Systolic Blood Pressure in HFpEF Treated With Sacubitril/Valsartan

Study Questions:

What is the optimal achieved systolic blood pressure (SBP) for patients with heart failure and preserved ejection fraction (HFpEF), and are the treatment effects of sacubitril/valsartan on outcomes related to BP lowering, particularly among women who derive greater benefit from sacubitril/valsartan?


The investigators related baseline and time-updated mean achieved SBP quartiles (<120, 120-129, 130-139, ≥140 mm Hg) to the primary outcome (cardiovascular death and total HF hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome using 4,795 trial participants. 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.


Average age was 73 ± 8 years, and 52% of participants were women. After multivariable adjustment, baseline and mean achieved SBP of 120-129 mm Hg demonstrated the lowest risk for all outcomes. Sacubitril/valsartan reduced SBP by 5.2 mm Hg (95% confidence interval, 4.4-6.0) 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.


The authors concluded that 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.


This post hoc analysis of the PARAGON-HF trial reports that the treatment effect of sacubitril/valsartan was not modified by baseline SBP and was independent of change in SBP, regardless of sex. These data provide new insight into the relationship of baseline and mean achieved SBP and outcomes in HFpEF, and further suggest that SBP reduction with sacubitril/ valsartan was not responsible for its treatment benefits in HFpEF in both women and men. Given these data, additional research is indicated to elucidate the mechanisms responsible for the treatment benefits of sacubitril/valsartan.

Clinical Topics: Anticoagulation Management, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: ACC Annual Scientific Session, acc20, Blood Pressure, Geriatrics, Heart Failure, Myocardial Infarction, Natriuretic Peptide, Brain, Peptide Fragments, Stroke, Stroke Volume, Systole, Secondary Prevention, Treatment Outcome

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