Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation.

Abstract

BACKGROUND:

Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown.

METHODS:

The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death.

RESULTS:

In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P<0.001), NT-proBNP with heart failure death (HR, 1.62; P<0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P>0.001) followed by troponin T (HR, 1.45; P<0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death.

CONCLUSIONS:

Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation.

CLINICAL TRIAL REGISTRATION:

URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

• Authors: Abhinav Sharma, Ziad Hijazi, Ulrika Andersson, Sana M Al-Khatib, Renato D Lopes, John H Alexander, Claes Held, Elaine M Hylek, Sergio Leonardi, Michael Hanna, Justin A Ezekowitz, Agneta Siegbahn, Christopher B Granger, Lars Wallentin
• Journal: Circulation (Circulation) Vol. 138 Issue 16 Pg. 1666-1676 (10 16 2018) ISSN: 1524-4539 [Electronic] United States
• PMID: 29871978 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Biomarkers
• Factor Xa Inhibitors
• GDF15 protein, human
• Growth Differentiation Factor 15
• IL6 protein, human
• Interleukin-6
• Peptide Fragments
• Pyrazoles
• Pyridones
• Troponin T
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• apixaban
• Warfarin

Topics

• Aged
• Aged, 80 and over
• Anticoagulants (therapeutic use)
• Atrial Fibrillation (blood, diagnosis, drug therapy, mortality)
• Biomarkers (blood)
• Cause of Death
• Death, Sudden, Cardiac (epidemiology)
• Double-Blind Method
• Factor Xa Inhibitors (therapeutic use)
• Female
• Growth Differentiation Factor 15 (blood)
• Heart Failure (blood, mortality)
• Hemorrhage (blood, mortality)
• Humans
• Interleukin-6 (blood)
• Male
• Middle Aged
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• Predictive Value of Tests
• Pyrazoles (therapeutic use)
• Pyridones (therapeutic use)
• Risk Assessment
• Risk Factors
• Stroke (blood, mortality)
• Time Factors
• Treatment Outcome
• Troponin T (blood)
• Warfarin (therapeutic use)