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J Am Coll Cardiol. 2017 Jan 31;69(4):409-419. doi: 10.1016/j.jacc.2016.10.069.

Insulin-Requiring Versus Noninsulin-Requiring Diabetes and Thromboembolic Risk in Patients With Atrial Fibrillation: PREFER in AF.

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Department of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Rome, Italy. Electronic address:
Daiichi-Sankyo Europe, Munich, Germany.
Department of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Rome, Italy.
G. d'Annunzio University of Chieti, Chieti, Italy.
Institute of Informatics, Academy of Sciences of Czech Republic, Prague, Czech Republic.
Daiichi-Sankyo Italy, Rome, Italy.
Cardiology and Arrhythmology, Georges Pompidou Hospital, René Descartes University, Paris, France.
Department of Cardiology, University Hospital Ramòn y Cajal, Madrid, Spain.
Institute of Cardiovascular Sciences, University of Birmingham and Sandwell and West Birmingham Hospitals and University Hospitals Birmingham NHS Trust, Birmingham, United Kingdom; Hospital of the University of Münster, Münster, Germany.
G. d'Annunzio University of Chieti, Chieti, Italy; Fondazione G. Monasterio, Pisa, Italy. Electronic address:



Diabetes is a known risk predictor for thromboembolic events in patients with atrial fibrillation (AF), but no study has explored the prognostic weight of insulin in this setting.


This study evaluated the differential role of insulin versus no insulin therapy on thromboembolic risk in patients with diabetes and AF.


We accessed individual patient data from the prospective, real-world, multicenter, PREFER in AF (European Prevention of thromboembolic events-European Registry in Atrial Fibrillation). We compared the rates of stroke/systemic embolism at 1 year according to diabetes status (no diabetes, diabetes without insulin therapy, diabetes on insulin therapy).


In an overall population of 5,717 patients, 1,288 had diabetes, 22.4% of whom were on insulin. For patients with diabetes who were on insulin, there was a significantly increased risk of stroke/systemic embolism at 1 year versus either no diabetes (5.2% vs. 1.9%; hazard ratio: 2.89; 95% confidence interval: 1.67 to 5.02; p = 0.0002) or diabetes without insulin treatment (5.2% vs. 1.8%; hazard ratio: 2.96; 95% confidence interval: 1.49 to 5.87; p = 0.0019). Notably, rates of stroke/embolism were similar in patients with diabetes not receiving insulin versus patients without diabetes (hazard ratio: 0.97; 95% confidence interval: 0.58 to 1.61; p = 0.90). The selective predictive role of insulin-requiring diabetes was independent of potential confounders, including diabetes duration, and was maintained in various subpopulations, including the subgroup receiving anticoagulant therapy.


In this cohort of anticoagulated patients with AF, the sole presence of diabetes not requiring insulin did not imply an increased thromboembolic risk. Conversely, insulin-requiring diabetes contributed most, if not exclusively, to the overall increase of thromboembolic risk in AF.


CHA(2)DS(2)-VASc score; registry; risk prediction; stroke; systemic embolism

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