A little good...

M y grandmother used to say, " If a little'll do a little good, a lot'll do a lotta good. " Unfortunately, it is not that simple with antiplatelet agents. Many relevant facts are well established. In identifiable subgroups of patients who present with transient ischemic attacks (TIAs) or minor strokes, the risk of a subsequent stroke is high. Most of this risk is incurred during the first few days after a warning event. 2 Aspirin and other antiplatelet agents can lower the risk of secondary stroke by ≈12–22%. In patients with acute coronary syndromes, another throm-botic disorder, dual antiplatelet therapy, offers a greater risk reduction than aspirin alone, at the expense of increased hem-orrhagic risk. 6 In symptomatic and asymptomatic patients, dual antiplatelet therapy with clopidogrel and aspirin is better than aspirin alone in reducing microembolic signals detected by transcranial Doppler ultrasound as evidence of plaque-related embolism. The extended use of aspirin plus clopidogrel confers an increased risk of moderate-to-severe hemorrhage when compared with either agent alone. Early trials of dual antiplatelet therapy for secondary stroke prevention have shown either no benefit or a benefit that was counterbalanced by the increased risk of significant hemorrhage. 13 The designers of the Clopidogrel in High-Risk Patients with Acute Non-Disabling Cerebrovascular Events (CHANCE) trial of dual antiplatelet therapy for secondary stroke prevention sought to enhance relative benefit by focusing on high-risk patients during their period of highest risk. 14 They took advantage of the clustering of risk in the period immediately after a TIA by enrolling patients early (within 24 hours) after a TIA or minor stroke and by limiting treatment with dual agents to the first 3 weeks after an event, thus limiting the exposure risk for hemorrhagic complications. With this strategy , the CHANCE trial succeeded where other studies had failed. In the CHANCE trial, the dual-agent versus single-agent patients diverged in favor of the dual-agent group within the first few days of follow-up, and, after that, the rates of the accumulated strokes of the two groups remained equal. Therefore, with only 21 days of dual therapy, the dual-agent group retained its advantage at 3 months. The CHANCE trial was well designed and well executed. The main questions that remain concern the reproducibility and generalizability of this result. The question of generalizability primarily concerns the population studied in the CHANCE trial. The CHANCE patients were enrolled in China where the …