Key result
Higher baseline IL-6 (Q4 vs Q1) was significantly associated with increased all-cause mortality in anticoagulated patients with atrial fibrillation (HR 1.93; 95% CI 1.57-2.37).
Why the study?
Do elevated baseline inflammatory biomarkers (IL-6 and CRP) predict cardiovascular events and mortality in anticoagulated patients with atrial fibrillation?
RCT (n=14,954)
Do elevated baseline inflammatory biomarkers (IL-6 and CRP) predict cardiovascular events and mortality in anticoagulated patients with atrial fibrillation?
Hazard Ratio: 1.93 (95% CI 1.57–2.37)
In anticoagulated patients with atrial fibrillation, elevated baseline inflammatory biomarkers (IL-6 and CRP) independently predict all-cause mortality but do not improve risk prediction for stroke or major bleeding.
May refine mortality prognostication in anticoagulated AF; hypothesis-generating and does not improve stroke or bleeding prediction.
OBJECTIVE: Atrial fibrillation (AF) is a risk factor for stroke and mortality and the prothrombotic state has been linked to inflammation. In this study we evaluated the relationship between inflammatory biomarkers at baseline and future risk of cardiovascular events in the Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. METHODS: The ARISTOTLE trial randomised 18,201 patients with AF to apixaban or warfarin. Interleukin 6 (IL-6) and C reactive protein (CRP) were analysed in plasma obtained at randomisation from 14,954 participants, and median follow-up was 1.9 years. Association between quartile groups of IL-6 and CRP and outcomes were analysed by Cox regression adjusted for clinical risk factors and other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). RESULTS: The IL-6 median level was 2.3 ng/L (IQR 1.5-3.9), median CRP level was 2.2 mg/L (1.0-4.8). IL-6 and CRP were significantly associated with all-cause mortality independent of clinical risk factors and other biomarkers (HR (95% CI) 1.93 (1.57 to 2.37) and 1.49 (1.24 to 1.79), respectively, Q4 vs Q1). IL-6 was associated with myocardial infarction, cardiovascular mortality, and major bleeding beyond clinical risk factors but not in the presence of cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). Neither inflammatory biomarker was associated with stroke/systemic embolism. Risk prediction for stroke, death and major bleeding was not improved by IL-6 or CRP when added to clinical risk factors and the other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). CONCLUSIONS: In patients with AF on anticoagulation, after accounting for clinical risk factors and other biomarkers, biomarkers of inflammation were significantly associated with an increased risk of mortality. However, there were no associations with the risk of stroke or major bleeding. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT00412984 post-results.
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Hijazi et al. (2016) conducted an RCT in Atrial fibrillation (n=14,954). High IL-6 and CRP levels (Quartile 4) vs. Low IL-6 and CRP levels (Quartile 1) was evaluated on all-cause mortality (HR 1.93, 95% CI 1.57-2.37). Higher baseline IL-6 (Q4 vs Q1) was significantly associated with increased all-cause mortality in anticoagulated patients with atrial fibrillation (HR 1.93; 95% CI 1.57-2.37).
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