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Bleeding Risk of Dual Antiplatelet Therapy after Minor Stroke or Transient Ischemic Attack
Anxin Wang1,2, Xia Meng1,2, Xue Tian1,2,3,4
1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Insights
Dual antiplatelet therapy after minor stroke increases bleeding risk, especially with ticagrelor-aspirin, in younger, non-diabetic, and non-smoking patients. Most bleeding events were mild and occurred early.
Area of Science:
- Neurology
- Pharmacogenomics
- Clinical Medicine
Background:
- Dual antiplatelet therapy (DAPT) is crucial after minor stroke or transient ischemic attack (TIA).
- CYP2C19 loss-of-function alleles can affect antiplatelet drug efficacy and safety.
- Understanding bleeding risk in specific patient subgroups is essential for optimizing treatment.
Purpose of the Study:
- To determine the 90-day risk of bleeding events in patients with CYP2C19 loss-of-function alleles receiving DAPT after minor stroke or TIA.
- To identify potential risk factors associated with these bleeding events.
Main Methods:
- Analysis of 6,412 patients from the CHANCE-2 trial.
- Assessed bleeding events within 90 days using GUSTO criteria.
- Multivariate analysis to identify risk factors, including drug treatment, smoking, age, and diabetes status.
Main Results:
- 250 bleeding events (3.9%) occurred within 90 days, primarily within 21 days of DAPT.
- Ticagrelor-aspirin was associated with increased bleeding compared to clopidogrel-aspirin (HR=2.21).
- Non-smoking status was linked to lower bleeding risk (HR=0.70). Increased bleeding with ticagrelor-aspirin was noted in patients <65 years and those without diabetes.
Conclusions:
- Bleeding events after DAPT for minor stroke/TIA are common early and generally mild.
- Treatment with ticagrelor-aspirin, younger age, and absence of diabetes are associated with higher bleeding risk.
- Non-smoking may be protective against bleeding in this patient population.
Objective:
This study was undertaken to identify the risk of bleeding events and potential risk factors within 90 days in patients who carried CYP2C19 loss-of-function alleles and received dual antiplatelet therapy after minor stroke or transient ischemic attack.
Methods:
A total of 6,412 patients were enrolled from the CHANCE-2 (Clopidogrel with Aspirin in High-Risk Patients with Acute Non-disabling Cerebrovascular Events II) trial. The main outcome was any bleeding within 90 days defined by the criteria from GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries).
Results:
A total of 250 (3.9%) bleeding events were reported, which occurred mainly within the 21 days of dual antiplatelet therapy (200 cases, 3.1%). Minor bleeding of the skin bruises, epistaxis, and gum bleeding were most frequent. Multivariate analysis showed that treatment with ticagrelor-aspirin compared with clopidogrel-aspirin was associated with increased bleeding (hazard ratio [HR] = 2.21, 95% confidence interval [CI] = 1.68-2.89, p < 0.001). Current smoking was associated with a lower risk of bleeding (HR = 0.70, 95% CI = 0.52-0.95, p = 0.02). Additionally, ticagrelor-aspirin compared with clopidogrel-aspirin was associated with higher risk of bleeding in patients aged <65 years (HR = 2.87, 95% CI = 1.95-4.22) and those without diabetes mellitus (HR = 2.65, 95% CI = 1.88-3.73; p for interaction = 0.04 and 0.03, respectively).
Interpretation:
Bleeding events mostly occurred within the 21-day dual antiplatelet therapy stage and were generally mild. The risk of bleeding was greater in nonsmoking patients, and was associated with treatment with ticagrelor-aspirin compared with clopidogrel-aspirin, particularly in patients aged <65 years and nondiabetic patients. ANN NEUROL 2022;91:380-388.
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