Troponin-T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) represented important cardiac biomarkers that may offer value for predicting the risk of bleeding and mortality in patients with atrial fibrillation (AF), according to a study published in Circulation.
In this secondary analysis of the double-blind Apixaban for the Prevention of Stroke in Subjects with Atrial Fibrillation (ARISTOTLE; ClinicalTrials.gov Identifier: NCT00412984) trial, researchers sought to determine associations between changes in cardiac biomarkers with mortality and bleeding events.
A total of 14,798 patients with AF who received either apixaban or warfarin from the ARISTOTLE trial were included in the analysis. At baseline, patients had ≥1 CHADS2 risk factor for systemic embolism (SE) or stroke and also presented with one or more of four cardiac biomarkers, including troponin-T, NT-proBNP, GDF-15, and interleukin-6.
The primary end point for the analysis was cause-specific cardiovascular death, which included sudden cardiac death, heart failure death, and stroke/SE death.
Mortality occurred in 7.3% (n=1075) of patients in the cohort with available biomarker data. Patients randomly assigned to apixaban had a significantly lower risk for stroke and SE-related mortality compared with patients assigned to warfarin (39 vs 67; hazard ratio [HR], 0.58; 95% CI, 0.39-0.86; P =.005).
In terms of clinical variables, a history of heart failure was linked to an increased risk for cardiovascular death (adjusted HR, 2.05; 95% CI, 1.74-2.42; P <.0001), heart failure death (HR, 2.89; 95% CI, 2.09-3.99; P <.0001), and sudden cardiac death (HR, 2.32; 95% CI, 1.64-3.28; P <.0001). In addition, a history of stroke/SE was associated with stroke/SE-related death (HR, 2.66, 95% CI, 1.79-3.95; P <.0001).
A doubling of the troponin-T biomarker demonstrated the strongest association with sudden death in patients with AF (HR, 1.48; P <.001). In addition, GDF-15 and NT-proBNP were most associated with bleeding-related death (HR, 1.72; P =.028) and heart failure death (HR, 1.62; P <.001), respectively.
The post hoc analysis investigators suggested that the patient population of this trial may not be representative of other patients with AF receiving anticoagulation therapy.
Cardiac biomarkers, including troponin-T, NT-proBNP, GDF-15, and interleukin-6, may be useful for guiding therapies focused “on the prevention of other fatal events … and targeting treatment and prevention of cardiac risk factors such as heart failure that might improve survival of these patients.”
Disclosures: Several authors report financial relationships with pharmaceutical companies, including AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Roche, and others.
Sharma A, Hijazi Z, Andersson U, et al. The use of biomarkers to predict specific causes of death in patients with atrial fibrillation: insights from the ARISTOTLE trial [published online June 5, 2018]. Circulation. doi: 10.1161/CIRCULATIONAHA.118.034125