When to onboard GDMT (Guideline-Directed Medical Therapy)?

When to Onboard GDMT for Heart Failure

Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) should be initiated during hospitalization before discharge for all eligible patients, as this approach significantly reduces mortality and readmissions compared to delaying therapy to the outpatient setting. 1

Timing of GDMT Initiation

In-Hospital Initiation

• The ACC/AHA guidelines provide a Class I recommendation for in-hospital or before hospital discharge initiation of GDMT if not previously established and not contraindicated 1
• Hospitalization for heart failure represents a critical opportunity to improve GDMT utilization, as failure to discharge eligible patients on GDMT significantly increases the chance therapies will never be started or will be delayed by months to years 1
• Studies show that deferring initiation of therapies like ARNI or MRA to the outpatient setting carries a >75% chance that therapy will not be initiated within the next year 1

Benefits of Early Initiation

• SGLT2 inhibitors demonstrate early clinical benefits within days to weeks of initiation, with empagliflozin showing a 58% relative reduction in mortality, HF hospitalization, or urgent HF visits at just 12 days after initiation 1
• The SOLOIST-WHF trial confirmed efficacy and safety of SGLT2 inhibitors when initiated either pre-discharge or early post-discharge 1
• Not prescribing GDMT at discharge exposes patients to statistically and clinically significant excess risk for death and readmission in the first days to weeks post-discharge 1

Implementation Strategy

Sequential Medication Introduction

1. Beta-blockers should be started first in the quadruple therapy regimen 2
2. RAS inhibitors (ACEi/ARB or ARNI) should be added next 2
3. MRAs (spironolactone or eplerenone) should be added after ARNI 2
4. SGLT2 inhibitors (dapagliflozin or empagliflozin) should be added as the fourth component 2

Patient Selection Considerations

• Location of care (inpatient vs. outpatient) should not factor into decisions to withhold chronic HFrEF therapies 1
• Focus on objective measures like vital signs and laboratory values rather than hospitalization status when deciding on GDMT initiation 1
• SGLT2 inhibitors can improve tolerance of other heart failure therapies by decreasing risk of hyperkalemia and slowing progression of kidney dysfunction 1

Post-Discharge Follow-up

• Schedule an early follow-up visit within 7 to 14 days and telephone follow-up within 3 days of hospital discharge 1
• At the first post-discharge visit, address:
  • Titration and optimization of chronic oral HF therapy
  • Assessment of volume status and blood pressure
  • Renal function and electrolytes
  • Reinforcement of HF education and medication adherence 1

Addressing Common Barriers to GDMT Implementation

Patient Education

• The EPIC-HF trial demonstrated that patient activation tools (3-minute video + 1-page checklist) sent before clinic visits increased GDMT intensification from 29.7% to 49.0% within 30 days 1
• Less than 25% of patients with HF in the US are familiar with ARNI and MRA therapies, and 25-45% have concerns about medication safety or effectiveness 1
• Patient education is modifiable and direct-to-patient approaches can improve quality of care 1

Medication Tolerability

• In clinical trials, adverse events (AEs) are reported in 75-85% of participants across all GDMT classes, but there is generally no significant difference in AE frequency between intervention and placebo arms 1
• Many adverse events attributed to GDMT may actually be manifestations of heart failure itself rather than medication side effects 1, 2
• Even if all four drug classes cannot be introduced, a regimen with a simple GDMT score ≥5 (based on medication combinations and dosages) may lead to improved prognosis 2, 3

Pitfalls to Avoid

• Delaying initiation: Waiting until outpatient follow-up significantly reduces the likelihood of patients ever receiving GDMT 1
• Inappropriate discontinuation: Many symptoms attributed to GDMT may actually be manifestations of HF itself 1, 2
• Inadequate dose titration: Target doses should be achieved whenever possible, as even suboptimal doses provide benefit compared to no therapy 2
• Waiting for clinical deterioration: GDMT should be initiated proactively rather than reactively 2

By implementing GDMT during hospitalization and ensuring proper follow-up, clinicians can significantly improve outcomes for patients with heart failure, reducing mortality and preventing readmissions.