medwireNews: Treating patients with acute mild-to-moderate stroke with aspirin plus clopidogrel reduces the risk for early neurological deterioration at 7 days compared with aspirin alone, suggests the ATAMIS study published in JAMA Neurology.
“For patients with mild to moderate ischemic stroke, aspirin monotherapy is recommended by stroke guidelines; however, early neurologic deterioration remains a challenge to overcome in this population, given the association of early neurologic deterioration with clinical outcome,” explain Hui-Sheng Chen (General Hospital of Northern Theater Command, Shenyang, China) and colleagues.
To investigate whether dual antiplatelet therapy (DAPT) may help, they enrolled 3000 patients (median age 65.9 years; 64.6% men) from 66 centers in China who had presented with stroke symptoms within the last 48 hours and had a National Institutes of Health Stroke Scale (NIHSS) score of between 4 and 10 points (median 5 points), indicating mild-to-moderate ischemic stroke.
Eligible patients were functioning independently prior to the event, with a modified Rankin Scale (mRS) score of up to 1 point, where 0 indicates no symptoms. All the patients were ineligible for intravenous thrombolysis or endovascular therapy.
Chen and colleagues randomly assigned patients to receive daily aspirin 100 mg plus clopidogrel (300 mg loading dose followed by 75 mg/day from day 2 to 14 and aspirin or clopidogrel from day 15 to 90), or aspirin alone (100–300 mg/day from day 1 to 14 and 100 mg/day from day 15 to 90).
At day 7, the proportion of patients who had neurological deterioration, defined as an increase of at least 2 points on the NIHSS, was significantly lower among the 1502 patients receiving DAPT than among the 1413 receiving aspirin alone, at 4.8% versus 6.7%.
This translated to a significant difference of 1.9 percentage points between the two treatments in favor of DAPT, after adjustment for prognostic factors such as age, sex, NIHSS score, stroke etiology, and history of diabetes and hypertension. And the difference fell only marginally to 1.8 percentage points in the per-protocol analysis.
There were no differences between the two treatment arms for the secondary endpoints of new ischemic or hemorrhagic stroke at 90 days, mRS score improvement at 90 days, change in NIHSS score, or other vascular or death events occurring within 90 days.
The researchers suggest that the lack of superior improvement in the 90-day functional outcomes with DAPT over aspirin alone may be due to “the relatively mild neurological deficits in the enrolled patients.”
The DAPT and aspirin groups had similar rates of adverse events, at a respective 8.7% and 9.6%, which included mucocutaneous hemorrhage (0.2 vs 0.1%), organ hemorrhage (0.3 vs 0.3%), intracranial hemorrhage (0.1 vs 0.1%), and bleeding rate (0.7 vs 1.0%).
Chen et al comment that this low rate may have been due to the shorter 10–14-day dosing duration of DAPT in the study, compared with 21 days and 90 days in the CHANCE and POINT studies, respectively.
The results also suggest the potential benefit of earlier intervention with intensive antiplatelet therapy, given that the majority (60%) of patients in the study were treated within 24 hours of their stroke, say the investigators.
They acknowledge that the generalizability of ATAMIS might be limited by the exclusion of patients eligible for thrombolysis and endovascular treatment, and that a 2-point reduction in NIHSS at 7 days “may not have been an optimal definition of early neurologic deterioration.”
Nevertheless, the team concludes that “dual antiplatelet therapy, compared with aspirin alone, may be a superior treatment option in patients with acute mild to moderate ischemic stroke,” and call for further clinical trials particularly in those presenting within 24 hours of symptom onset.
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