DALLAS — Dual antiplatelet therapy (DAPT) proved non-inferior to IV alteplase in Chinese patients with minor non-disabling stroke, a researcher reported.
In the ARAMIS trial of patients with acute minor stroke who presented within 4.5 hours of onset, and had no “clearly disabling deficit,” functional outcome was similar between the two methods, according to Thanh N. Nguyen, MD, of Boston University Chobanian & Avedisian School of Medicine, in a presentation at the American Stroke Association International Stroke Conference (ISC).
The trial’s primary outcome of a Modified Rankin Scale 0-1 at 90 days was achieved by 93.8% of patients in the DAPT arm and 91.4% in the IV alteplase arm.
“In the modified ITT [intention to treat] population, the risk difference of having an excellent outcome at 90 days was 2.3% (95% CI -1.5% to -6.1%),” according to ARAMIS investigators, including Hui-Sheng Chen, MD, of General Hospital of Northern Theater Command in Shenyang, China. Nguyen presented the results at ISC on their behalf.
Previous research has supported DAPT in patients with minor stroke (NIH Stroke Scale/Score or NIHSS ≤5), Nguyen noted. “You are familiar with the POINT and CHANCE trials, which confirmed the efficacy and safety of DAPT in patients presenting with minor stroke within 12 or 24 hours, respectively. Moreover, CHANCE found that the benefit of reducing recurrent stroke was more effective in the first 2 weeks.”
She also cited the PRISMS trial, which turned in a less-positive result for alteplase versus aspirin for favorable functional outcome at 90 days, although the study was terminated early because of low patient recruitment.
In a 2018 JAMA editorial, William J Powers, MD, of the University of North Carolina at Chapel Hill, pointed out that “[e]xperience with intravenous alteplase in acute ischemic stroke has defined many clinical situations in which the overall benefit of reducing disability with treatment outweighs the risk of hemorrhage.”
“However, situations remain for which data are insufficient,” he stated. “Current guidelines from the American Heart Association/American Stroke Association (AHA/ASA) recommend intravenous alteplase administration within 3 hours for patients with mild but disabling stroke symptoms but are indecisive about those with nondisabling symptoms. It is this latter group of patients that has posed a persistent therapeutic dilemma: treat because they might get worse or do not treat because of the risk of symptomatic intracranial hemorrhage?”
Nguyen stated that those 2018 AHA/ASA guidelines green lit IV alteplase as an option within 3 hours of onset for patients with mild ischemic stroke, and that the Chinese Stroke Association Guidelines recommended the same.
In ARAMIS, DAPT consisted of 300-mg clopidogrel and 100-mg aspirin on day 1 of treatment, then 75-mg clopidogrel with 100-mg aspirin for 10-14 days. IV alteplase consisted of 0.9 mg/kg on day 1 and then guideline-based treatment for the next 2 weeks.
ARAMIS patients in both arms had a median age around 64 and the majority were male, while about a third were current smokers. The median NIHSS was 2. The time from symptom onset to treatment was about 180 minutes. The researchers noted that the trial’s crossover rate of 20.4% “may have affected the integrity of the recruitment and consent process.”
Nguyen reported that fewer patients in the DAPT arm versus IV alteplase experienced early neurologic deterioration within 24 hours (4.6% vs 9.1%). In terms of safety, any bleeding event occurred in 1.6% of the DAPT arm versus 5.4% of the IV alteplase arm, for a -3.6% risk difference (P=0.01).
Those in the DAPT arm versus IV alteplase arm saw lower risk for symptomatic intracranial hemorrhage (ICH) at 0.3% versus 0.9%, although the risk difference (-2.4%) was not statistically significant (P=0.63). Symptomatic ICH was defined as bleeding on CT with neurological deterioration (NIHSS ≥4-point increase).
During ARAMIS, the 2019 AHA/ASA guidelines included DAPT as a standard treatment within 3-4.5 hours following symptom onset. For IV alteplase treatment, the updated guidelines stated that “for eligible patients with mild nondisabling stroke symptoms (NIHSS score 0-5), IV alteplase is not recommended for patients who could be treated within three hours of ischemic stroke symptom onset or patient last known well or at baseline state.”
While the change in the guidelines was listed as a limitation of ARAMIS, it boosts the trial’s findings, according to Nguyen. “So in the middle of the trial, the guidelines had been updated to consider dual antiplatelet as a standard treatment,” she said. “Given the ease of administration, the less intensive monitoring, the low cost and safety profile of dual antiplatelet therapy, the current findings support the use of dual antiplatelet in this population.”
ARAMIS was funded by the National Key R&D Program of China and the Science and Technology Project Plan of Liaoning Province. Aspirin and clopidogrel were donated by Shenzhen Salubris Pharmaceutical.
Nguyen disclosed relationships with Medtronic and the Society of Vascular and Interventional Neurology.
International Stroke Conference
Source Reference: Chen H-S, et al “Antiplatelet versus alteplase in acute mild ischaemic stroke (Aramis): a multicentre, open-label, blinded- endpoint, randomised, controlled, noninferiority trial” ISC 2023.