February 21, 2020Journal of Clinical MedicineOpen Access

Impact of the Fibrosis-4 Index on Risk Stratification of Cardiovascular Events and Mortality in Patients with Atrial Fibrillation: Findings from a Japanese Multicenter Registry

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Why the study?

The prognostic impact of using the Fibrosis-4 index to assess risk for cardiovascular events and mortality in patients with AF was unknown.

Does the FIB4 index predict cardiovascular events and mortality in patients with atrial fibrillation?

Structured PICO

Does the FIB4 index predict cardiovascular events and mortality in patients with atrial fibrillation?

Population

3,067 patients with atrial fibrillation enrolled in a multicenter Japanese registry

Intervention

High Fibrosis-4 (FIB4) index (third tertile: FIB4 index ≥ 2.51)

Comparator

Lower Fibrosis-4 (FIB4) index (first tertile: < 1.75, second tertile: 1.75 ≤ FIB4 index < 2.51)

Outcome

Cardiovascular events and all-cause mortalityhard clinical

The FIB4 index, a non-invasive marker of liver fibrosis, independently predicts cardiovascular events and all-cause mortality in patients with atrial fibrillation and improves risk stratification when added to the CHA2DS2-VASc score.

Implication

FIB4 index may refine risk stratification in AF; leaves open its added value beyond existing scores pending validation.

Abstract

Background: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. Methods: We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index < 1.75, n = 1022), second tertile (1.75 ≤ FIB4 index < 2.51, n = 1022), and third tertile (FIB4 index ≥ 2.51, n = 1023). Results: The third tertile had statistically significant results: older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p < 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p < 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72; 95% CI 1.31–2.25) and all-cause mortality (HR 1.43; 95% CI 1.06–1.95). Adding the FIB4 index to a baseline model with CHA2DS2-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p < 0.05), net reclassification improvement (all p < 0.001), and integrated discrimination improvement (all p < 0.001). A FIB4 index ≥ 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS2 scores (all p < 0.001). Conclusions: The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients.