When to Start All Four Pillars of Heart Failure Management
All four pillars of heart failure management should be initiated simultaneously at low doses as soon as a patient is diagnosed with heart failure with reduced ejection fraction (HFrEF), followed by gradual uptitration. 1, 2
The Four Pillars of HFrEF Management
The four pillars of guideline-directed medical therapy (GDMT) for HFrEF include:
- SGLT2 inhibitors (empagliflozin or dapagliflozin) 3
- Beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) 4
- Mineralocorticoid receptor antagonists (MRAs) (spironolactone or eplerenone) 4
- Renin-angiotensin system inhibitors (ARNI preferred, or ACEi/ARB if ARNI not feasible) 3
Implementation Strategy
Initial Approach
- Start all four medication classes simultaneously at low doses with gradual titration, beginning with SGLT2 inhibitors and MRAs due to their minimal effect on blood pressure 1, 2
- Evaluate blood pressure, heart rate, volume status, and renal function before initiation 2
- Adjust diuretics according to volume status to avoid overdiuresis which can lead to hypotension 2
Recommended Sequence Based on Blood Pressure
For patients with adequate blood pressure:
For patients with low blood pressure (SBP <100 mmHg):
Titration and Monitoring
- Medications should be started at low doses and titrated gradually every 2-4 weeks as tolerated 1
- Monitor renal function, electrolytes, blood pressure, and heart rate regularly, especially when using ACEi/ARB/ARNi and MRAs 1
- During active titration, regularly check serum electrolytes, urea nitrogen, and creatinine 1
Special Considerations
During Hospitalization
- In patients with HFrEF requiring hospitalization, GDMT should be initiated during hospitalization after clinical stability is achieved 4
- Preexisting GDMT should be continued and optimized during hospitalization, unless contraindicated 4
- Even in patients experiencing mild decrease of renal function or asymptomatic reduction of blood pressure during hospitalization, diuresis and other GDMT should not routinely be discontinued 4
Common Pitfalls to Avoid
- Avoid the traditional step-by-step approach that delays benefits of comprehensive therapy 2
- Don't be overly cautious with dosing - even lower-than-target doses provide significant benefits 2
- Excessive diuresis can lead to hypotension and impair tolerance of other HF medications 2
Evidence Supporting Early Quadruple Therapy
- Recent research demonstrates that early and simultaneous initiation of all four pillars is associated with reduced risk of heart failure hospitalization during the vulnerable phase after discharge, compared to a conventional stepwise approach 5
- A prospective study showed that patients who achieved quadruple therapy within 4 weeks had better outcomes than those who did not, with a reduced risk of the combined outcome of all-cause hospitalization or death 6
- Early initiation of quadruple therapy is clinically feasible and safe when implemented in selected patients 6
Benefits of Early Comprehensive Therapy
- Simultaneous initiation of all four pillars provides more rapid improvement in outcomes than sequential addition 5
- Even in hospitalized patients, continuation or initiation of GDMT is associated with lower risk of post-discharge death and readmission 4
- Approximately 46% of patients could receive all four foundational drugs at discharge, potentially providing prognostic advantages 7
By implementing all four pillars of heart failure management simultaneously at diagnosis and titrating gradually, clinicians can optimize outcomes for patients with HFrEF.