March 12, 2025ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam)9 citationsOpen Access
Effects of Sacubitril/Valsartan According to Natriuretic Peptide Levels in Patients Enrolled in PARADIGM-HF and PARAGON-HF
Structured PICO
Does sacubitril/valsartan reduce the composite of HF hospitalization or cardiovascular death compared to ACEi/ARB across different NT-proBNP levels in patients with heart failure?
P
Population
13,195 patients with heart failure across the range of LVEF (reduced, mildly reduced, and preserved) enrolled in PARADIGM-HF and PARAGON-HF trials, of which 13,142 had baseline NT-proBNP measured.
I
Intervention
Sacubitril/valsartan
C
Comparator
Angiotensin-converting-enzyme inhibitor (in PARADIGM-HF) or Angiotensin-receptor blocker (in PARAGON-HF)
O
Outcome
Composite of HF hospitalization or cardiovascular deathcomposite
Sacubitril/valsartan provides consistent relative risk reductions for cardiovascular death or HF hospitalization across all NT-proBNP levels in heart failure patients, resulting in greater absolute benefits for those with higher baseline NT-proBNP.
Abstract
BACKGROUND: Recent trials of new heart failure (HF) treatments suggest the effect of therapy may vary by N-terminal pro-B type natriuretic peptide (NT-proBNP) level. OBJECTIVES: The authors examined the efficacy of sacubitril/valsartan according to NT-proBNP levels in patients with reduced, mildly reduced, and preserved left ventricular ejection fraction (LVEF) enrolled in PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) and PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Receptor Blockers Global Outcomes in HF with Preserved Ejection Fraction). METHODS: Individual patient data from PARADIGM-HF and PARAGON-HF were pooled and participants were divided into categories defined by quintiles of NT-proBNP level. The primary outcome examined was the composite of HF hospitalization or cardiovascular death. RESULTS: Among the 13,195 patients enrolled in both trials, 13,142 (99.6%) had a baseline NT-proBNP level measured. The rate of the primary outcome (per 100 person-years) increased with NT-proBNP levels: quintile 1, 5.9 (95% CI: 5.3-6.5); quintile 2, 7.5 (95% CI: 6.9-8.2); quintile 3, 9.0 (95% CI: 8.2-9.7); quintile 4, 12.0 (95% CI: 11.1-12.9); and quintile 5, 20.8 (95% CI: 19.6-22.2). The relative risk reduction in the primary outcome with sacubitril/valsartan was consistent across NT-proBNP levels: the HR in quintile 1 was 0.79 (95% CI: 0.65-0.96); quintile 2, 0.87 (95% CI: 0.72-1.04); quintile 3, 0.79 (95% CI: 0.66-0.93); quintile 4, 0.85 (95% CI: 0.73-0.99); and quintile 5, 0.86 (95% CI: 0.76-0.97; P for interaction = 0.86). The absolute risk reduction was greatest in NT-proBNP quintile 5; the number needed to treat for the primary outcome over the median follow-up of 31 months was 16 in quintile 5 vs 37 in quintile 1. CONCLUSIONS: The relative risk reductions with sacubitril/valsartan were consistent irrespective of NT-proBNP level in HF patients across the range of LVEF. Consequently, the absolute risk reductions were greatest in patients with higher NT-proBNP levels. (PARADIGM-HF Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial; NCT01035255; and PARAGON-HF Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Receptor Blockers Global Outcomes in HF with Preserved Ejection Fraction; NCT01920711).