PARAGON-HF
Trial question
What is the role of sacubitril/valsartan in HF patients with preserved ejection fraction?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
52.0% female
48.0% male
N = 4796
4796 patients (2479 female, 2317 male).
Inclusion criteria: patients with HF, ejection fraction ≥ 45%, elevated level of natriuretic peptides, and structural heart disease.
Key exclusion criteria: prior measurement of LVEF < 40%; acute coronary syndrome, cardiac surgery, other major cardiovascular surgery within 3 months; acute decompensated HF requiring therapy.
Interventions
N=2407 sacubitril/valsartan (target dose of 97 mg sacubitril with 103 mg valsartan BID).
N=2389 valsartan (target dose of 160 mg BID).
Primary outcome
Total hospitalizations for heart failure and CV death
21.9%
23.3%
23.3 %
17.5 %
11.7 %
5.8 %
0.0 %
Sacubitril/valsartan
Valsartan
No significant
difference ↔
No significant difference in total hospitalizations for HF and CV death (21.9% vs. 23.3%; RR 0.87, 95% CI 0.75 to 1.01).
Secondary outcomes
Significantly greater improvement in NYHA class at 8 months (15% vs. 12.6%; OR 1.45, 95% CI 1.13 to 1.86).
Significant decrease in death from renal failure, ESRD, or a ≥ 50% reduction in the eGFR (1.4% vs. 2.7%; HR 0.5, 95% CI 0.33 to 0.77).
No significant difference in death from any cause (14.2% vs. 14.6%; HR 0.97, 95% CI 0.84 to 1.13).
Safety outcomes
No significant difference in liver-related adverse event.
Significant differences in hypotension with SBP < 100 mmHg (15.8% vs. 10.8%), angioedema (0.6% vs. 0.2%), hyperkalemia (16.3% vs. 19.6%).
Conclusion
In patients with HF, ejection fraction ≥ 45%, elevated level of natriuretic peptides, and structural heart disease, sacubitril/valsartan was not superior to valsartan with respect to total hospitalizations for HF and CV death.
Reference
Scott D Solomon, John J V McMurray, Inder S Anand et al. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019 Oct 24;381(17):1609-1620.
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