Safety Indicators in Patients Receiving High-intensity Care After Hospital Admission for Acute Heart Failure: The STRONG-HF Trial
Daniela Tomasoni, Beth A. Davison, Marianna Adamo, Matteo Pagnesi, Alexandre Mebazaa, Christopher Edwards, Mattia Arrigo, Marianela Barros, Jan Biegus, Jelena Čelutkienė, Kamilė Čerlinskaitė‐Bajorė, Ovidiu Chioncel, Alain Cohen‐Solal, Albertino Damasceno, Rafael Díaz, Gerasimos Filippatos, Étienne Gayat, Antoine Kimmoun, Carolyn S.P. Lam, Maria Novosadova, Peter S. Pang, Piotr Ponikowski, Hadiza Saidu, Karen Sliwa, Koji Takagi, Jozine M. ter Maaten, Adriaan A. Voors, Gad Cotter, Marco Metra
Abstract
BackgroundSTRONG-HF demonstrated the safety and efficacy of rapid up-titration of guideline-directed medical therapy (GDMT) with high intensity care (HIC) compared to usual care in patients hospitalized for acute heart failure (HF). In the HIC group, the following safety indicators were used to guide up-titration: estimated glomerular filtration rate [eGFR] <30ml/min/1.73m2, serum potassium >5.0 mmol/L, systolic blood pressure (SBP) <95mmHg, heart rate <55bpm, NT-proBNP concentration >10% higher than pre-discharge values.MethodsWe examined the impact of protocol-specified safety indicators on achieved dose of GDMT and clinical outcomes.ResultsThree-hundred-thirteen of the 542 patients in the HIC arm (57.7%) met at least one safety indicator at any follow-up visit 1 to 6 weeks after discharge. As compared to those without, patients meeting at least one safety indicator had more severe HF symptoms, lower SBP and higher heart rate at baseline and achieved a lower average percentage of GDMT optimal doses (mean difference vs the HIC arm patients not reaching any safety indicator, -11.0% [95% CI -13.6 to -8.4%], P<0.001). The primary endpoint of 180-day all-cause death or HF re-admission occurred in 15.0% of patients with any safety indicator versus 14.2% of those without (adjusted hazard ratio [HR] 0.84, 95% CI 0.48 to 1.46, P=0.540). None of each safety indicator, considered alone, was significantly associated with the primary endpoint, but SBP < 95mmHg was associated with a trend towards increased 180 days all-cause mortality (adjusted HR = 2.68 [0.94 to 7.64]; P = 0.065) and eGFR drop to < 30ml/min/1.73m2 with more HF readmissions (adjusted HR 3.60 [1.22 to 10.60]; p = 0.0203). The occurrence of a safety indicator was associated with a smaller 90-day improvement in EQ-5D VAS (adjusted mean difference -3.32 points, 95% CI -5.97 to -0.66, P=0.015).ConclusionsAmong patients with acute HF enrolled in STRONG-HF in the HIC arm, the occurrence of any safety indicator was associated with the administration of slightly lower GDMT doses and less improvement in quality of life but with no significant increase in the primary outcome of 180-day HF readmission or death when appropriately addressed according to the study protocol.