Delayed dual antiplatelet therapy significantly reduces new stroke occurrence at 90 days

Key takeaways:

• The efficacy of dual antiplatelet therapy vs. aspirin in patients with stroke was similar when given less than 24 hours to 72 hours of symptom onset.
• The risk for moderate to severe bleeding was also similar.

Initiating dual antiplatelet therapy within 72 hours of symptom onset in patients with ischemic stroke or transient ischemic attack led to a significant reduction in new stroke occurrence at 90 days, according to results of a subgroup analysis.

“Acute mild ischemic stroke or transient ischemic attack is associated with a high risk of subsequent stroke within 90 days,” Yuetong Liu, BS, from the department of neurology at Tiantan Hospital, Capital Medical University in Beijing, and colleagues wrote. “Currently, dual antiplatelet therapy is considered to be a key strategy to prevent early new stroke for these patients.”

Prior research has established that dual antiplatelet therapy (DAPT) may reduce new stroke risk in those with mild ischemic stroke or transient ischemic attack (TIA) when given within 24 hours, but it was uncertain whether a delayed treatment window impacted the risk, Liu and colleagues wrote. So, they examined the safety and efficacy of DAPT with clopidogrel and aspirin in this population when initiated within 24 hours, between 24 and 48 hours, as well as from 48 to 72 hours.

The Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis clinical trial was a randomized, double-blind, placebo-controlled, multicenter study conducted at more than 200 Chinese hospitals between September 2018 and October 2022.

A total of 6,100 individuals (median age, 65 years; 64.2% men) were randomly assigned to receive either clopidogrel combined with aspirin (clopidogrel 300 mg loading dose on day 1, followed by 75 mg daily on days 2 to 90; aspirin 100 mg to 300 mg on the first day and then 100 mg daily for days 2 to 90) or aspirin alone (100 mg to 300 mg on day 1 and then 100 mg daily for days 2 to 90) within 72 hours after symptom onset. All enrollees were split into three cohorts by time from symptom onset to randomization, with a subsequent 90-day follow up.

The primary efficacy outcome was incidence of either new ischemic or hemorrhagic stroke within that 90-day window, and the primary safety outcome was incidence of moderate to severe bleeding.

Data showed that stroke occurred within 90 days in 12.4% of patients in the 24 hours or fewer group; 8.3% in the 24 to 48 hours group; and 7% in the 48 to 72 hours group.

Those in the DAPT group registered a lower risk for new stroke within 90 days compared with the aspirin alone group across all three cohorts: 5.8% vs. 8.2% (HR = 0.7; 95% CI, 0.53-0.94) for 48 to 72 hours; 7.6% vs. 8.9% (HR = 0.85; 95% CI, 0.65-1.12) for 24 to 48 hours; 11.5% vs. 13.4% (HR = 0.83; 95% CI, 0.55-1.25) for 24 hours or fewer.

Liu and colleagues also wrote that moderate to severe bleeding occurrence was low across all three randomization time groups.

“This analysis suggests that these patients have a consistent benefit from receiving DAPT with clopidogrel and aspirin vs. aspirin alone when initiated within more than 24 hours to 48 hours and more than 48 hours to 72 hours as that when initiated within 24 hours or less,” they wrote.