Physicians' Academy for Cardiovascular Education

SBP of 120-129 mmHg associated with lowest risk of outcomes in HFpEF

Systolic Blood Pressure in Heart Failure With Preserved Ejection Fraction Treated With Sacubitril/Valsartan

Literature - Selvaraj S, Claggett BL, Böhm M et al., - J Am Coll Cardiol. 2020 doi: 10.1016/j.jacc.2020.02.009.

Introduction and methods

Hypertension is common in patients with heart failure with preserved ejection fraction (HFpEF) and can lead to left ventricular hypertrophy, diastolic dysfunction, abnormal ventricular arterial coupling, and end-organ damage. It has been presumed that blood pressure (BP) control could be related to improved outcomes [1-3]. Society guidelines recommend a systolic BP (SBP) of <130 mmHg in patients with HFpEF [4,5]. There is, however, little evidence that supports this recommendation. It has remained unclear to which extend SBP control influences clinical outcomes. Furthermore, it is not known whether BP lowering is associated with clinical benefit and the relationship between BP reduction and biomarkers in HFpEF is not well established. This study assessed the prognostic role of baseline SBP and mean achieved SBP in patients with HFpEF in PARAGON-HF. Moreover, the relationship between SBP reduction with clinical outcomes and biomarkers was investigated, and it was assessed whether the treatment effect of sacubitril/valsartan was mediated by SBP reduction.

PARAGON-HF was a randomized, double-blind, parallel group, event-driven trial that investigated the efficacy and safety of sacubitril/valsartan vs valsartan in patients with HFpEF [1]. In this study data from 4,795 trial participants (average age was 73 ± 8 years, 52% were women, 82% were white) were analyzed. The primary composite outcome of this analysis was total (first and recurrent) hospitalizations for HF, and CV death. Other efficacy outcomes included CV death, total HF hospitalizations, myocardial infarction or stroke, all-cause mortality, and a renal composite outcome (decrease in eGFR of ≥50%, development of end stage renal disease, or death due to renal failure). The safety outcome was dose reduction or discontinuation. Baseline SBP and mean achieved SBP were grouped by quartiles (quartile 1: <120 mmHg; quartile 2: 120 to 129 mmHg; quartile 3: 130 to 139 mmHg; quartile 4: ≥140 mmHg). In addition, quality of life (using the overall summary score on the Kansas City Cardiomyopathy Questionnaire [KCCQ-OSS]), NT-proBNP, and high-sensitivity troponin T were assessed in a subgroup of participants with available data.

Main results


Baseline and mean achieved SBP of 120 to 129 mmHg were associated with the lowest risk of adverse outcomes in patients with HFpEF. Sacubitril/valsartan reduced SBP by 5.2 mmHg (95%CI 4.4-6.0), compared with valsartan at 4 weeks and the SBP-lowering effect was higher in women than in men. SBP-lowering was associated with a modest reduction in NT-proBNP. The BP-lowering effect of sacubitril/valsartan did not account for the treatment effects on outcomes.


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