Impact of Anticoagulants, Antiplatelet Agents, and Oral Antidiabetic Drugs on the Risk of Stroke in Patients with Diabetes and Nonvalvular Atrial Fibrillation: A Case-Referent Study

Background Type 2 diabetes mellitus (T2DM) and atrial fibrillation are risk factors for stroke. The potential preventive effects of cardiovascular and antidiabetic treatments on stroke risk in patients with these diseases remain insufficiently documented. Sulfonylureas have also been reported to be associated with stroke. This study aimed to assess the risk of stroke according to the use of drugs (anticoagulants, antiplatelet agents, and oral antidiabetic drugs [OADs]) in patients with T2DM and nonvalvular atrial fibrillation (NVAF). Methods Patients with a history of T2DM and NVAF were identified from two systematic registries: a registry of patients with stroke and a registry of patients with atrial fibrillation. Patients with stroke were randomly matched to patients without prior stroke events based on age, sex, body mass index, and index date. All treatments administered 12 months before the index date were documented. The associations between anticoagulants, antiplatelet agents, and OADs and stroke were assessed using multivariate conditional logistic models that yielded adjusted odds ratios (aORs) and 95% confidence intervals, controlling for risk factors identified in the univariate comparison of cases and matched referents. Results Three-hundred and fifteen patients with stroke with both diabetes and NVAF were matched to 523 referents with both diabetes and NVAF but no history of stroke. The aORs for the use of drugs and stroke were 0.24 [0.15-0.40] for direct oral anticoagulants (DOACs), 0.42 [0.27-0.67] for vitamin K agonists (VKA), 0.80 [0.52-1.24] for antiplatelet agents, and 0.68 [0.45-1.02] for OADs. No significant associations were found between individual OAD use and stroke risk. Similar results were obtained for ischemic stroke. Only VKAs were significantly associated with hemorrhagic stroke (odds ratio=4.25 [1.16-15.64]). Conclusions Anticoagulant use was associated with a protective effect against the risk of stroke in patients with diabetes and NVAF, with no increase in the risk of hemorrhagic stroke for DOAC. No increased risk of stroke was observed because of any OAD, including sulfonylureas.