Non‐cardiac comorbidities and intensive up‐titration of oral treatment in patients recently hospitalized for heart failure: Insights from the STRONG‐HF trial

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. The impact of non‐cardiac comorbidities (NNCs) on rapid up‐titration of guideline‐directed medical therapies (GDMTs) and interactions between NNCs and treatment effect of high‐intensity care (HIC) versus usual care (UC) on the primary endpoint. Proportion of patients with 0, 1, 2 and ≥3 NCCs and the prevalence of each individual comorbidity (A). Average percentage of the optimal doses of GDMTs by number of NCCs (B). Treatment effect by number of NCCs (C), with test of interaction for the outcome. CI, confidence interval; COPD, chronic obstructive pulmonary disease; HF, heart failure; HR, hazard ratio; TIA, transient ischaemic attack.