DAPT equivalent to IV Alteplase in achieving functional outcomes after Acute Ischemic Stroke
The ARAMIS Randomized Clinical Trial revealed that the dual antiplatelet therapy was as effective as intravenous alteplase in achieving better functional outcomes at 90 days in patients with minor non-disabling acute ischemic stroke who presented within 4.5 hours of symptom onset. The trial results were published in the journal JAMA Network.
Nearly half of the patients having acute ischemic stroke suffer from minor strokes. Recent guidelines recommend intravenous alteplase for patients with acute ischemic stroke (AIS) presenting within 4.5 hours of symptom onset. But there is inconclusive evidence on the use of intravenous thrombolysis for these patients. As previous literature shows that dual antiplatelet therapy is safe and efficacious in patients presenting with minor stroke within 12 and 24 hours of symptom onset, researchers conducted a study to investigate whether dual antiplatelet therapy (DAPT) is non-inferior to intravenous thrombolysis among patients with minor non-disabling acute ischemic stroke.
A multicenter, open-label, blinded endpoint, noninferiority randomized clinical trial was carried out on 760 patients with acute minor non-disabling stroke. The trial was carried out at 38 hospitals in China from October 2018 through April 2022 with a final follow-up on July 18, 2022. Randomization was done on eligible patients within 4.5 hours of symptom onset with the DAPT group having 393 patients and the alteplase group having 367. The DAPT group received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase.
The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The non-inferiority of DAPT to alteplase was defined based on a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to −4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day endpoints were assessed in a blinded manner. A safety endpoint was symptomatic intracerebral hemorrhage up to 90 days.
Key findings:
- Among 760 eligible randomized patients with a median [IQR] age of 64 [57-71] years, there were 223 [31.0%] women and a median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial.
- At 90 days, More patients in the DAPT group (93.8% of patients [346/369]) than in the alteplase group (91.4% [320/350]) had an excellent functional outcome.
- The unadjusted lower limit of the 1-sided 97.5% CI was −1.5%, which is larger than the −4.5% noninferiority margin (P for noninferiority <.001).
- About 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group had symptomatic intracerebral hemorrhage at 90 days.
Thus, DAPT was non-inferior to intravenous alteplase when administered within 4.5 hours of stroke onset for the primary outcome of excellent functional outcome at 90 days.
Further reading: Chen H, Cui Y, Zhou Z, et al. Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke: The ARAMIS Randomized Clinical Trial. JAMA. 2023;329(24):2135–2144. doi:10.1001/jama.2023.7827
