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

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


Background: 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.

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

Methods: 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).

Results: 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.

Conclusions: 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.

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

MeSH terms

  • Aged
  • Atrial Fibrillation
  • Diabetes Complications*
  • Diabetes Mellitus, Type 1 / complications*
  • Female
  • Humans
  • Insulin / therapeutic use*
  • Male
  • Prospective Studies
  • Risk Factors
  • Thromboembolism / etiology*
  • Thromboembolism / prevention & control


  • Insulin