Results of the STRONG-HF trial confirm what many already suspected: In-hospital initiation of guideline-directed medical therapy (GDMT) significantly reduced risk of 180-day all-cause mortality and heart failure readmission.
Although many had hypothesized about the benefit of rapid initiation of GDMT in patients with heart failure, results of the STRONG-HF trial, which was stopped early on recommendations from the Data Safety Monitoring Board based on superior efficacy, provide the first evidence of the safety and efficacy of early and rapid optimization of GDMT in a randomized clinical trial.
“Patients and healthcare providers will love STRONG. Why? Because the rapid up-titration of heart failure therapies under very close follow-up, with clinic exams and NT-proBNP, is safe, it reduces heart failure readmission, all-cause death, and it markedly improved patients’ quality of life,” said lead investigator Alexandre Mebazaa, MD, PhD, chairman of the department of anesthesia and critical care at the University of Paris, during the presentation of STRONG-HF results at the American Heart Association 2022 Scientific Sessions. “The next challenge is the rapid education to implement the STRONG-HF procedure into daily practice.”
An investigator-initiated trial led by Mebazaa and colleagues from Europe and the US, STRONG-HF was designed as a randomized, multi-center, therapeutic strategy trial designed to enroll 1800 people admitted for acute heart failure and randomize them to usual care or a high-intensity care arm. Those randomized to the study’s high-intensity care arm received GDMT uptitrated to half optimal doses at discharge and to full optimal doses at 2 weeks post-discharge.
As part of the study protocol, safety visits occurred 1 week after any up-titration that occurred and follow-up visits occurring at 6 weeks and 3 months. Investigators pointed out patients were assessed by physical examination for congestion and blood tests including NT-proBNP measurements at each study visit. Although investigates planned to enroll 1800 patients in the trial, the Data Safety Monitoring Board recommended premature termination of the trial based on an assessment of data from 1000 patients with at least 90 days of follow-up.
During his AHA 22 presentation, Mebazaa provided insight into the 1078 individuals successfully randomized in the study, with 542 randomized to the high-intensity care arm and 536 randomized to usual care. This cohort, which was recruited from 87 medical centers in 14 countries, had a mean age of 63.0 (SD, 13.6) years, 39% were female, and 77% were White. Investigators pointed out randomization was stratified by LVEF and country.
As of the October 13, 2022, data cutoff, results indicated blood pressure, pulse, New York Heart Association class, body weight, and NT-proBNP concentration had decreased more in the high-intensity care group than in the usual care group by day 90. When assessing for the primary outcome of interest, results indicated heart failure readmission or all-cause death up to day 180 occurred in 74 (15.2% down-weighted adjusted Kaplan-Meier estimate) of patients randomized to the high-intensity care group and 109 (23.3%) patients in the usual care group (adjusted risk difference, 8.1% [95% CI 2.9-13.2] P=.0021; risk ratio, 0.66 [95% CI 0.50-0.86]). When assessing safety outcomes, Mebazaa noted an increased rate of adverse events at 90 days occurred in the high-intensity arm than in the usual care (41% vs 29%), but also pointed out incidences of serious adverse events (16% vs 17%) and fatal adverse events (5% vs 6%) were similar in both arms.
This study, “STRONG-HF: Successful Post-Discharge Management of Heart Failure,” was presented at AHA 22 and simultaneously published in The Lancet.