STRONG-HF Trial: Rapid Optimization of Heart Failure Therapy
Core Strategy of STRONG-HF
The STRONG-HF trial demonstrated that rapid, aggressive uptitration of guideline-directed medical therapy (GDMT) to 100% optimal doses within 2 weeks after acute heart failure discharge significantly reduces heart failure readmissions and mortality. 1
The trial employed a high-intensity care approach with forced-titration protocols, challenging the traditional slow, sequential medication optimization that has contributed to persistent underutilization of GDMT in clinical practice. 1
Key Findings and Outcomes
Dose Achievement and Clinical Benefits
Achieving higher GDMT doses at 2 weeks post-discharge was associated with substantial outcome improvements: for every 10% increase in average percentage of optimal dose, there was an 11% reduction in 180-day heart failure readmission or death (adjusted HR 0.89,95% CI 0.81-0.98) and a 16% reduction in all-cause mortality (adjusted HR 0.84,95% CI 0.73-0.95). 1
At 2 weeks, 43.1% of patients achieved high doses (≥90% of optimal), 49.3% achieved medium doses (50-90%), and only 7.6% remained at low doses (<50%). 1
Quality of life improved more in patients treated with higher GDMT doses, with the high-dose group showing greater improvement on the EQ-5D visual analog scale compared to the low-dose group. 1
Safety Profile
Adverse events occurred LESS frequently in patients prescribed higher GDMT doses at week 2, contradicting common clinical concerns about aggressive uptitration. 1
The rapid uptitration strategy proved both feasible and safe in most patients, even those recently hospitalized for acute decompensation. 1
Implementation Protocol
Medication Classes Targeted
The STRONG-HF protocol focused on three core medication classes for rapid optimization: 1
- Renin-angiotensin system inhibitors (ACE inhibitors, ARBs, or preferably ARNI)
- Beta-blockers (carvedilol, metoprolol succinate, or bisoprolol)
- Mineralocorticoid receptor antagonists (spironolactone or eplerenone)
Uptitration Timeline
All medications were started at low doses and aggressively uptitrated with the goal of reaching 100% optimal doses within 2 weeks after hospital discharge. 1
Close monitoring with N-terminal pro-brain natriuretic peptide (NT-proBNP) testing guided therapy adjustments, distinguishing this approach from traditional care. 1
Clinical Barriers Identified
Patient Characteristics Associated with Lower Dose Achievement
Patients with lower blood pressure at baseline were less likely to be uptitrated to optimal GDMT doses at week 2. 1
Patients with more persistent congestion faced greater challenges in achieving target doses. 1
However, these barriers were not absolute contraindications—the trial demonstrated that even in these challenging subgroups, aggressive uptitration remained beneficial and safe. 1
Integration with Current Guidelines
Alignment with Contemporary Recommendations
The STRONG-HF approach supports the 2022 ACC/AHA/HFSA guideline recommendation to initiate all four foundational GDMT medication classes simultaneously at low doses, rather than sequential initiation. 2, 3
The trial validates the forced-titration strategy now endorsed by major guidelines, where medications are started together and uptitrated at specific intervals (typically every 1-2 weeks) until target doses are achieved. 4
Current guidelines recommend monitoring blood pressure, renal function, and electrolytes at 1-2 weeks after each dose increment, consistent with the STRONG-HF monitoring protocol. 3, 5
Practical Application
When to Apply STRONG-HF Principles
In-hospital initiation of GDMT substantially improves post-discharge medication use compared to deferring initiation to the outpatient setting, making the hospitalization an ideal opportunity to begin aggressive optimization. 4
Continue GDMT in hospitalized patients except when hemodynamically unstable or contraindicated, as temporary discontinuation often leads to failure to reinitiate. 3, 4
Overcoming Clinical Inertia
Asymptomatic or mildly symptomatic low blood pressure should not be a reason for GDMT reduction or cessation—patients with adequate perfusion can tolerate systolic BP 80-100 mmHg. 2
Modest increases in creatinine (up to 30% above baseline) are acceptable and should not prompt discontinuation of therapy, as these changes typically stabilize with continued treatment. 4
Temporary symptoms of fatigue and weakness with dose increases usually resolve within days and should not trigger premature dose reduction. 4
Critical Distinction from Standard Care
The STRONG-HF trial's most important contribution is demonstrating that rapid, aggressive uptitration is not only safe but superior to gradual optimization. 1 This challenges decades of conservative practice patterns where clinicians slowly titrate medications over months, often never reaching target doses. The trial showed that 43% of patients can achieve ≥90% of optimal doses within just 2 weeks when using a systematic, intensive approach. 1