Stroke and bleeding in atrial fibrillation with chronic kidney disease

N Engl J Med. 2012 Aug 16;367(7):625-35. doi: 10.1056/NEJMoa1105594.

Abstract

Background: Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions.

Methods: Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non-end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease.

Results: Of 132,372 patients included in the analysis, 3587 (2.7%) had non-end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non-end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non-end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both.

Conclusions: Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / adverse effects*
  • Aspirin / therapeutic use
  • Atrial Fibrillation / complications*
  • Atrial Fibrillation / drug therapy
  • Female
  • Hematologic Agents / adverse effects*
  • Hematologic Agents / therapeutic use
  • Hemorrhage / etiology*
  • Humans
  • Kidney Failure, Chronic / complications
  • Male
  • Myocardial Infarction / etiology
  • Proportional Hazards Models
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / therapy
  • Renal Replacement Therapy
  • Risk
  • Stroke / etiology*
  • Thromboembolism / prevention & control
  • Warfarin / adverse effects*
  • Warfarin / therapeutic use

Substances

  • Hematologic Agents
  • Warfarin
  • Aspirin