Relationship between duration of heart failure, patient characteristics, outcomes, and effect of therapy in PARADIGM-HF.

Aims: Little is known about patient characteristics, outcomes, and the effect of treatment in relation to duration of heart failure (HF). We have investigated these questions in PARADIGM-HF. The aim of the study was to compare patient characteristics, outcomes, and the effect of sacubitril/valsartan, compared with enalapril, in relation to time from HF diagnosis in PARADIGM-HF.

Methods And Results: HF duration was categorized as 0-1, >1-2, >2-5, and >5 years. Outcomes were adjusted for prognostic variables, including N-terminal pro-brain natriuretic peptide (NT-proBNP). The primary endpoint was the composite of HF hospitalization or cardiovascular death. The number of patients in each group was as follows: 0-1 year, 2523 (30%); >1-2 years, 1178 (14%); >2-5 years, 2054 (24.5%); and >5 years, 2644 (31.5%). Patients with longer-duration HF were older, more often male, and had worse New York Heart Association class and quality of life, more co-morbidity, and higher troponin-T but similar NT-proBNP levels. The primary outcome rate (per 100 person-years) increased with HF duration: 0-1 year, 8.4 [95% confidence interval (CI) 7.6-9.2]; >1-2 years, 11.2 (10.0-12.7); >2-5 years, 13.4 (12.4-14.6); and >5 years, 14.2 (13.2-15.2); P < 0.001. The hazard ratio was 1.26 (95% CI 1.07-1.48), 1.52 (1.33-1.74), and 1.53 (1.33-1.75), respectively, for >1-2, >2-5, and >5 years, compared with 0-1 year. The benefit of sacubitril/valsartan was consistent across HF duration for all outcomes, with the primary endpoint hazard ratio 0.80 (95% CI 0.67-0.97) for 0-1 year and 0.73 (0.63-0.84) in the >5 year group. For the primary outcome, the number needed to treat for >5 years was 18, compared with 29 for 0-1 year.

Conclusions: Patients with longer-duration HF had more co-morbidity, worse quality of life, and higher rates of HF hospitalization and death. The benefit of a neprilysin inhibitor was consistent, irrespective of HF duration. Switching to sacubitril/valsartan had substantial benefits, even in patients with long-standing HF.