Non-Cardiac Comorbidities and Intensive Up-Titration of Oral Treatment in Patients Recently Hospitalized for Heart Failure: Insights from the STRONG-HF Trial
Ovidiu Chioncel, Beth A. Davison, Marianna Adamo, Laura Antohi, Mattia Arrigo, Marianela Barros, Jan Biegus, Kamilė Čerlinskaitė‐Bajorė, Jelena Čelutkienė, Alain Cohen‐Solal, Albertino Damasceno, Rafael Díaz, Christopher Edwards, Gerasimos Filippatos, Antoine Kimmoun, Carolyn S.P. Lam, Marco Metra, Maria Novosadova, Matteo Pagnesi, Peter S. Pang, Piotr Ponikowski, Razvan I. Radu, Hadiza Saidu, Karen Sliwa, Adriaan A. Voors, Koji Takagi, Jozine M. ter Maaten, Daniela Tomasoni, Gad Cotter, Alexandre Mebazaa
Abstract
AIMS: To assess the potential interaction between non-cardiac comorbidities (NCCs) and the efficacy and safety of high-intensity care (HIC) versus usual care (UC) in the STRONG-HF trial, including stable patients with improved but still elevated natriuretic peptides. METHODS AND RESULTS: In the trial, eight NCCs were reported: anaemia, diabetes, renal dysfunction, severe liver disease, chronic obstructive pulmonary disease/asthma, stroke/transient ischaemic attack, psychiatric/neurological disorders, and malignancies. Patients were classified by NCC number (0, 1, 2 and ≥3). The treatment effect of HIC versus UC on the primary endpoint, 180-day death or heart failure (HF) rehospitalization, was compared by NCC number and by each individual comorbidity. Among the 1078 patients, the prevalence of 0, 1, 2 and ≥3 NCCs was 24.3%, 39.8%, 24.5% and 11.4%, respectively. Achievement of full doses of HF therapies at 90 and 180 days in the HIC was similar irrespective of NCC number. In HIC, the primary endpoint occurred in 10.0%, 16.6%, 13.6% and 26.2%, in those with 0, 1, 2 and ≥3 NCCs, respectively, as compared to 19.1%, 25.4%, 23.3% and 26.2% in UC (interaction-p = 0.80). The treatment benefit of HIC versus UC on the primary endpoint did not differ significantly by each individual comorbidity. There was no significant treatment interaction by NCC number in quality-of-life improvement (p = 0.98) or the incidence of serious adverse events (p = 0.11). CONCLUSIONS: In the STRONG-HF trial, NCCs neither limited the rapid up-titration of HF therapies, nor attenuated the benefit of HIC on the primary endpoint. In the context of a clinical trial, the benefit-risk ratio favours the rapid up-titration of HF therapies even in patients with multiple NCCs.