Key result
Low-dose sacubitril/valsartan linked to ~156% higher all-cause mortality versus the high dose.
Why the study?
Limited evidence is available regarding low (24/26 mg) and middle (49/51 mg) doses of sacubitril/valsartan on clinical outcomes in HFrEF.
Does higher dose sacubitril/valsartan improve mortality and heart failure hospitalization compared to low dose in patients with HFrEF?
Cohort (n=652)
Yes
Does higher dose sacubitril/valsartan improve mortality and heart failure hospitalization compared to low dose in patients with HFrEF?
Hazard Ratio: 2.56 (95% CI 1.54–4.24)
Absolute Event Rate: 29.63% vs 9.27%
Higher doses of sacubitril/valsartan (49/51 mg or 97/103 mg) are associated with lower rates of all-cause mortality and heart failure hospitalization compared to the low dose (24/26 mg) in patients with HFrEF.
Warrants caution with low-dose sacubitril/valsartan; hypothesis-generating for titration benefits in real-world HFrEF.
BACKGROUND: Limited evidence is available regarding low (24/26 mg) and middle (49/51 mg) doses of sacubitril/valsartan. OBJECTIVES: The purpose of this study was to investigate the effect of sacubitril/valsartan dose on heart failure (HF) hospitalization and mortality in patients with HF with reduced ejection fraction (HFrEF). METHODS: A retrospective multicenter cohort study compared 3 doses of sacubitril/valsartan in patients with HFrEF. The coprimary outcomes were all-cause mortality and rehospitalization for HF. Propensity matching analysis was performed. RESULTS: Of 721 eligible patients, propensity matching created a cohort with an effective sample size of 652 (24/26-mg group [n = 326], 49/51-mg group [n = 147], 97/103-mg group [n = 179]). The HF hospitalization rates were 29.14% in the 24/26-mg group, 19.51% in the 49/51-mg group, and 16.10% in the 97/103-mg group (24/26 vs 49/51 mg: HR = 1.56, 95% CI = 1.04-2.34; 24/26 vs 97/103 mg: HR = 1.79, 95% CI = 1.18-2.73; 49/51 vs 97/103 mg: HR = 1.15, 95% CI = 0.70-1.89). All-cause mortality rates were 29.63% in the 24/26-mg group, 17.58% in the 49/51-mg group, and 9.27% in the 97/103-mg group (24/26 vs 49/51 mg: HR = 1.67, 95% CI = 1.07-2.59; 24/26 vs 97/103 mg: HR = 2.56, 95% CI = 1.54-4.24; 49/51 vs 97/103 mg: HR = 1.54, 95% CI = 0.84-2.82). CONCLUSION AND RELEVANCE: Sacubitril/valsartan 97/103- or 49/51-mg dose is associated with a lower mortality or hospitalization rate for HF in patients receiving sacubitril/valsartan compared with the 24/26-mg dose group.
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Kido et al. (2020) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=652). Sacubitril/valsartan vs. 97/103 mg was evaluated on All-cause mortality (HR 2.56, 95% CI 1.54-4.24). Low-dose sacubitril/valsartan (24/26 mg) was associated with higher all-cause mortality compared to the 97/103 mg dose (29.63% vs 9.27%; HR 2.56, 95% CI 1.54-4.24).
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