be interpreted during GDMT titration.

How It Fits the Guidelines

The 2022 AHA/ACC/HFSA guideline gives steroidal mineralocorticoid receptor antagonists (MRAs) only a weak Class 2b recommendation in HFpEF, reflecting the neutral TOPCAT result, so FINEARTS-HF fills a gap the current guideline does not yet address for the nonsteroidal agent finerenone. The KDIGO consensus aligns with the AHA/ACC/HFSA and European Society of Cardiology (ESC) frameworks but adds nuance by folding chronic kidney disease into heart failure staging and reconciling the differing eGFR initiation thresholds across agents.

Evidence at a Glance

Source	Key finding	Grade / Verdict
2022 AHA/ACC/HFSA Heart Failure Guideline: Major Revisions to GDMT and Phenotypes Guideline · Circulation guideline backbone Establishes the four-pillar GDMT framework and elevates SGLT2i to Class I, anchoring the entire topic.	Class I recommendation for SGLT2 inhibitors in HFrEF	Grade: Moderate Practice-changing
Finerenone Cuts Heart Failure Events in HFmrEF and HFpEF Study · N Engl J Med new pillar evidence FINEARTS-HF provides the first prospective randomized evidence that finerenone reduces worsening heart failure events in HFmrEF/HFpEF.	Total primary events rate ratio 0.84, 95% CI 0.74-0.95	Grade: High Practice-changing
KDIGO Consensus Reframes Kidney-Heart Failure Comanagement Priorities Study · Kidney international cardiorenal comanagement framing KDIGO consensus reframes eGFR interpretation and hyperkalemia management to keep patients on disease-modifying therapy.	Continue GDMT through stable eGFR decline of 10%-30% after initiation	Grade: Low Confirmatory
SGLT2 Inhibitor Uptake Rises but Misses Highest-Risk HFrEF Patients Study · BMC cardiovascular disorders real-world uptake gap Documents strong overall post-guideline SGLT2i uptake but a paradoxical prescribing gap in the highest-risk HFrEF patients.	SGLT2i initiation only 11.4% in patients hospitalized in prior 12 months	Grade: Low Hypothesis-generating

Practice Considerations

Confirm all four GDMT pillars—evidence-based beta-blocker, angiotensin receptor-neprilysin inhibitor (ARNi) or angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB), MRA, and SGLT2i—are addressed for eligible HFrEF patients regardless of diabetes status, treating SGLT2i as part of a bundle rather than an isolated add-on.
Consider finerenone as a disease-modifying option in HFmrEF/HFpEF (LVEF 40% or greater) with elevated natriuretic peptides, understanding it reduces worsening heart failure events and modestly improves symptoms but has not demonstrated a mortality benefit.
Layer finerenone with an SGLT2i rather than choosing between them, since FINEARTS-HF preserved benefit regardless of baseline SGLT2i use, while instituting baseline and serial potassium and creatinine monitoring given the roughly doubled rate of potassium above 5.5 mmol/L.
Do not reflexively discontinue GDMT for a stable eGFR decline of up to 30% after initiation; per the KDIGO consensus, contextualize this as an expected hemodynamic dip and manage hyperkalemia proactively instead of dropping disease-modifying agents.
At discharge reconciliation, flag the highest-risk gap group—patients with a heart failure hospitalization in the prior 12 months, who received SGLT2i at only 11.4%—for inpatient GDMT initiation.
Reconcile the differing eGFR initiation thresholds across agents (SGLT2i down to eGFR >20, ARNi requires eGFR >30, finerenone at eGFR >25 with type 2 diabetes and albuminuria) when building a regimen in patients with concurrent chronic kidney disease.

Open Questions

Will heart failure guidelines formally incorporate nonsteroidal MRAs such as finerenone for HFmrEF/HFpEF, and how will they position it relative to steroidal MRAs?
Does adding finerenone to an SGLT2i produce incremental hard-outcome benefit, given that only 13.6% of FINEARTS-HF patients were on an SGLT2i at baseline?
Is there an independent SGLT2i effect on readmission separate from co-prescribed GDMT, which the observational uptake data could not isolate?
What are the optimal dosing and monitoring standards for these agents in advanced chronic kidney disease, where randomized data are largely absent?

finerenone SGLT2 inhibitors dapagliflozin empagliflozin sacubitril/valsartan ARNi beta-blockers mineralocorticoid receptor antagonists spironolactone HFrEF HFmrEF HFpEF

🎓

Synthesized and reviewed by a licensed pharmacist

Each topic review is built from our published deep analyses and checked for clinical accuracy before it goes live.

Not medical advice. PharmD Signal provides educational synthesis of published pharmacy and medical literature for practicing pharmacists. It is not a treatment recommendation for any individual patient; clinical decisions remain the responsibility of the treating clinician exercising independent professional judgment.

← Back to Hot Topics