ARAMIS boosts DAPT potential for mild stroke

In the ARAMIS* trial, dual antiplatelet therapy (DAPT) using clopidogrel and aspirin was noninferior to intravenous thrombolysis (IVT) using alteplase in Chinese patients with minor nondisabling ischaemic stroke presenting within 4.5 hours of symptom onset.

About 94 percent of participants on DAPT achieved the primary endpoint of excellent functional outcome of modified Rankin score 0–1 at 90 days. With alteplase, 91.4 percent achieved excellent outcomes. [ISC 2023, abstract LB23]

“In the modified intention-to-treat (ITT) population, the risk difference of having an excellent outcome at 90 days was 2.3 percent,” said Dr Thanh Nguyen from Boston Medical Center, Boston, Massachusetts, US, who presented the findings at ISC 2023.

“The unadjusted lower limit of the one-sided 97.5 percent confidence interval was –1.5 percent,” noted Nguyen, which was greater than the –4.5 percent boundary of the noninferiority margin (p_{noninferiority}=0.0002). “Therefore, this was a positive trial,” she said.

ARAMIS comprised 760 participants (median age 64 years, 69 percent male) from 38 hospitals in China to evaluate the effect of DAPT in acute minor stroke patients without clearly disabling deficits (median NIHSS** 2) and compared it against IV alteplase.

Nguyen, presenting on behalf of study investigator Professor Hui-Sheng Chen from the General Hospital of Northern Theater Command, Shenyang, Liaoning, China, noted that patients should have no score in the consciousness item at the time of randomization. “[If patients] had lethargy, [they] were not allowed to be included in the trial because we did not want to confound with potential stroke mimics [in patients] who had potential metabolic encephalopathy.”

Participants were randomized in a 1:1 ratio. Those on DAPT received a 300-mg loading dose of clopidogrel and aspirin 100 mg on day 1, followed by 10–14 days of clopidogrel 75 mg and aspirin 100 mg. Guideline-based antiplatelet therapy was given thereafter up to day 90. In the IVT arm, participants received IV alteplase at the standard dose of 0.9 mg/kg (90 mg max), followed by guideline-based antiplatelet treatment. Crossover rates were between 16 and 20 percent. Median time from symptom onset to treatment was 3 hours.

Secondary, safety outcomes

Early neurologic deterioration within 24 hours was twice as frequent with IVT vs DAPT (9.1 percent vs 4.6 percent), but the rates of other secondary outcomes were similar between arms.

In terms of any bleeding event, the rate was significantly lower with DAPT vs IVT (1.6 percent vs 5.4 percent; p=0.01).

Only one patient on DAPT (0.3 percent) had a symptomatic intracranial haemorrhage, as opposed to three in the IVT arm (0.9 percent). The risk difference was not significant (p=0.63).

“Across predefined subgroups, the only signal that might stand out is that the point estimates seemed better in [alteplase-treated] patients who had higher NIHSS. Otherwise, the other subgroups look largely similar,” said Nguyen.

Robust evidence

The current findings build on previous evidence substantiating the efficacy and safety of DAPT in patients with acute ischaemic stroke and transient ischaemic attack. [N Engl J Med 2013;369:11-19; N Engl J Med 2018;379:215-225] “However, the crossover rate may have affected the integrity of the recruitment and consent processes,” Nguyen pointed out.

“Nonetheless, the demonstration of the noninferiority of DAPT to IV alteplase was robust given the concordance of our findings by the modified ITT, per-protocol, and as-treated analyses,” Nguyen said. “Given the ease of administration, less intensive monitoring low cost, and safety profile of DAPT, the current findings support [its use] in this population.”