Raffaele De Caterina1,2, Giuseppe Patti3, Johan Westerbergh4, John Horowitz5, Justin A Ezekowitz6, Basil S Lewis7, Renato D Lopes8, John J V McMurray9, Dan Atar10, M Cecilia Bahit11, Matyas Keltai12, José L López-Sendón13, Witold Ruzyllo14, Christopher B Granger8, John H Alexander8, Lars Wallentin4,15. 1. Chair of Cardiology, University of Pisa, and Cardiovascular Division, Pisa University Hospital, Via Paradisa 2, 56126 Pisa, Italy. 2. Fondazione Villa Serena per la Ricerca, Città Sant'Angelo, Italy. 3. University of East Piedmont, Novara, Italy. 4. Uppsala Clinical Research Center, Uppsala University, Dag Hammarskjölds väg 38, 751 85 Uppsala, Sweden. 5. University of Adelaide, Adelaide, SA, Australia. 6. University of Alberta, Edmonton, Canada. 7. Lady Davis Carmel Medical Center, Haifa, Israel. 8. Duke Clinical Research Institute, Duke Medicine, Durham, NC, USA. 9. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. 10. Department of Cardiology, Oslo University Hospital Ulleval and Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, Oslo, Norway. 11. INECO Neurociencias Oroño, Fundación INECO, Rosario, Argentina. 12. Hungarian Institute of Cardiology, Semmelweis University, Budapest, Hungary. 13. Hospital Universitario La Paz, UAM, Idipaz, CIBER-CV, Madrid, Spain. 14. Institute of Cardiology, Warsaw, Poland. 15. Department of Medical Sciences, Cardiology, Uppsala University, Uppsala University Hospital ingång 40, 751 85 Uppsala, Sweden.
Abstract
AIMS: Whether diabetes without insulin therapy is an independent cardiovascular (CV) risk factor in atrial fibrillation (AF) has recently been questioned. We investigated the prognostic relevance of diabetes with or without insulin treatment in patients in the ARISTOTLE trial. METHODS AND RESULTS: Patients with AF and increased stroke risk randomized to apixaban vs. warfarin were classified according to diabetes status: no diabetes; diabetes on no diabetes medications; diabetes on non-insulin antidiabetic drugs only; or insulin-treated. The associations between such patient subgroups and stroke/systemic embolism (SE), myocardial infarction (MI), and CV death were examined by Cox proportional hazard regression, both unadjusted and adjusted for other prognostic variables. Patients with diabetes were younger and had a higher body mass index. Median CHA2DS2VASc score was 4.0 in patients with diabetes and 3.0 in patients without diabetes. We found no significant difference in stroke/SE incidence across patient subgroups. Compared with no diabetes, only insulin-treated diabetes was significantly associated with higher risk. When adjusted for clinical variables, compared with no diabetes, the hazard ratios (HRs) for MI (95% confidence intervals) were for diabetes on no medication: 1.15 (0.62-2.14); for diabetes on non-insulin antidiabetic drugs: 1.32 (0.90-1.94); for insulin-treated diabetes: 2.34 (1.43-3.82); interaction P = 0.008. HRs for CV death were for diabetes on no medication: 1.19 (0.86-166); for diabetes on non-insulin antidiabetic drugs: 1.12 (0.88-1.42); for insulin-treated diabetes 1.85 (1.36-2.53), interaction P = 0.001. CONCLUSION: In anticoagulated patients with AF, a higher risk of MI and CV death is largely confined to diabetes treated with insulin.
AIMS: Whether diabetes without insulin therapy is an independent cardiovascular (CV) risk factor in atrial fibrillation (AF) has recently been questioned. We investigated the prognostic relevance of diabetes with or without insulin treatment in patients in the ARISTOTLE trial. METHODS AND RESULTS: Patients with AF and increased stroke risk randomized to apixaban vs. warfarin were classified according to diabetes status: no diabetes; diabetes on no diabetes medications; diabetes on non-insulin antidiabetic drugs only; or insulin-treated. The associations between such patient subgroups and stroke/systemic embolism (SE), myocardial infarction (MI), and CV death were examined by Cox proportional hazard regression, both unadjusted and adjusted for other prognostic variables. Patients with diabetes were younger and had a higher body mass index. Median CHA2DS2VASc score was 4.0 in patients with diabetes and 3.0 in patients without diabetes. We found no significant difference in stroke/SE incidence across patient subgroups. Compared with no diabetes, only insulin-treated diabetes was significantly associated with higher risk. When adjusted for clinical variables, compared with no diabetes, the hazard ratios (HRs) for MI (95% confidence intervals) were for diabetes on no medication: 1.15 (0.62-2.14); for diabetes on non-insulin antidiabetic drugs: 1.32 (0.90-1.94); for insulin-treated diabetes: 2.34 (1.43-3.82); interaction P = 0.008. HRs for CV death were for diabetes on no medication: 1.19 (0.86-166); for diabetes on non-insulin antidiabetic drugs: 1.12 (0.88-1.42); for insulin-treated diabetes 1.85 (1.36-2.53), interaction P = 0.001. CONCLUSION: In anticoagulated patients with AF, a higher risk of MI and CV death is largely confined to diabetes treated with insulin.
Authors: Giuseppe Patti; Ladislav Pecen; Giuseppina Casalnuovo; Marius Constantin Manu; Paulus Kirchhof; Raffaele De Caterina Journal: Clin Res Cardiol Date: 2022-08-17 Impact factor: 6.138