Heterogeneity of diabetes as a risk factor for major adverse cardiovascular events in anticoagulated patients with atrial fibrillation: an analysis of the ARISTOTLE trial

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.

Prognostic significance of diabetes mellitus in patients with atrial fibrillation

“…Additionally, DM patients under both insulin and oral medication had worse prognosis than those solely on diet or lifestyle measures, which is logically paralleled to the severity of DM encountered in the respective groups and confounding comorbidities. This finding accords with recent studies showing that patients under insulin-treatment were more likely to suffer thromboembolic events [21][22][23]. However, the present analysis showed that a higher risk for death or stroke is not confined only to insulin-treated diabetic patients, but concerns the entire diabetic population, regardless of their treatment.…”

Prognostic significance of diabetes mellitus in patients with atrial fibrillation

“…Additionally, DM patients under both insulin and oral medication had worse prognosis than those solely on diet or lifestyle measures, which is logically paralleled to the severity of DM encountered in the respective groups and confounding comorbidities. This nding accords with recent studies showing that patients under insulin-treatment were more likely to suffer thromboembolic events [21][22][23] . However, he present analysis showed that a higher risk for death or stroke is not con ned only to insulin-treated diabetic patients, but concerns the entire diabetic population, regardless of their treatment.…”

Oral anticoagulation across diabetic subtypes in patients with newly diagnosed atrial fibrillation: A report from the GARFIELD‐AF registry

“…The risk of clinical outcomes, particularly, death and non‐haemorrhagic stroke incurred by diabetes in AF remains controversial. Some reported that insulin‐only treated DM was associated with a higher risk of stroke 9 or of non‐haemorrhagic stroke and CV death 10,44 ; whereas others reported a similar risk of non‐haemorrhagic stroke/SE in both OAD and insulin‐treated patients 8 . Other reports showed no excess of non‐haemorrhagic stroke/SE compared with patients without DM, but a higher risk of death 25,28 .…”

“…6 Insulin-requiring DM (IRD) and non-insulin-requiring DM (NIRD) may have a different impact on outcomes. [8][9][10] Further, DM is associated with a high prevalence and incidence of AF through mechanisms common to both forms of diabetes: structural, electromechanical and autonomic atrial remodelling, as well as oxidative stress and inflammation. [11][12][13] DM is also an independent predictor of non-haemorrhagic stroke/SE in patients with AF.…”