STRONG-HF: High-Intensity Care Leads to Higher Doses of Guideline Heart Failure Therapy


Conclusions could not be made regarding whether lower risk was associated with improvement in heart failure or if the success of optimal medications led to better clinical outcomes.

In the post-hoc analysis of the STRONG-HF clinical trial, the patients who were assigned to high-intensity care achieved higher doses of heart failure (HF) guideline-directed medical therapy (GDMT) 2 weeks after discharge and this treatment was feasible and safe, according to results published in the JAMA Cardiology.

According to the study authors, intensive strategies of rapid up-titration of GDMT and close follow-up for care of acute HF (AHF) demonstrated safety, reductions in risk of 180-day all-cause death, or HF readmission. Even with the recommendations, investigators found that the GDMT was not up-titrated to 100% of the maximum recommended dose at 2 weeks for all individuals. They aimed to assess the association between the level of up-titration of GDMT and outcomes in a post-hoc secondary analysis.

The STRONG-HF trial included individuals who were admitted to the hospital for AHF within 72 hours before screening. To be eligible, individuals were prescribed either: one-half or less of the optimal dose of renin-angiotensin receptor system inhibitors (RASi), no β-blockers (BB), and one-half or less of the optimal dose of mineralocorticoid receptor antagonists (MRA); or no RASi, one-half or less of the optimal dose of BB, or one-half or less of the optimal dose of MRA, according to the study authors.

About the STRONG-HF Trial

Trial Name: Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies ID: NCT03412201

Sponsor: Heart Initiative

Study Estimated Completion: October 2021

Individuals who were assigned to high-intensity care had follow-up visits at 1, 2, 3, and 6 weeks, with another study visit at day 90, according to the investigators. Those who were in the usual care group followed up after the discharge date according to local practice requirements and evaluated again at day 90 after randomization. Both groups were contacted again at day 180.

In the intervention group, medications were up-titrated to one-half the optimal dose at randomization date and then full optimal doses at week 2, as long as it was safe to do so, according to the study authors. If safety indicators caused a delay in up-titration, the safety visit was required 1 week after up-titration. The primary endpoint included first HF rehospitalization or all-cause death at day 180, while secondary endpoints included EQ-5D visual analog scale score from baseline to 90 days, 180-days all-cause death, and first HF rehospitalization or all-cause death at 90 days, the study authors said.

A total of 515 individuals, with a mean age of 62.7 years and 60.4% male, were assigned to the high intensity care group. At week 2, 7.6% individuals achieved low doses, 49.3% achieved medium doses, and 43.1% achieved high doses. The study authors reported that individuals who had lower blood pressure and more congestion were less likely to be uptitrated at week 2. Further, investigators found that an increase of 10% in the average percentage optimal dose was associated with a reduction in 180-days HF readmission or all-cause death. It was also associated with a decrease in 180-day all-cause mortality. The quality of life at 90 days was improved for those who were treated with higher doses of GDMT, according to the study authors.

Adverse events at 90 days were less frequent for individuals in the high-intensity care group and higher prescribed GDMT group at week 2, according to the study authors.

Further, investigators noted that the optimization of HF therapies did not increase the risk of safety issues for individuals who received 90% or more of JF medication administration. They also added that it was difficult to determine if lower risk was associated with improvement in condition or if the success of optimal medications led to their better clinical outcome.


Cotter G, Deniau B, Davison B, Edwards C, et al. Optimization of Evidence-Based Heart Failure Medications After an Acute Heart Failure Admission: A Secondary Analysis of the STRONG-HF Randomized Clinical Trial. JAMA Cardiol. 2023. doi:10.1001/jamacardio.2023.4553

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