Antiplatelet Therapy

Aiya Almogaber, PharmD

A study published in the October 8, 2024, issue of Neurology revealed the benefits and risks of starting dual antiplatelet therapy (DAPT) with clopidogrel and aspirin within 72 hours of a mild ischemic stroke or transient ischemic attack (TIA).

Data from the INSPIRES trial showed that DAPT with clopidogrel and aspirin, initiated within 72 hours of a mild ischemic stroke or TIA, provided significant protection against major ischemic events, primarily within the first 3 weeks of treatment.

The study provided new insights into DAPT’s duration of benefits and risks, which may guide clinical practice. While a slight increase in moderate to severe bleeding risk was noted in the DAPT group, severe bleeding events were rare, suggesting early benefits may outweigh the risks.

“Attention should be paid to both the benefit and the bleeding risk of intensive antiplatelet therapy,” said Yuesong Pan, PhD, one of the study authors.

Stroke is a leading cause of disability and death worldwide, with mild ischemic strokes and TIA serving as key predictors of more severe future strokes.

Patients who experience a mild ischemic stroke or TIA face a heightened risk of subsequent strokes within the first 90 days—a critical period for intervention. This urgency has led to the widespread use of DAPT, combining clopidogrel and aspirin, to reduce risk.

The study findings address a significant gap in stroke prevention for high-risk patients following a mild ischemic stroke or TIA. Although DAPT is recommended, the ideal duration for balancing benefits and bleeding risks is unclear.

“Practitioners remain concerned about the possible increased bleeding associated with clopidogrel-aspirin and hope to find the optimal duration of antiplatelet therapy,” said Pan.

Study design

The INSPIRES trial, a large-scale, placebo-controlled study, was conducted to evaluate the safety and efficacy of DAPT with clopidogrel and aspirin for stroke prevention. The trial involved patients who had recently experienced a mild ischemic stroke or high-risk TIA of presumed atherosclerotic origin. Researchers analyzed data from 6,100 patients in China, conducted across 222 hospitals.

Participants were randomly assigned to receive either a 21-day regimen of clopidogrel and aspirin followed by clopidogrel alone for 90 days or aspirin alone for 90 days. The trial focused on patients treated within 72 hours of symptom onset, examining outcomes over 3 weeks and up to 90 days to identify the ideal DAPT duration to reduce recurrent stroke risk while managing bleeding risks.

During the first week, the DAPT group had a 1.42% absolute reduction in ischemic events compared with the aspirin-only group. This benefit continued in the second and third weeks before tapering off.

Clinical implications and recommendations

Findings from the trial data underscore the importance of promptly initiating DAPT within 72 hours of a mild ischemic stroke or high-risk TIA. The early benefits of clopidogrel-aspirin therapy suggest that short-term DAPT could be valuable in reducing recurrent stroke risk during this critical period.

While the study showed significant protective effects within the first 3 weeks, it also highlighted the need for careful monitoring due to bleeding risk. The data suggested that a 21-day course of DAPT balances ischemic protection with manageable hemorrhagic risks, supporting current guidelines.

These insights may encourage health care providers to adopt a more tailored approach, considering factors such as age, underlying health conditions, and individual bleeding risks before extending the duration of DAPT. For patients who have a particularly high-risk of recurrent stroke but low bleeding risk, a short DAPT course can offer a focused, evidence-backed preventive measure. ■