TY - JOUR
T1 - Effects of sacubitril/valsartan according to background beta-blocker therapy in patients with heart failure and reduced ejection fraction
T2 - Insights from PARADIGM-HF
AU - Gupta, Sharmistha Datta
AU - Butt, Jawad H
AU - McMurray, Eoghan G M
AU - Talebi, Atefeh
AU - Matsumoto, Shingo
AU - Rizkala, Adel R
AU - Henderson, Alasdair D
AU - Desai, Akshay S
AU - Lefkowitz, Martin
AU - Packer, Milton
AU - Rouleau, Jean L
AU - Solomon, Scott D
AU - Swedberg, Karl
AU - Zile, Michael R
AU - Jhund, Pardeep S
AU - McMurray, John J V
AU - PARADIGM‐HF Investigators and Committees
N1 - © 2024 European Society of Cardiology.
PY - 2025/5
Y1 - 2025/5
N2 - AIMS: Beta-blockers may inhibit neprilysin activity and conversely, neprilysin inhibition may have a sympatho-inhibitory action. Consequently, sacubitril/valsartan may have a greater effect in patients not receiving a beta-blocker compared to those treated with a beta-blocker.METHODS AND RESULTS: We examined the effect of sacubitril/valsartan compared to enalapril on outcomes according to background beta-blocker treatment in the 8399 patients with heart failure with reduced ejection fraction enrolled in PARADIGM-HF. The primary outcome was time to first heart failure hospitalization or cardiovascular death. Compared to the 7811 patients taking a beta-blocker, the 588 patients not receiving a beta-blocker were older, more frequently female, but had a similar mean left ventricular ejection fraction and New York Heart Association class distribution, with little difference in N-terminal pro-B-type natriuretic peptide. Patients not taking beta-blockers had a higher rate of the primary endpoint than those taking beta-blockers. The benefit of sacubitril/valsartan on the primary endpoint was evident in both the no beta-blocker subgroup (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.45-0.82) and the beta-blocker subgroup (HR 0.82, 95% CI 0.75-0.90; p-interaction = 0.06). The respective HRs for cardiovascular death were 0.47 (95% CI 0.32-0.69) versus 0.84 (95% CI 0.75-0.95; p-interaction <0.01) and for HF hospitalization 0.76 (95% CI 0.51-1.12) versus 0.80 (95% CI 0.71-0.90; p-interaction = 0.73). For all-cause death, the HR in the no beta-blocker group was 0.50 (95% CI 0.36-0.71) compared to 0.89 (95% CI 0.80-0.99) in the beta-blocker group (p-interaction <0.01). Safety outcomes related to sacubitril/valsartan versus enalapril did not differ according to background beta-blocker use.CONCLUSION: Sacubitril/valsartan may be more effective than enalapril in reducing the risk of death in patients not treated with a beta-blocker compared to those treated with a beta-blocker, but is effective regardless of beta-blocker use.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01035255.
AB - AIMS: Beta-blockers may inhibit neprilysin activity and conversely, neprilysin inhibition may have a sympatho-inhibitory action. Consequently, sacubitril/valsartan may have a greater effect in patients not receiving a beta-blocker compared to those treated with a beta-blocker.METHODS AND RESULTS: We examined the effect of sacubitril/valsartan compared to enalapril on outcomes according to background beta-blocker treatment in the 8399 patients with heart failure with reduced ejection fraction enrolled in PARADIGM-HF. The primary outcome was time to first heart failure hospitalization or cardiovascular death. Compared to the 7811 patients taking a beta-blocker, the 588 patients not receiving a beta-blocker were older, more frequently female, but had a similar mean left ventricular ejection fraction and New York Heart Association class distribution, with little difference in N-terminal pro-B-type natriuretic peptide. Patients not taking beta-blockers had a higher rate of the primary endpoint than those taking beta-blockers. The benefit of sacubitril/valsartan on the primary endpoint was evident in both the no beta-blocker subgroup (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.45-0.82) and the beta-blocker subgroup (HR 0.82, 95% CI 0.75-0.90; p-interaction = 0.06). The respective HRs for cardiovascular death were 0.47 (95% CI 0.32-0.69) versus 0.84 (95% CI 0.75-0.95; p-interaction <0.01) and for HF hospitalization 0.76 (95% CI 0.51-1.12) versus 0.80 (95% CI 0.71-0.90; p-interaction = 0.73). For all-cause death, the HR in the no beta-blocker group was 0.50 (95% CI 0.36-0.71) compared to 0.89 (95% CI 0.80-0.99) in the beta-blocker group (p-interaction <0.01). Safety outcomes related to sacubitril/valsartan versus enalapril did not differ according to background beta-blocker use.CONCLUSION: Sacubitril/valsartan may be more effective than enalapril in reducing the risk of death in patients not treated with a beta-blocker compared to those treated with a beta-blocker, but is effective regardless of beta-blocker use.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01035255.
KW - Adrenergic beta-Antagonists/therapeutic use
KW - Aged
KW - Aminobutyrates/therapeutic use
KW - Angiotensin Receptor Antagonists/therapeutic use
KW - Biphenyl Compounds
KW - Drug Combinations
KW - Enalapril/therapeutic use
KW - Female
KW - Heart Failure/drug therapy
KW - Hospitalization/statistics & numerical data
KW - Humans
KW - Male
KW - Middle Aged
KW - Neprilysin/antagonists & inhibitors
KW - Stroke Volume/physiology
KW - Tetrazoles/therapeutic use
KW - Treatment Outcome
KW - Valsartan
UR - https://www.scopus.com/pages/publications/85210011117
U2 - 10.1002/ejhf.3515
DO - 10.1002/ejhf.3515
M3 - Journal article
C2 - 39563094
SN - 1388-9842
VL - 27
SP - 779
EP - 787
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
IS - 5
ER -