DAPT Maintains Early Neurologic Function in Mild-Moderate Stroke

In certain patients with mild-to-moderate acute ischemic stroke, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel (Plavix) reduced early neurologic deterioration better than aspirin alone, the Chinese randomized multicenter ATAMIS trial found.

Early neurologic deterioration — as measured by an increase of 2 or more points on the National Institutes of Health Stroke Scale (NIHSS) at 7 days — occurred in fewer of those on DAPT (4.8% vs 6.7%, P=0.03), reported Hui-Sheng Chen, MD, of the General Hospital of Northern Theater Command in Shenyang, China, and colleagues in JAMA Neurology.

Yet there were no differences in secondary endpoints including excellent functional outcome at 90 days, defined as a modified Rankin (mRS) score of 0-1; occurrence of new ischemic or hemorrhagic stroke within 90 days; change in NIHSS score at 14 days; or occurrence of other vascular events or death within 90 days.

Patients in the study were not eligible for intravenous thrombolysis or endovascular therapy, and DAPT or aspirin therapy was initiated within 48 hours of symptom onset.

“Treatment with clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with comparable safety profile,” Chen and colleagues concluded.

“Given a lack of improvement of 90-day clinical outcome and the benefit of earlier dual antiplatelet treatment observed in this study,” they noted, “future clinical trials focusing on patients with mild-to-moderate stroke presenting within 24 hours of symptom onset are needed.”

Current stroke guidelines recommend aspirin monotherapy for patients with mild-to-moderate ischemic stroke. Early neurologic deterioration remains a challenge to overcome in this population, however, and is associated with clinical outcome.

ATAMIS was the first large-scale DAPT trial that enrolled patients with NIHSS scores of 4-10 who were not eligible for intravenous thrombolysis or endovascular therapy.

Notably, investigators tested a brief 10-14 day course of DAPT in order to avoid excess bleeding in patients. Indeed, safety was comparable between the two groups, with a bleeding event rate of 0.7% for the DAPT group and 1% for controls in this study. Nor were there any differences in other adverse events.

Prior work showed that clopidogrel-aspirin treatment quickly turned a benefit of reduced major ischemic events compared with aspirin alone for people with high-risk transient ischemic attack (TIA) or minor ischemic stroke (NIHSS score 3 or less), based on a pooling of the CHANCE and POINT trials.

Last year, the ARAMIS trial had shown that DAPT was noninferior to IV alteplase for people with minor nondisabling strokes, the median NIHSS score being 2 for this group.

For the ATAMIS study, 3,000 patients from 66 Chinese sites were randomized from 2016 to 2022 to either clopidogrel plus aspirin (n=1,541) or aspirin alone (n=1,459).

Patients were included if they were adults with acute ischemic stroke at the time of randomization, had been functioning independently before the stroke, and were enrolled within 48 hours of stroke symptom onset. Patients who met eligibility criteria for thrombolysis or endovascular therapy were given this treatment and excluded from the study. Others with a clear indication for anticoagulation or a history of intracerebral hemorrhage, among other criteria, were excluded.

The clopidogrel group got a loading dose of 300 mg plus 100 mg aspirin, then 75 mg of clopidogrel and 100 mg of aspirin per day from day 2-14, followed by the same doses of clopidogrel or aspirin for days 15-90. The control group was given 100-300 mg aspirin until day 14, followed by 100 mg aspirin per day until day 90.

Crossovers, poor compliance, and other exclusion criteria shrank the randomized trial cohort to a modified intention-to-treat population of 1,502 in the DAPT arm and 1,413 in aspirin monotherapy.

The two treatment groups had well balanced baseline characteristics in both the modified intention-to-treat and per-protocol analyses. Study participants were 64.6% men, with a mean age of 65.9 years, and a mean NIHSS score of 5 at admission.

Chen’s group acknowledged that study limitations included an imbalance in sample size between groups, open-label design, and a large proportion of patients with mild neurologic deficit enrolled in the trial. The results cannot be generalized to patients receiving thrombolysis and endovascular treatment, who were excluded, and need to be confirmed in other populations.

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