Welcome to PracticeUpdate! We hope you are enjoying access to a selection of our top-read and most recent articles. Please register today for a free account and gain full access to all of our expert-selected content.
Already Have An Account? Log in Now
Effectiveness and Safety of Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke
abstract
This abstract is available on the publisher's site.
Access this abstract nowIMPORTANCE
Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking.
OBJECTIVE
To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke.
DESIGN, SETTING, AND PARTICIPANTS
This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome.
INTERVENTIONS
Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio.
MAIN OUTCOMES AND MEASURES
The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points.
RESULTS
Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups.
CONCLUSIONS AND RELEVANCE
Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke.
Additional Info
Disclosure statements are available on the authors' profiles:
Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial
JAMA Neurol 2024 Mar 11;[EPub Ahead of Print], HS Chen, Y Cui, XH Wang, YT Ma, J Han, YJ Duan, J Lu, LY Shen, Y Liang, WZ Wang, H Wang, Y Zhao, JT Zhang, YL Song, XM He, RH Li, DB Tao, J Li, SM Huang, N Wang, M Hong, C Meng, W Zhang, DL Wang, TN NguyenFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The CHANCE1 and POINT2 trials demonstrated the efficacy of dual antiplatelet therapy with clopidogrel–aspirin in patients with transient ischemic attack or minor ischemic stroke when initiated within 12 to 24 hours. The INSPIRES trial extended these findings to patients with an NIHSS score of 4 to 5 at up to 72 hours after onset, showing that clopidogrel added to aspirin reduces recurrent stroke risk in patients with atherosclerotic minor stroke and high-risk TIA.3 The POINT and INSPIRES trials found modestly increased bleeding risks that extended over a period of 90 days.2,3 Secondary analyses have suggested that the benefits of additional antiplatelet therapies occur early, within 21 days.4,5
In comparison, the ATAMIS trial enrolled a broader population of 3000 patients with mild to moderate deficits (NIHSS score, 4–10) at up to 48 hours after onset and used early neurologic deterioration (END) at 7 days as the primary outcome. END, defined as an NIHSS score worsening of 2 or more points, captures both recurrent strokes and infarct progression, which are difficult to distinguish clinically. Notably, the benefit of clopidogrel added to aspirin accrued within the first 7 days (4.8% vs 6.7%, respectively), confirming a very early treatment effect. The ATAMIS trial also used a shorter 14-day course of clopidogrel–aspirin compared with prior trials.1,2 With this abbreviated duration, a significant reduction of END rates was observed, without an excess risk of bleeding events with added clopidogrel (0.7% vs 1.0%, respectively). This suggests that even abbreviated treatment with clopidogrel–aspirin may confer benefit, if initiated promptly after symptom onset.
The ATAMIS trial provides important insights, supporting brief treatment with clopidogrel–aspirin in patients with moderate stroke and after 24 hours. Questions remain regarding whether treatment can be based primarily on stroke mechanism (suspected atheroembolism) rather than strict NIHSS score cutoffs and whether ticagrelor–aspirin may be superior to clopidogrel–aspirin in certain patients.
References