Titration of Medications After Discharge for Acute HF

Quick Takes

  • After a hospitalization for acute HF, patients benefit from an early and rapid optimization of HF therapies and close clinical follow-up despite baseline HF risk profile.
  • This strategy does not lead to increase in serious adverse events despite baseline HF risk profile, though increases in nonserious events (such as hypotension, hyperkalemia, and renal impairment) are noted.

Study Questions:

What is the safety, tolerability, and efficacy of high-intensity care (HIC) following hospital discharge for acute heart failure (HF) based on estimated clinical risk scores?


This study was a secondary analysis of the multicenter, international STRONG-HF trial, which enrolled patients admitted to the hospital with acute HF but not discharged on recommended doses of HF guideline-directed medical therapy (GDMT). The trial randomized 1,078 patients who received HIC (consisting of up-titration of GDMT to recommended doses within 2 weeks of discharge and four outpatient visits within 2 months of discharge) or usual care (UC). In the original study, the primary composite endpoint of all-cause death or first HF rehospitalization at 180 days was reduced in the HIC group compared to UC. The result was primarily driven by reduction in first HF rehospitalization. For this current analysis, outcomes were assessed after stratifying patients into tertiles based on predicted HF risk using the Meta-Analysis Global Group in Chronic (MAGGIC) risk calculator.


Of the original 1,078 patients, 1,062 (98.5%) had data available to calculate a baseline MAGGIC risk score (excluding smoking history). Based on risk scores, patients were divided in tertiles 1 (lowest HF risk), 2, and 3 (highest HF risk). Of note, HF GDMT use was similar across tertiles and percentage optimal GDMT use was higher in the HIC group compared to UC for all three tertiles.

The overall incidence of the primary composite outcome was 16.3%, 18.9%, and 23.2% for tertiles 1, 2, and 3, respectively. After adjusting for confounders, risk was not significantly different between tertiles. When compared to UC, the HIC group had reductions in the primary outcome in the overall cohort (hazard ratio, 0.66; 95% confidence interval, 0.50-0.86), which was similar between tertiles.

Rates of adverse events (including hypotension, hyperkalemia, and renal impairment) were higher in the HIC group compared to UC, which did not differ between tertiles of HF risk. Rates of serious adverse events were similar between the HIC and UC groups, which was the case across the tertiles.


After hospitalization for acute HF, HIC compared to UC led to reductions in the composite of all-cause death or first HF rehospitalization at 180 days, a finding that is similar regardless of estimated baseline HF risk.


It is well established that there is great benefit associated with HF GDMT, but getting patients on evidence-based recommended doses of these therapies has remained a challenge. The reasons for this are complex and generally are not solely due to a single clinical factor. The STRONG-HF trial addressed an aspect of this dilemma by demonstrating the value of an early and intense medication titration strategy with close clinical follow-up after hospitalization for acute HF. This approach helped to reduce the composite outcome of all-cause death or first HF rehospitalization at 180 days and was generally safe with increased rates of nonserious adverse events but similar rates of serious adverse events.

The secondary analysis carried out in this studied examined if these outcomes were similar when stratifying patients by baseline HF risk, as determined by a broadly applicable MAGGIC risk calculator. This approach was intended to capture the multifactorial nature of HF risk rather than focus on a single clinical variable (like left ventricular ejection fraction or natriuretic peptide level). In practice, a patient’s perceived level of baseline risk may affect treatment choices, such as deciding not to rapidly up-titrate medications in those at high HF risk with significant co-morbidities. It is reassuring that the results of this study demonstrated similar benefit with an HIC strategy despite baseline HF risk, giving clinicians confidence that all patients in this setting can safely benefit from early optimization of HF care. Of note, this study was conducted before the recommendations for routine SGLT2 inhibitor use in HF, so the impact of this change on the study findings is unclear.

Clinical Topics: Acute Heart Failure, Heart Failure and Cardiomyopathies

Keywords: Acute Heart Failure, Risk Assessment

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