Physicians' Academy for Cardiovascular Education

Atrial fibrillation or flutter increases risk of adverse outcomes in HFpEF

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

Literature - Cikes M, Planinc I, Claggett B, et al. - JACC Heart Fail. 2022 May;10(5):336-346. doi: 10.1016/j.jchf.2022.01.018

Introduction and methods


Atrial fibrillation and flutter (AFF) are common in patients with HFpEF and increase the risk of adverse outcomes [1]. In a post-hoc analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) study, AFF at enrollment was linked to elevated risk of CV death or HF hospitalization [2].

Aim of the study

In a post-hoc analysis of the PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial, the authors assessed the relationship between AFF status at baseline and outcomes, whether AFF modified the sacubitril/valsartan treatment effect, and whether sacubitril/valsartan influenced the development of new AFF after randomization in patients without a history of AFF.


The PARAGON-HF trial was a multinational, double-blind, phase 3 RCT in which 4822 HFpEF patients were randomized to either sacubitril/valsartan or valsartan [3].

For the current analysis, 4776 patients with baseline AFF data were divided into three groups: (1) patients with AFF based on ECG at enrollment (n = 1552; 33%); (2) those with history of AFF but no AFF on ECG at enrollment (n = 1005; 21%); and (3) those with neither history of AFF nor AFF on ECG at enrollment (n = 2219, 46%). The median follow-up time was 2.9 years (IQR: 2.5–3.4).


The primary endpoint of the PARAGON-HF trial was a composite outcome of total HF hospitalizations and CV death. Additional endpoints were first occurrence of the primary composite endpoint—first HF hospitalization and CV death (time to first outcome)—and its component first HF hospitalization, as well as all-cause mortality and nonfatal stroke.

Main results

Baseline characteristics

Relationship between AFF and outcomes

Influence of AFF on sacubitril/valsartan treatment effect

New AFF after randomization


In HFpEF patients, AFF was associated with increased risk of HF hospitalization or CV death, which was not influenced by treatment with sacubitril/valsartan. As the same was true for first-detected AFF, the authors think therapeutic trials to reduce AF burden in HFpEF patients may be warranted.


Show references

Find this article online at JACC Heart Fail.

Share this page with your colleagues and friends: