DAPT Noninferior to IV Alteplase for Minor Nondisabling Acute Ischemic Stroke

Dual antiplatelet therapy (DAPT) within 4.5 hours of symptom onset is noninferior to intravenous alteplase for excellent functional outcome at 90 days in patients with minor nondisabling acute ischemic stroke, according to a study in JAMA.

The randomized, open-label, noninferiority ARAMIS (Antiplatelet vs R-tPA for Acute Mild Ischemic Stroke; ClinicalTrials.gov Identifier: NCT03661411) trial evaluated the efficacy and safety of DAPT in 38 hospitals in China.

Eligible participants were aged 18 years or older and had an acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less, with 1 or fewer points on single-item scores, and could begin to receive study treatment within 4.5 hours of stroke symptoms.

The patients were randomly assigned in a 1:1 ratio to receive DAPT or intravenous alteplase. The alteplase group received 0.9 mg/kg (10% as a bolus, 90% infused for 1 hour) to a maximum of 90 mg, followed by guideline-based antiplatelet treatment beginning 24 hours after intravenous thrombolysis. The DAPT group received a loading dose of 300 mg of clopidogrel on the first day, followed by 75 mg per day for 12 (±2) days; 100 mg of aspirin on the first day, followed by 100 mg daily for 12 (±2) days; and single antiplatelet therapy or DAPT based on guidelines until 90 days.

The primary outcome was excellent functional outcome at 90 days, which was a modified Rankin Scale (mRS) score of 0 to 1. The noninferiority margin of -4.5% was based on the Third International Stroke Trial.

The full analysis set included 719 patients (369 in the DAPT group [median age, 65 years; 69.5% men] and 350 in the alteplase group [median age, 64 years; 68.6% men]) who were enrolled from October 1, 2018, to April 18, 2022. Participants’ median NIHSS score was 2 (IQR, 1-3). The DAPT group had a median time from stroke onset to treatment of 182 (IQR, 133- 230) minutes vs 180 (IQR, 126-225) minutes in the alteplase group.

Regarding the primary outcome, the percentage of patients who had mRS scores of 0 or 1 at 90 days was 93.8% in the DAPT group and 91.4% in the alteplase group. The risk difference of an excellent outcome at 90 days was 2.3% (unadjusted 95% CI, -1.5% to 6.2%; P <.001 for noninferiority; adjusted 95% CI, -1.6% to 6.1%) in the full analysis set. Similar findings were observed in the per-protocol and as-treated analyses.

DAPT was noninferior to intravenous alteplase because the lower boundary of the 2-sided 95% (1-sided 97.5%) CI was greater than the prespecified value of -4.5%.

Patients in the DAPT group had early neurologic deterioration at 24 hours vs the alteplase group in the full analysis set (unadjusted risk difference, -4.5% [95% CI, -8.2% to -0.8%]; adjusted risk difference, -4.6% [95% CI, -8.3% to -0.9%]).

In the DAPT group, 1 patient had symptomatic intracerebral hemorrhage (sICH) and 6 patients had other bleeding events. In the alteplase group, 3 patients had sICH and 19 patients had other bleeding events.

Limitations include the noninferiority, open-label design and high crossover rate (20.4%). Also, patients with possible cardioembolism were excluded, and fewer women than men were enrolled. Furthermore, high rates of the primary endpoint in the DAPT and alteplase groups may have had a ceiling effect that limited the opportunity for either agent to show superiority to the other.

“Among patients presenting with minor nondisabling acute ischemic stroke within 4.5 hours of symptom onset, dual antiplatelet treatment was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days,” the study authors wrote.

Disclosure: The antiplatelet medications including aspirin and clopidogrel were donated by Shenzhen Salubris Pharmaceutical Co, Ltd. One of the study authors declared an affiliation with a biotech company. Please see the original reference for a full list of authors’ disclosures.