Hyperglycemia And Hypertension Predict Subsequent Ischemic Stroke In Patients With Minor Stroke Or TIA Treated With Dual Antiplatelet Therapy: A Post-hoc Analysis Of The POINT Trial

Background: Randomized trials have shown that dual antiplatelet therapy (DAPT) reduces the risk of subsequent ischemic stroke in patients with minor stroke or high-risk TIA (MS-TIA). However, the 90 day risk remains elevated at 5-8%. In this exploratory study, we aimed to identify predictors of subsequent ischemic stroke in patients with MS-TIA treated with DAPT. Methods: This is a post-hoc analysis of the POINT trial that randomized patients with MS-TIA to DAPT versus aspirin monotherapy. For this analysis, we included only patients treated with DAPT and performed univariate and adjusted Cox-regression analyses to determine predictors of subsequent ischemic stroke. We also performed receiver operating analysis to determine predictive accuracy. P<0.05 was considered statistically significant. Results: Among 2,398 MS-TIA patients treated with DAPT, 109 (4.5%) had ischemic stroke during the 90 day follow up interval. In Cox-regression analyses, predictors of subsequent ischemic stroke were admission glucose level per 10 mg/dL increase (adjusted HR 1.04 95% CI 1.03-1.06, p < 0.001), admission blood pressure per 10 mm Hg increase (aHR 1.10 95% CI 1.03-1.17, p = 0.006) and presence of infarct on index imaging (adjusted HR 2.04 95% CI 1.40-2.98, p<0.001). Subsequent stroke risk was particularly increased in patients with serum glucose ≥180 mg/dL (adjusted HR 2.45 95% CI 1.60-3.75, p<0.001) and systolic blood pressure ≥180 mmHg (adjusted HR 1.71 95% CI 1.16-2.52, p = 0.007). The rate of subsequent stroke when both predictors were present was 14.7% and when none was present was 3.3%. Their independent predictive accuracy was modest in receiver operating curves: glucose (AUC = 0.66 95% CI 0.61-0.71) and systolic blood pressure (AUC = 0.60 95% CI 0.54-0.65). Findings were similar in a sensitivity analysis where patients without imaging confirmation of subsequent stroke were excluded. Conclusion: Patients with MS-TIA who have hyperglycemia or hypertension on admission are at a relatively high risk of subsequent ischemic stroke despite DAPT. Future studies are needed to validate our findings and explore whether targeted treatment of these factors can affect short term stroke risk.