Randomized Controlled Clinical Study of Clopidogrel with Indobufen or Aspirin in Minor Ischemic Stroke or High-risk Transient Ischemic Attack

Abstract

Abstract Background Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, along with the issues of aspirin and clopidogrel resistance, which contribute to bleeding events and recurrent episodes after the administration of traditional aspirin-clopidogrel dual antiplatelet therapy. Indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin. Some studies have demonstrated that the effectiveness of indobufen is equivalent to aspirin, and with a superior safety profile. However, no study has yet evaluated the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. Objective This study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. Methods Between February 2021 and February 2023, a randomized controlled clinical trial was conducted at a clinical center, with a total of 202 eligible patients enrolled. The trial was conducted in two stages: the first stage enrolled 30 cases to confirm safety, while the second stage observed the remaining 172 patients. Prospective data collection was carried out through paper-based case report forms, with follow-up conducted on the incidence of recurrent ischemic stroke or TIA within 3 months, mRS score, NIHSS score, and bleeding events within 3 months after onset for all enrolled patients. Results The group of patients receiving indobufen and clopidogrel exhibited significantly lower scores in modified Rankin Scale (mRS) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874–7.036, P < 0.0001). Endpoint events were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). Although the improvement rate of National Institutes of Health Stroke Scale (NIHSS) score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). Conclusion The combination of indobufen and clopidogrel has demonstrated superior efficacy and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA.