Effects of Sacubitril/Valsartan According to Natriuretic Peptide Levels in Patients Enrolled in PARADIGM-HF and PARAGON-HF.
Total: 81.0Innovation: 7Impact: 8Rigor: 9Citation: 8
Summary
Pooling PARADIGM-HF and PARAGON-HF, sacubitril/valsartan reduced the composite of HF hospitalization or cardiovascular death consistently across NT-proBNP quintiles. Absolute benefit was largest in the highest NT-proBNP quintile (NNT 16 over 31 months), supporting risk-based prioritization.
Key Findings
- Relative risk reduction with sacubitril/valsartan was consistent across NT-proBNP quintiles (interaction P=0.86).
- Absolute risk reduction and number needed to treat were most favorable in the highest NT-proBNP quintile (NNT 16 over a median 31 months vs 37 in the lowest quintile).
- Event rates rose stepwise with NT-proBNP, enabling risk targeting without loss of relative efficacy.
Clinical Implications
Treat across NT-proBNP levels, but prioritize initiation and adherence support in patients with high NT-proBNP to maximize absolute event reduction and cost-effectiveness.
Why It Matters
Directly informs patient selection and health system allocation by showing where absolute benefit is greatest while preserving consistent relative efficacy.
Limitations
- Secondary, post hoc stratified analysis; not randomized by NT-proBNP levels
- Potential residual confounding and differences in trial populations
Future Directions
Prospective studies to test NT-proBNP–guided initiation/escalation strategies and health-economic impact assessments.
Study Information
- Study Type
- Meta-analysis
- Research Domain
- Treatment
- Evidence Level
- II - Patient-level pooled analysis from randomized controlled trials
- Study Design
- OTHER