Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction
Key result
Under 1% of eligible HFrEF patients achieve target triple-therapy doses over 12 months.
- n=2,588
Why the study?
Guidelines recommend titration of medical therapy for HFrEF to target doses, but the degree to which titration occurs in contemporary US practice is unknown.
Population
2,588 US outpatients with chronic HFrEF in the CHAMP-HF registry without contraindications
Comparison
Longitudinal use and dosing changes of ACEI/ARB, ARNI, beta-blocker, and MRA
Design
Registry-based longitudinal observational study
Follow-up
12-month
Authors
Discussion
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Member takes
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
TATariq AhmadCardiologist, Yale School of Medicine
“This is the reality we live with in heart failure, without any meaningful outrage or accountability. Medical therapies that scaled a burden-of-proof barrier unprecedented in most disease states have invariably fallen flat in the implementation phase.”
“In the CHAMP-HF registry conducted in the United States, which included 2,588 patients with HFrEF who completed follow-up to 12 months, only 1.5% of patients were taking the stable target dose for 12 months.”
Implication
Target-dose GDMT remains rare in HFrEF outpatients; leaves open effective strategies to close the implementation gap.
Key Points
- To characterize longitudinal titration of guideline-directed medical therapy in outpatients with chronic heart failure with reduced ejection fraction and identify factors associated with medication changes.
- Analyzed 2,588 US outpatients with chronic HFrEF enrolled in the CHAMP-HF registry between December 2015 and July 2017 with complete medication data and no therapy contraindications.
- Evaluated use and dosing of ACEI/ARB, ARNI, beta-blocker, and MRA at baseline and 12-month follow-up to track dosing stability, dose increases, and dose discontinuations.
- At baseline, target doses were received by 25% (n=658) of patients for MRA, 20% (n=525) for beta-blocker, 11% (n=287) for ACEI/ARB, and 2% (n=45) for ARNI.
- At 12 months, rates of initiation or dose increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding rates of discontinuation or dose decrease were 4%, 7%, 11%, and 3%.
- Over 12 months, <1% of patients (0.7%, n=17) were simultaneously treated with target doses of ACEI/ARB/ARNI, beta-blocker, and MRA, with medical reasons accounting for 54% to 56% of discontinuations across classes.
Study Design
Type
Observational (n=2,588)
Multicenter
Yes
Structured PICO
P
Population
2,588 adult outpatients in the US with chronic heart failure with reduced ejection fraction (LVEF ≤40%) followed for 12 months to assess longitudinal titration of medical therapy.
E
Exposure
Guideline-directed medical therapy (ACEI/ARB, ARNI, beta-blocker, MRA) titration in routine clinical practice
O
Outcome
Use and dose of ACEI/ARB, ARNI, beta-blocker, and MRA at baseline and 12-month follow-up, and factors associated with medication changes
In contemporary US practice, the vast majority of eligible HFrEF patients do not achieve target doses of guideline-directed medical therapy over 12 months of follow-up, highlighting significant gaps in care optimization.
Limitations
- Observational data cannot definitively determine cause-effect relationships
- Excluded patients with interval death or lost-to-follow-up
- Data derived from medical records may have incomplete documentation (e.g., undocumented contraindications)
- Participating sites may not be generalizable to all outpatient facilities
- Registry permitted multiple reasons for medication changes without discerning the primary reason
- Observational data cannot definitively determine cause-effect relationships.
- Excludes patients with interval death or lost-to-follow-up.
- Relies on medical record documentation, which may miss undocumented contraindications or prior intolerance.
- Participating sites may not be generalizable to all outpatient facilities and HFrEF patients.
- Cannot discern the primary reason for medication changes when multiple reasons were selected.
Cite This Study
Greene et al. (2019) conducted an observational in Heart failure with reduced ejection fraction (HFrEF) (n=2,588). Guideline-directed medical therapy (ACEI/ARB, ARNI, beta-blocker, MRA) was evaluated on Longitudinal titration of HFrEF medical therapy (initiation/dosing increase or discontinuation/dosing decrease) at 12 months. Over 12 months of follow-up, less than 1% of eligible HFrEF patients were simultaneously treated with target doses of ACEI/ARB/ARNI, beta-blocker, and MRA, with few patients having doses increased over time.