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

Abstract

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 hospitalization), 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. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

• Authors: Senthil Selvaraj, Brian L Claggett, Michael Böhm, Stefan D Anker, Muthiah Vaduganathan, Faiez Zannad, Burkert Pieske, Carolyn S P Lam, Inder S Anand, Victor C Shi, Martin P Lefkowitz, John J V McMurray, Scott D Solomon
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 75 Issue 14 Pg. 1644-1656 (04 14 2020) ISSN: 1558-3597 [Electronic] United States
• PMID: 32192799 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Biphenyl Compounds
• Drug Combinations
• Peptide Fragments
• Tetrazoles
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• Valsartan
• Neprilysin
• sacubitril and valsartan sodium hydrate drug combination

Topics

• Aged
• Aminobutyrates (administration & dosage, adverse effects)
• Angiotensin Receptor Antagonists (administration & dosage, adverse effects)
• Biphenyl Compounds
• Blood Pressure (drug effects)
• Double-Blind Method
• Drug Combinations
• Drug Monitoring (methods)
• Female
• Heart Failure (blood, drug therapy, physiopathology)
• Humans
• Male
• Natriuretic Peptide, Brain (blood)
• Neprilysin (metabolism)
• Outcome Assessment, Health Care
• Peptide Fragments (blood)
• Sex Factors
• Stroke Volume (drug effects)
• Tetrazoles (administration & dosage, adverse effects)
• Valsartan