Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial
Key result
Rapid up-titration of GDMT cuts 180-day HF readmission or death ~34% vs usual care.
- RR 0.66
- 95% CI 0.50-0.86
- P=0.0021
- n=1,078
Why the study?
There was a paucity of evidence regarding the optimal dose and pace of up-titration of guideline-directed medical therapies after hospital admission for acute heart failure.
Does high-intensity up-titration of guideline-directed medical therapies reduce 180-day heart failure readmission or all-cause death in patients admitted with acute heart failure?
Population
1078 patients aged 18-85 years hospitalized for acute heart failure not on full-dose guideline-directed treatment
Comparison
High-intensity care vs usual care
Design
Multinational, open-label, parallel-group randomised controlled trial
Follow-up
180 days
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.
“Patients will love these results because for the first time we're going to tell them, 'If you take full-dose medications, you will have an immediate positive effect.' And for clinicians, who may be concerned about potential adverse effects associated with ramping up doses of multiple medications all at once, we are telling them it's safe.”
GCGregg C. FonarowDirector, Ahmanson-UCLA Cardiomyopathy Center, UCLA
“Despite the availability of multiple medications proven to substantially extend survival and improve symptoms, most patients with HF will have their disease progress and many will ultimately die without ever receiving all of these therapies, despite being eligible.”
AVAmanda VestCardiologist, Tufts Medical Center
“The trial offers additional encouragement and further motivates us to find systems of care that optimize medical therapy in this vulnerable period after a hospitalization.”
Implication
Rapid up-titration of guideline-directed medical therapy with close follow-up after acute heart failure admission significantly reduces the risk of 180-day all-cause death or heart failure readmission.
Key Points
- This research aims to evaluate the safety, tolerability, and efficacy of high-intensity care through rapid up-titration of medications in acute heart failure.
- Multinational, open-label, randomized, parallel-group design with 1078 participants.
- Patients assigned to high-intensity care received full doses of medications and close follow-up compared to usual care.
- Primary endpoint assessed was 180-day readmission due to heart failure or all-cause death.
- Heart failure readmission or all-cause death rate was 15.2% in high-intensity care vs 23.3% in usual care (adjusted risk difference 8.1%, p=0.0021).
- Higher percentage of full medication dosages achieved in the high-intensity care group for key medications.
- More total adverse events reported in high-intensity care (41%) compared to usual care (29%), but serious adverse events were similar.
Study Design
Type
RCT (n=1,078)
Blinding
Open-label
Randomization
1:1, stratified by left ventricular ejection fraction (≤40% vs >40%) and country
Multicenter
Yes
Structured PICO
Does high-intensity up-titration of guideline-directed medical therapies reduce 180-day heart failure readmission or all-cause death in patients admitted with acute heart failure?
P
Population
1,078 patients aged 18-85 years admitted with acute heart failure and not on full doses of guideline-directed medical therapy, followed for 180 days.
I
Intervention
High-intensity care involving up-titration of guideline-directed medical therapies to 100% of recommended doses within 2 weeks of discharge, plus 4 scheduled outpatient visits over 2 months after discharge monitoring clinical status, laboratory values, and NT-proBNP concentrations.
C
Comparator
Usual care (followed usual local practice).
O
Outcome
180-day readmission to hospital due to heart failure or all-cause death.composite
Main Result
Relative Risk: 0.66 (95% CI 0.5–0.86)
Absolute Event Rate: 15.2% vs 23.3%
Absolute Risk Reduction: 8.1%
p-value: p=0.0021
Rapid up-titration of guideline-directed medical therapy with close follow-up after acute heart failure admission significantly reduces the risk of 180-day all-cause death or heart failure readmission.
Limitations
- Study was stopped early per the data and safety monitoring board's recommendation
- Protocol amendment to the primary endpoint required down-weighting of results for patients enrolled on or before the amendment
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Mebazaa et al. (2022) conducted an RCT in Acute heart failure (n=1,078). High-intensity care (rapid up-titration of guideline-directed medical therapies) vs. Usual care was evaluated on 180-day readmission to hospital due to heart failure or all-cause death (RR 0.66, 95% CI 0.50-0.86, p=0.0021). Rapid up-titration of guideline-directed medical therapies reduced 180-day heart failure readmission or all-cause death compared with usual care (15.2% vs 23.3%; RR 0.66; 95% CI 0.50-0.86; p=0.0021).