Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation: Insights from ARISTOTLE and RE-LY trials.

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Aulin, JuliaUppsala universitet,Institutionen för medicinska vetenskaper,Uppsala kliniska forskningscentrum (UCR) (author)

Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation : Insights from ARISTOTLE and RE-LY trials.

Article/chapterEnglish2020

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Elsevier BV,2020
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LIBRIS-ID:oai:DiVA.org:uu-430329
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-430329URI
https://doi.org/10.1111/jth.14947DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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BACKGROUND: The inflammatory biomarker interleukin-6 (IL-6) is associated with mortality in atrial fibrillation (AF).OBJECTIVE: To investigate if repeated IL-6 measurements improve the prognostication for stroke or systemic embolism, major bleeding, and mortality in anticoagulated patients with AF.METHODS: IL-6 levels by ELISA were measured at study entry and at 2 months in 4830 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial with 1.8 years median follow-up. In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, IL-6 was measured at study entry, 3, 6, and 12 months in 2559 patients with 2.0 years median follow-up. Associations between a second IL-6 measurement and outcomes, adjusted for baseline IL-6, clinical variables, and other cardiovascular biomarkers, were analyzed by Cox regression.RESULTS: Median IL-6 levels were 2.0 ng/L (interquartile range [IQR] 1.30-3.20) and 2.10 ng/L (IQR 1.40-3.40) at the two time-points in ARISTOTLE, and, in RE-LY, 2.5 ng/L (IQR 1.6-4.3), 2.5 ng/L (IQR 1.6-4.2), 2.4 ng/L (IQR 1.6, 3.9), and 2.4 ng/L (IQR 1.5, 3.9), respectively. IL-6 was associated with mortality; hazard ratios per 50% higher IL-6 at 2 or 3 months, respectively, were 1.32 (95% confidence interval, 1.23-1.41; P < .0001) in ARISTOTLE, and 1.11 (1.01-1.22, P = .0290) in RE-LY; with improved C index from 0.74 to 0.76 in ARISTOTLE, but not in the smaller RE-LY cohort. There were no consistent associations with second IL-6 and stroke or systemic embolism, or major bleeding.CONCLUSIONS: Persistent systemic inflammatory activity, assessed by repeated IL-6 measurements, is associated with mortality independent of established clinical risk factors and other strong cardiovascular biomarkers in anticoagulated patients with AF.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
anticoagulants
atrial fibrillation
inflammation
interleukin-6
mortality
stroke

Added entries (persons, corporate bodies, meetings, titles ...)

Hijazi, ZiadUppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi(Swepub:uu)ziahi940 (author)
Siegbahn, Agneta,1947-Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Klinisk kemi,UCR(Swepub:uu)agsie424 (author)
Andersson, UlrikaUppsala universitet,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)ulran224 (author)
Alexander, John H (author)
Connolly, Stuart J (author)
Ezekowitz, Michael D (author)
Gersh, Bernard J (author)
Granger, Christopher B (author)
Horowitz, John (author)
Hylek, Elaine M (author)
Lopes, Renato D (author)
Yusuf, Salim (author)
Wallentin, Lars,1943-Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),UCR(Swepub:uu)larswall (author)
Oldgren, Jonas,1964-Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi(Swepub:uu)jonaoldg (author)
Uppsala universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)

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