Sustained atrial fibrillation increases the risk of anticoagulation-related bleeding in heart failure
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Oral anticoagulation therapy in individuals with atrial fibrillation (AF) reduces the risk of thromboembolic events at cost of an increased bleeding risk. Whether anticoagulation-related outcomes differ between patients with paroxysmal and sustained AF receiving anticoagulation is controversially discussed.
In the present analysis of the prospective multi-center cohort study thrombEVAL, the incidence of anticoagulation-related adverse events was analyzed according to the AF phenotype. Information on outcome was centrally recorded over 3 years, validated via medical records and adjudicated by an independent review panel. Study monitoring was provided by an independent institution.
Overall, the sample comprised 1089 AF individuals, of whom n = 398 had paroxysmal AF and n = 691 experienced sustained AF. In Cox regression analysis with adjustment for potential confounders, sustained AF indicated an independently elevated risk of clinically relevant bleeding compared to paroxysmal AF [hazard ratio (HR) 1.40 (1.02; 1.93); P = 0.038]. For clinically relevant bleeding, a significant interaction of the pattern of AF type with concomitant heart failure (HF) was detected: HRHF 2.45 (1.51, 3.98) vs. HRno HF 0.85 (0.55, 1.34); Pinteraction = 0.003. In HF patients, sustained AF indicated also an elevated risk of major bleeding [HR 2.25 (1.26, 4.20); P = 0.006]. A simplified HAS-BLED score incorporating only information on age (> 65 years), bleeding history, and HF with sustained AF demonstrated better discriminative performance for clinically relevant bleeding than the original version: AUCHAS-BLED: 0.583 vs. AUCsimplifiedHAS-BLED: 0.642 (P = 0.004).
In HF patients receiving oral anticoagulation, sustained AF indicates a substantially elevated risk of bleeding.
Clinical Trial Registration
https://clinicaltrials.gov, identifier: NCT01809015.
KeywordsAtrial fibrillation Anticoagulation Bleeding Heart failure
Area under the curve
Cardiovascular risk factor
Time in therapeutic range
We are indebted to all study participants of the thrombEVAL study and all co-workers of the Center for Thrombosis and Hemostasis of the University Medical Mainz. This work contains results that are a part of the doctoral thesis of Torben Knöpfler.
The thrombEVAL study was supported by the state initiative “health economy” of the Ministries of Health and Economics, Rhineland-Palatinate, Germany (Grant identifier: AZ.623-1), the Federal Ministry of Education and Research, Germany (Grant identifier: BMBF 10E01003), the Centre for Translational Vascular Biology (CTVB) of the University Medical Center Mainz, Boehringer Ingelheim Pharma GmbH & Co. KG, Bayer Vital GmbH, Daiichi Sankyo Europe GmbH, Sanofi-Aventis Germany GmbH, IMO Institute GmbH, Portavita BV and the German Heart Foundation. The sponsoring bodies played no role in the planning, conduct or analysis of this study.
Compliance with ethical standards
Conflict of interest
There are no conflicts of interest to declare.
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