Key result
SBP ≥140 mmHg linked to ~54% higher major event risk in HFpEF versus 120-129 mmHg.
Why the study?
Guidelines recommend targeting systolic blood pressure <130 mm Hg in HFpEF despite limited data, leaving the optimal achieved SBP and whether sacubitril/valsartan's benefits are related to BP lowering uncertain.
Does sacubitril/valsartan improve outcomes independently of its blood pressure-lowering effects in patients with HFpEF?
RCT (n=4,795)
double-blind
randomized
Yes
Does sacubitril/valsartan improve outcomes independently of its blood pressure-lowering effects in patients with HFpEF?
Effect estimate: HR 1.54 (95% CI 1.24-1.91)
In patients with HFpEF, an achieved SBP of 120-129 mm Hg is associated with the lowest risk of adverse outcomes, and the clinical benefits of sacubitril/valsartan are independent of its blood pressure-lowering effects.
Sacubitril/valsartan benefits in HFpEF were unmodified by baseline SBP; leaves open whether effects are BP-independent.
Background: Guidelines recommend targeting systolic blood pressure (SBP) <130 mm Hg in heart failure with preserved ejection fraction (HFpEF) with limited data. Objectives: This study sought to determine the optimal achieved SBP and whether the treatment effects of sacubitril/valsartan on outcomes are related to BP lowering, particularly among women who derive greater benefit from sacubitril/valsartan. Methods: Using 4,795 trial participants, this study related baseline and time-updated mean achieved SBP quartiles (<120, 120 to 129, 130 to 139, ≥140 mm Hg) to the primary outcome (cardiovascular death and total heart failure hospitalizations), its components, myocardial infarction or stroke, and a renal composite outcome. At the 16-week visit, the study assessed the relationship between SBP change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The study analyzed whether the BP-lowering effects of sacubitril/valsartan accounted for its treatment effects. Results: Average age was 73 ± 8 years, and 52% of participants were women. After multivariable adjustment, baseline and mean achieved SBP of 120 to 129 mm Hg demonstrated the lowest risk for all outcomes. Sacubitril/valsartan reduced SBP by 5.2 mm Hg (95% confidence interval: 4.4 to 6.0) compared with valsartan at 4 weeks, which was not modified by baseline SBP. However, sacubitril/valsartan reduced SBP more in women (6.3 mm Hg) than men (4.0 mm Hg) (interaction p = 0.005). Change in SBP was directly associated with change in NT-proBNP (p < 0.001) but not KCCQ-OSS (p = 0.40). The association between sacubitril/valsartan and the primary outcome was not modified by baseline SBP (interaction p = 0.50) and was similar when adjusting for time-updated SBP, regardless of sex. Conclusions: Baseline and mean achieved SBP of 120 to 129 mm Hg identified the lowest risk patients with HFpEF. Baseline SBP did not modify the treatment effect of sacubitril/valsartan, and the BP-lowering effects of sacubitril/valsartan did not account for its effects on outcomes, regardless of sex.
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Selvaraj et al. (2020) conducted an RCT in Heart Failure with Preserved Ejection Fraction (HFpEF) (n=4,795). Sacubitril/valsartan vs. Valsartan was evaluated on Primary composite outcome (cardiovascular death and total HF hospitalizations) for baseline SBP ≥140 mmHg compared to 120-129 mmHg (HR 1.54, 95% CI 1.24-1.91). Baseline and mean achieved systolic blood pressure of 120-129 mmHg was associated with the lowest risk for cardiovascular death and heart failure hospitalization in patients with HFpEF, while sacubitril/valsartan reduced SBP by 5.2 mmHg compared to valsartan.