Risk factors associated with 90-day recurrent stroke in patients on dual antiplatelet therapy for minor stroke or high-risk TIA: a subgroup analysis of the CHANCE trial

Abstract

ObjectiveMany patients receiving dual antiplatelet therapy still had recurrent strokes. We aimed to identify factors associated with recurrent stroke at 90 days in patients receiving dual antiplatelet therapy in Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events trial.MethodsPatients with transient ischaemic attack or minor stroke receiving clopidogrel and aspirin in the trial were analysed in the study. The primary outcome was recurrent stroke within 90 days after the index event. Cox proportional hazard model with backward selection was used to identify factors associated with stroke.ResultsAmong 2584 patients, 212 (8.2%) had a recurrent stroke, 216 (8.4%) had a composite of stroke, myocardial infarction, or vascular death and 204 (7.9%) had ischaemic stroke within 90 days. Multivariate analysis identified the following factors associated with stroke: history of hypertension with poor blood pressure control (HR, 1.92; 95% CI 1.22 to 3.03), the high baseline National Institute of Health Stroke Scale (NIHSS) score of 2 and 3 (2.12 (1.07 to 4.21) and 4.11 (2.05 to 8.22), respectively), time from onset to randomisation of <12 hours (1.47 (1.12 to 1.94)), the lipid-lowering therapy (0.61 (0.47 to 0.83)), the open-label aspirin dose at day 1 of ≥300 mg (1.98 (1.45 to 2.69)). Intracranial arterial stenosis (ICAS) was significantly associated with stroke in the sensitivity analysis (2.17 (1.16 to 4.04)).ConclusionsThe high baseline NIHSS score, hypertension with poor blood pressure control, ICAS, time from onset to randomisation of less than 12 hours and no lipid-lowering therapy were associated with stroke, suggesting that patients with identified predictors still remain to be at high risk of recurrent stroke although being under the dual antiplatelet therapy.Trial registration numberhttp://clinicaltrials.gov/show/NCT00979589. ClinicalTrials.gov number: NCT00979589

Reevaluation of risk factors for time to subsequent events after first stroke occurrence using a new weighted all-cause effect measure

“…The mortality in the study group is low due to the selection of "cases" within the underlying case-control study, in which strokes with severe impairment were excluded. However, similar stroke rates were found in other studies [3,8,26]. The low event number also results in a limited accuracy of the estimates as expressed by wide confidence intervals.…”

“…Serving as a model for this biometrical approach the present study clearly shows that the associations of well-known risk factors and risk diseases for the occurrence of a first stroke do not apply anymore during the period of secondary prevention. By this new methodologic approach our study differs from other studies, which exclusively examined either the risk for a recurrent stroke or the risk for death [7][8][9]. However, choosing the appropriate weights remains to be challenging and should be further discussed in detail by medical and statistical experts.…”

“…Commonly known risk factors and risk diseases for a first ever stroke like atrial fibrillation, hypertension, diabetes mellitus, smoking, or high cholesterol are well accepted of being responsible for about 50-70 percent of all strokes [5,6]. Risk factors for subsequent strokes after a first non-fatal stroke event were also analyzed but more heterogeneous results were gained with indicators including diabetes mellitus, coronary artery disease, hypertension, a high baseline score on the "National Institute of Health Stroke Scale", intracranial arterial stenosis, or hyperlipidemia [7][8][9]. Although a recent meta-analysis suggested that hypertension, diabetes mellitus, atrial fibrillation, and coronary heart disease might be risk factors for a subsequent stroke occurrence, they did not consider a time-to-event analysis [10].…”

Reevaluation of risk factors for time to subsequent events after first stroke occurrence using a new weighted all-cause effect measure

“…The mortality in the study group is low due to the case selection for the underlying case-control study, in which strokes with severe impairment were excluded. However, similar stroke rates were found in other studies [3,8,25]. The low event number also results in a limited accuracy of the estimates as expressed by wide confidence intervals.…”

“…Common known risk factors for first ever stroke like atrial fibrillation, hypertension, diabetes mellitus, smoking, or high cholesterol are well accepted and explain about 50-70 percent of all strokes [5,6]. For subsequent strokes after a first non-fatal stroke event, risk factors were also analyzed but more heterogeneous results were gained with indicators including diabetes mellitus, coronary artery disease, hypertension, a high baseline score on the National Institute of Health Stroke Scale, intracranial arterial stenosis, or hyperlipidemia [7][8][9].…”