6/29/23, 1:34 AM PARADIGM-HF Pathway Feedback Search Clinical Topics Home Studies PARADIGM HF PARADIGM HF Disease Heart failure 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 N = 8442 78.0% male 8442 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 systolic BP 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 Death from cardiovascular causes or hospitalization for heart failure https://web.pathway.md/studies/recTMrSbLsQB8uM3l 1/2 6/29/23, 1:34 AM PARADIGM-HF Pathway 26.5 % 26.5 21.8 19.9 % 13.3 % Significant decrease 6.6 % NNT = 21 0.0 % Sacubitril/valsartan Enalapril Significant decrease in death from cardiovascular causes 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 cardiovascular 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 death from cardiovascular causes 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. Open reference URL https://web.pathway.md/studies/recTMrSbLsQB8uM3l 2/2