1) The STRONG-HF trial compared a high-intensity follow-up approach focused on rapid up-titration of guideline-directed medical therapies (GDMT) for heart failure to target doses within 90 days of hospital discharge to standard post-discharge care. 2) The high-intensity approach resulted in significantly higher rates of patients reaching target doses of renin-angiotensin-aldosterone inhibitors, beta-blockers, and mineralocorticoid receptor antagonists by 90 days compared to standard care. 3) At 180 days, the high-intensity approach reduced the combined outcome of all-cause death or heart failure readmission compared to standard care and improved quality of life, with no

1. Dr. Chhabi Satpathy
Professor and Head
Department of Cardiology
MKCG Medical College
Berhampur
Odisha
STRONG - HF TRIAL
Safety, tolerability and efficacy of up-titration of guideline-directed medical
therapies for acute heart failure : a multinational, open label, randomised, trial

2. INTRODUCTION
• The “Vulnerable period”
• No close follow-up
• Rarely reach full dose GDMT
• Paucity of evidence and mixed results

4. • The ESC 2022 guidelines
- Level of evidence is C
Eur J Heart Fail 2022; 24: 4-131

5. 2022 AHA/ACC/HFSA Joint Committee Guidelines: “In patients being discharged after hospitalization for worsening HF,
an early follow-up, generally within 7 days of hospital discharge, is reasonable to optimize care and reduce
rehospitalization” (Class 2a, LOE B-NR)
“Multidisciplinary systems of care that promote improved communication between health care professionals, systematic
use and monitoring of GDMT, medication reconciliation, and consistent documentation are examples of patient safety
standards that should be ensured for all patients with HF transitioning out of the hospital.”
Circulation. 2022; 145(18):e895-e1032

6. OBJECTIVE
To compare high-intensity early follow-up from AHF hospitalization with rapid up-titration
of GDMT to target doses within 2-3 weeks of discharge to standard post-discharge usual
care.

7. STUDY DESIGN
Multinational: 14 countries and 87 hospitals
Open-label trial
1:1 parallel-group randomization

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9. Usual care: Discharge and follow-up according to local practice for 90 days
High-intensity care: algorithm-based treatment:
Optimization of oral heart failure therapies
i. First dose adjustment immediately after randomization (within 2 days before anticipated hospital discharge)
- prescribed at least half of optimal dose of BB, ACE/ARB/ARNi, and MRA
ii. Two weeks after randomization, uptitration to full target dose of BB, ACE/ARB/ARNi, and MRA, as tolerated

10. iii. Frequent visits with circulating NT-proBNP measured
- Assessed by the study team at 1, 2, 3, and 6 weeks after randomization for safety and tolerability by
doing full physical examination and lab assessment of NT-proBNP, electrolytes, kidney function, and Hb%
- Diuretics increased based on congestion on physical exam and NT-proBNP

11. OUTCOMES
1. Primary Outcome
- 180-day heart failure readmission or all-cause death
2. Secondary Outcomes
- Change in quality of life from baseline to day 90 (EQ-5D visual analog scale)
- Change in 180-day all-cause death
- Change in 90-day heart failure readmission or all-cause mortality

12. STATISTICAL ANALYSIS
1. Intention-to-treat protocol
2. Countries combined into regions for analysis, given the sparseness of events in some countries
3. Protocol amended to increase sample size and change primary endpoint from 90-day to 180-day mid-way
given lower than expected event rate
4. The trial terminated when approximately 1000 patients had 90-day follow-up data given larger than expected
risk reduction of the primary endpoint in the high-intensity care group

13. RESULTS
1. N = 1085 (542 to high intensity, 536 to usual care)
2. Average age: 63.0 ±13.6 yrs
3. Male: 662 (61%) , Female 423 (39%)
4. Race/Ethnicity: 77% white, 21% Black, ≤1% all other
5. Average LVEF: 36.3% (±12.52%)
6. LVEF ≤40%: 68%
7. LVEF >50%: 15% Ischemic cardiomyopathy: 48% Ischemic cardiomyopathy: 48%

14. Rates of up-titration of meds :
Percentage of patients on target dose of medication by day 90 were :
1. Renin angiotensin aldosterone inhibition:
High-intensity group: 55% v/s Usual care group: 2%
2. Beta-blockers:
High-intensity group: 49% v/s Usual care group: 4%
3. Mineralocorticoid receptor antagonist:
High-intensity group: 84% v/s Usual care group: 46%

15. Oral guideline-directed medical
therapies for heart failure prescribed, in
high-intensity care and usual care
groups by visit
Lancet. 2022 Dec 3;400(10367):1938-1952

16. 1. Average visits in 90 days: 4.8 in high intensity group vs 1.0 in usual care group
2. Adjustment treatment effect in vitals and labs:
i. Systolic blood pressure (mmHg): -5.4 (-7.2 to –3.5), p < 0.0001
ii. Diastolic blood pressure (mmHg): -2.3 (-3.5 to –1.1), p = 0.0001
iii. Pulse (bpm): -5.8 (-7.3 to –4.3), p < 0.0001
iv. NYHA class: 1.36 (1.22 to 1.53), P < 0.0001
v. Bodyweight (kg): -1.36 (-1.91 to –0.80), p < 0.0001
vi. Potassium (mmol/L): 0.15 (0.09 to 0.21), p < 0.0001

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18. Adjusted Kaplan-Meier
estimates of cumulative
event-free survival with
down-weighting of cohort
1 for all-cause death or
heart failure readmission
(A), all-cause death or
heart failure excluding
deaths due to COVID-19
(B), all-cause mortality (C),
and all-cause mortality
excluding deaths due to
COVID-19 (D), from
randomisation up to day
180
Lancet. 2022 Dec
3;400(10367):1938-1952

19. Prespecified and post-hoc subgroup analysis
of primary endpoint (difference in 180-day
risk of all-cause death or heart failure
readmission)
Lancet. 2022 Dec 3;400(10367):1938-1952

20. Adverse Events
223/542 patients in the high-intensity group (41%) vs. 158/536 in the usual care group (29%)
Most commonly observed adverse events: cardiac failure, hypotension, hyperkalemia, renal
impairment, with non-significant differences in occurrences between groups
1. Hypotension 5% vs. <1%
2. Hyperkalemia 3% vs. 0
3. Renal impairment 3% vs. <1%
4. Bradycardia 0.7% vs. 0.4%

21. CONCLUSION
In this multinational, randomized, open-label trial involving patients discharged following acute heart failure
admission, rapid up-titration of GDMT with scheduled follow-up to achieve specific target doses in the first 90
days was associated with a reduction in 180-day all-cause death or heart failure readmission, improved quality
of life, and reduced symptom burden.
There was no significant difference in serious adverse outcomes.

22. LIMITATIONS
1. Study amended to change primary endpoint from 90 day to 180 day death or HF readmission due to low
event rate
2. Study was stopped early due to very high significant difference between the groups
3. Study was unblinded which may have affected the perception of study team
4. Cause of readmissions were not adjudicated and were based on investigator’s determination
5. SGLT2i were implemented late in the study as it was not approved at the time of beginning of study