Efficacy of sacubitril/valsartan on mortality in asymptomatic hypotensive HFrEF: data from the China Cardiovascular Association Database-Heart Failure Center Registry
Z Qiu, Z Li, Y Chen, J Bu, W Jin, J YangAbstract
Background
Despite guidelines recommending rapid initiation and up-titration of Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF), concerns of asymptomatic low blood pressure (BP) often limit optimization of GDMT. Hypotension is associated with worse outcomes but how this association is modified by sacubitril/valsartan (Sac/Val) remains uncertain.
Purpose
To evaluate the association between BP and mortality according to Sac/Val dose in a large real-world HFrEF population.
Methods
Data were from the China Cardiovascular Association Database-Heart Failure Center Registry, which were linked to the National Mortality Registration Information Management System by the Chinese Centre for Disease Control and Prevention. Patients with HFrEF enrolled between January 1, 2017 and December 31, 2022 from 572 hospitals across China were includeded, if they had baseline BP records, were receiving Sac/Val or no renin-angiotensin system inhibitor (RASi), and had no symptomatic hypotension. The primary outcome was all-cause mortality.
Results
Among 75,816 eligible patients (median age 66.5 years; 30.2% female; median SBP 117 [IQR 105–129] mmHg), 17,153 (22.6%), 22,564 (29.8%), 26,842 (35.4%), 9,257 (12.2%) reached 0, 0-25%, 25-49%, ≥ 50% target Sac/Val dose respectively. During a median follow-up of 21.4 months, 16,466 deaths occurred. Baseline SBP <120 mmHg was associated with increased mortality risk. However, the survival benefit of Sac/Val up-titration was preserved across SBP strata. Compared with no RASi, the adjusted hazard ratio (HR) for ≥ 50% Sac/Val dose was 0.73 (95% CI: 0.67-0.79) in patients with SBP ≥120 mmHg, and 0.52 (95% CI: 0.47-0.58) those with SBP <120 mmHg (pinteraction = 0.005). Among 32,674 patients with serial measurements, 7,611 (23.3%) reported a SBP decrease >10 mmHg with stable or increasing Sac/Val dose. Decreasing SBP was not associated with excess risk when Sac/Val dose was increased (HR: 0.80, 95% CI: 0.70-0.91), or stable (HR: 0.88, 95% CI: 0.82-0.94), compared to stable SBP with stable dose.
Conclusions
Although hypotension was associated with higher mortality, the benefit of Sac/Val was maintained (or even more pronounced) in patients with lower SBP. SBP reduction during treatment should not preclude Sac/Val dose optimization.K-M Curve Among SBP and ARNI Dose StrataARNI dose change and all-cause mortality