Key result
Sacubitril/valsartan consistently reduces HF hospitalization or CV death by ~20% versus enalapril across all disease durations.
Why the study?
Little was known about patient characteristics, outcomes, and the effect of treatment in relation to the duration of heart failure.
Does sacubitril/valsartan reduce the composite of HF hospitalization or cardiovascular death compared to enalapril across different durations of heart failure?
RCT (n=8,399)
Does sacubitril/valsartan reduce the composite of HF hospitalization or cardiovascular death compared to enalapril across different durations of heart failure?
Sacubitril/valsartan provides consistent cardiovascular benefits over enalapril regardless of the duration of heart failure, with higher absolute benefits in those with longer-standing disease due to higher baseline risk.
Supports consistent benefit irrespective of HF duration; leaves open randomized confirmation by chronicity.
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.
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Yeoh et al. (2020) conducted an RCT in Heart failure (n=8,399). Sacubitril/valsartan vs. Enalapril was evaluated on Composite of HF hospitalization or cardiovascular death (HR 0.80 (0-1 year), HR 0.73 (>5 years), 95% CI 0.67-0.97 (0-1 year), 0.63-0.84 (>5 years)). Sacubitril/valsartan consistently reduced the composite of HF hospitalization or cardiovascular death compared with enalapril across all HF durations (HR 0.80 for 0-1 year; HR 0.73 for >5 years).
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