Ischemic stroke is a leading cause of morbidity and mortality worldwide. Current guidelines recommend dual antiplatelet therapy (DAPT) within a 24-hour time window and for patients with minimal stroke symptoms. However, the INSPIRES trial suggests that the benefits of DAPT may extend beyond these parameters. In this article, we will critically analyze the trial’s findings and discuss the implications for the management of ischemic stroke.
The INSPIRES trial enrolled individuals with minor ischemic stroke or high-risk transient ischemic attack (TIA) and administered DAPT within 72 hours of symptom onset. The results showed a significant decrease in new strokes within 90 days compared to aspirin alone. However, there was also a higher incidence of moderate-to-severe bleeding in the DAPT group.
This trial challenges the current recommendations for DAPT initiation and duration. The American Heart Association recently updated its guidelines to recommend a 21-day course of aspirin plus clopidogrel within 24 hours for patients with specific criteria. With the addition of the INSPIRES trial, there is evidence to support expanding the time window for DAPT to 72 hours. However, it is crucial to interpret this timing as “as soon as possible, but within 72 hours” and ensure the administration of a loading dose of clopidogrel.
The Clinical Impact of DAPT
Based on the rough calculation provided by Anthony Kim, MD, approximately 19 fewer strokes and 5 additional cases of moderate-to-severe bleeding can be expected for every 1,000 patients treated with clopidogrel-aspirin compared to aspirin alone. These numbers highlight the potential clinical impact of DAPT in reducing recurrent strokes but also draw attention to the increased bleeding risk.
It is worth noting that DAPT utilization in practice appears to be low, with recent data showing that only about 40% of eligible stroke patients received this therapy. This underutilization may be due to several factors, including physician adherence to guidelines, concern for bleeding complications, and limited awareness of the updated recommendations.
The INSPIRES trial has several limitations that should be considered. The study population predominantly consisted of Han Chinese individuals, which may limit the generalizability of the results to other ethnic groups. Additionally, the trial excluded patients with presumed cardioembolic stroke, those with moderate or severe stroke, and individuals already receiving DAPT or intensive statin therapy. These exclusions further restrict the applicability of the findings.
Future research should aim to address these limitations and explore the potential benefits and risks of other antiplatelet regimens. Additionally, the development of targeted antithrombotic agents may offer new options for stroke prevention with a more favorable balance of benefits and risks.
The INSPIRES trial provides valuable insights into the potential benefits of DAPT for ischemic stroke beyond the current treatment guidelines. Administering DAPT within 72 hours of symptom onset may reduce the risk of recurrent strokes, although the accompanying increase in bleeding events must be considered. Despite the underutilization of DAPT in practice, these findings suggest that expanding the treatment window could improve outcomes for patients with ischemic stroke. Further research and clinical trials are needed to refine the indications, timing, and duration of DAPT to maximize its benefits while minimizing the risks.