PARADIGM-HF
Trial question
What is the role of angiotensin-neprilysin inhibition in patients with HF?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
22.0% female
78.0% male
N = 8399
8399 patients (1832 female, 6567 male).
Inclusion criteria: patients with class II, III, or IV HF and a reduced ejection fraction of ≤ 40%.
Key exclusion criteria: symptomatic hypotension, a SBP of < 95 mmHg at randomization, a serum potassium level > 5.4 mmol/L at randomization, or a history of angioedema or unacceptable side effects during receipt of ACE inhibitors or ARBs.
Interventions
N=4187 sacubitril/valsartan (at a dose of 200 mg BID plus recommended therapy).
N=4212 enalapril (at a dose of 10 mg BID plus recommended therapy).
Primary outcome
CV death or hospitalization for heart failure
21.8%
26.5%
26.5 %
19.9 %
13.3 %
6.6 %
0.0 %
Sacubitril/valsartan
Enalapril
Significant
decrease ▼
NNT = 21
Significant decrease in CV death or hospitalization for HF (21.8% vs. 26.5%; HR 0.8, 95% CI 0.73 to 0.87).
Secondary outcomes
Significant decrease in death from any cause (17% vs. 19.8%; HR 0.84, 95% CI 0.76 to 0.93).
Significant decrease in CV death (13.3% vs. 16.5%; HR 0.8, 95% CI 0.71 to 0.89).
Significant decrease in hospitalization for HF (12.8% vs. 15.6%; HR 0.79, 95% CI 0.71 to 0.89).
Safety outcomes
No significant difference in nonserious angioedema (0.2% vs. 0.1%).
Significant differences in hypotension (14.0% vs. 9.2%), cough (11.3% vs. 14.3%), hyperkalemia (4.3% vs. 5.6%) and renal impairment (0.7% vs. 1.4%).
Conclusion
In patients with class II, III, or IV HF and a reduced ejection fraction of ≤ 40%, sacubitril/valsartan was superior to enalapril with respect to CV death or hospitalization for HF.
Reference
McMurray JJ, Packer M, Desai AS et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004.
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