Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial

Maja Cikes, Ivo Planinc, Brian Claggett, Jonathan Cunningham, Davor Milicic, Nancy Sweitzer, Michele Senni, Mauro Gori, Gerard Linssen, Sanjiv J. Shah, Milton Packer, Marc Pfeffer, Michael R. Zile, Inder Anand, Lu May Chiang, Carolyn S.P. Lam, Margaret Redfield, Akshay S. Desai, John J.V. McMurray, Scott D. Solomon

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Objectives: In this study, the authors sought to assess the relationship between AFF and outcomes, the treatment response to sacubitril/valsartan and first-detected AFF in patients with HFpEF enrolled in the PARAGON-HF trial. Background: Atrial fibrillation and flutter (AFF) are common in heart failure with preserved ejection fraction (HFpEF) and increase the risk of adverse outcomes. Methods: A total of 4,776 patients formed 3 groups: those with AFF according to electrocardiography (ECG) at enrollment (n = 1,552; 33%), those with history of AFF but without AFF on ECG at enrollment (n = 1,005; 21%), and those without history of AFF or AFF on ECG at enrollment (n = 2,219, 46%). We assessed outcomes, treatment response to sacubitril/valsartan in each group, and the risk associated with first-detected AFF in patients without any known AFF. The primary outcome was a composite of total heart failure hospitalizations and cardiovascular death. Results: History of AFF and AFF at enrollment were associated with higher risk of the primary outcome (risk ratio [RR]: 1.36 [95% CI: 1.12-1.65] and RR: 1.31 [1.11-1.54], respectively), than no AFF. Neither history of AFF nor AFF at enrollment modified the treatment effect of sacubitril/valsartan. Post randomization AFF occurred in 12% of patients without previous AFF and was associated with 2.8-fold higher risk of the primary outcome, but it was not influenced by sacubitril/valsartan. Conclusions: History of AFF and AFF on ECG at enrollment were associated with a higher risk of the primary outcome. First-detected AFF was not influenced by sacubitril/valsartan, yet it was associated with increased risk of all subsequent outcomes and may represent a potential target for future HFpEF trials. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)

Original languageEnglish (US)
Pages (from-to)336-346
Number of pages11
JournalJACC: Heart Failure
Volume10
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • atrial fibrillation
  • echocardiography
  • heart failure outcomes
  • heart failure with preserved ejection fraction
  • sacubitril/valsartan

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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