The very large clopidogrel for high Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) clinical trial concluded that dual antiplatelet therapy in stable ambulatory vasculopathic patients who are distant — at least 1 year post-MI, post-stroke — from their vascular event does not meaningfully reduce risk over monotherapy, and is associated with increased risk of bleeding. As convincing as this dataset is, it only addresses populations who are distant from their vascular event, rather than subjects who are in the higher risk period immediately following an acute event.

The Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial enrolled — within 24 hours of onset — Chinese subjects (n = 5170) who had sustained a minor ischemic stroke or transient ischemic attack (TIA). Subjects were randomized to treatment (double-blind) with low-dose aspirin (75 mg/d-300 mg/d) plus clopidogrel (300 mg on day 1, then 75 mg/d [CLO + ASA]) or low-dose aspirin plus placebo (ASA). The primary outcome was incidence of stroke (ischemic or hemorrhagic) over 90 days of follow-up.

CLO + ASA was associated with a 32% reduction in risk for stroke compared to aspirin alone. Risk for central nervous system hemorrhage was no different in the CLO + ASA group than ASA alone. In the immediate post-TIA/minor stroke period (up to 90 days), dual antiplatelet treatment meaningfully reduced risk without increasing bleeding.