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Rapid Uptitration of GDMT and HF Outcomes
Quick Takes
- In a post hoc analysis of a randomized controlled trial of hospitalized HF patients, intensive outpatient guideline-directed medical therapy (GDMT) titration correlated with sustained decongestion at day 90 compared to usual care, irrespective of prerandomization congestion status.
- All-cause mortality and first HF rehospitalization at 180 days were lower in the intensive GDMT arm compared with usual care, irrespective of prerandomization congestion status.
Study Questions:
What is the relationship between intensive uptitration of guideline-directed medical therapy (GDMT) for heart failure (HF) during the early post-discharge period, and what are the outcomes?
Methods:
This is a post hoc analysis of STRONG-HF (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro–Brain Natriuretic Peptide [NT-proBNP] Testing of Heart Failure Therapies), a multicenter trial enrolling 1,078 adults hospitalized with HF. Patients were randomized to routine care versus high-intensity care (HIC) with rapid GDMT uptitration (beta-blockers, angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker/angiotensin receptor/neprilysin inhibitor and mineralocorticoid antagonists) at post-discharge ambulatory visits at 1, 2, 3, and 6 weeks and 90 days. Patients in the HIC arm were titrated to one-half optimal dose at randomization and full optimal doses at week 2. Outcomes of interest included symptoms and signs of congestion at 90 days.
Results:
Prior to randomization, 47% of patients had successful decongestion and were equally distributed in both arms. At day 90, a higher proportion of patients in the HIC arm had successful decongestion (75% vs. 68%), regardless of prerandomization congestion status. All individual markers of decongestion including NT-proBNP, weight reduction, and orthopnea severity were lower in HIC arm. Patients in the HIC arm had higher use of all GDMT components and higher percentage of target dose of GDMT correlated with lower congestion score at 90 days. The mean daily loop diuretic dose in both groups was similar prerandomization but by day 90 was lower in the HIC arm. The difference did not persist until day 180. All-cause mortality and first HF rehospitalization at 180 days were lower in the HIC arm, irrespective of prerandomization congestion status.
Conclusions:
In a post hoc analysis of a randomized trial of patients hospitalized with HF, intensive uptitration of GDMT was associated with sustained decongestion at day 90 and a lower risk for all-cause mortality and first HF rehospitalization.
Perspective:
Signs and symptoms of congestion are the primary reason for hospitalization in HF patients. Loop diuretics are used for treating decongestion in these patients and are associated with symptom relief but have not correlated with sustained decongestion or reduction in HF hospitalization in several studies. Findings from this study provide evidence that rapid uptitration of GDMT for HF in the post-discharge period provides an effective and sustained strategy for maintaining decongestion.
Additional noteworthy observations from this study include the means used to achieve rapid uptitration of GDMT in hospitalized HF patients post-discharge (i.e., frequent ambulatory visits at 1, 2, 3, and 6 weeks and 90 days). Therefore, post-discharge visits in HF patients must focus on the ability to uptitrate GDMT as aggressively as possible. This is very often not achieved with management, instead focusing on weight and symptom monitoring for outpatients with a key focus on diuretic titration. Important limitations to consider include inclusion of patients who responded to initial treatment, which limits generalizability, and the usual care arm not being monitored as frequently for congestion as the HIC arm.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Heart Failure, Natriuretic Peptide, Brain, Treatment Outcome
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