1. ANTIPLATELET TREATMENT IN PATIENTS WHO HAVE AN ISCHEMIC STROKE WHILE TAKING ASPIRIN Konstantinos Tziomalos, Stella D. Bouziana, Marianna Spanou, Stavroula Kostaki, Maria Papadopoulou, Vasilios Giampatzis, Maria Tsopozidi, Stella-Maria Angelopoulou, Christos Savopoulos, Apostolos I. Hatzitolios First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece 1

2. Introduction - Objectives The optimal antiplatelet treatment in patients who have an ischemic stroke while taking aspirin is unknown In patients with cardiovascular disease, increasing the dose of aspirin is associated with higher risk of gastrointestinal bleeding without further reduction in the risk of cardiovascular events In the CAPRIE trial (n = 19,185), clopidogrel was not more effective than aspirin in reducing cardiovascular events in patients with a history of ischemic stroke In the CHARISMA trial (n = 12,153), clopidogrel plus aspirin reduced cardiovascular events more than aspirin monotherapy in patients with established cardiovascular disease but also increased the risk of major bleeding The aim of the present study was to compare two strategies in patients who have an ischemic stroke while taking aspirin, i.e. continuing aspirin at the same dose or switching to clopidogrel monotherapy BMJ 2002;324:71-86 Lancet 1996;348:1329-39 N Engl J Med 2006;354:1706-17 2

3. Patients and methods We prospectively studied 436 patients (39.2% males, age 78.6±6.7 years) who were consecutively discharged after acute ischemic stroke One year after discharge, patients and/or their relatives were contacted by phone and the incidence of nonfatal ischemic stroke, nonfatal myocardial infarction, cardiovascular death and all-cause mortality were recorded 3

4. Results (I) – Characteristics of patients at discharge At admission, 41 patients (9.4% of the total study population) were being treated with aspirin 100 mg/day and had sinus rhythm At discharge, these patients were prescribed aspirin 100 mg/day (n=12) or clopidogrel (n=29) 4 Patients treated with aspirin (n = 12) Patients treated with clopidogrel (n = 29) p Age (years)78.6±4.277.4±8.70.647 Males (%)50.0 1.000 Hypertension (%)100.069.20.038 Diabetes mellitus (%)9.150.00.019 Coronary heart disease (%)50.0 1.000 Smoking (current/past, %)8.3/8.310.3/24.10.566 Obesity (%)0.038.90.031 LDL cholesterol (mg/dl)107±2894±270.250 HDL cholesterol (mg/dl)41±1540±130.787 Triglycerides (mg/dl)112±59125±450.520 Modified Rankin scale2.1±1.82.1±1.90.987

5. Results (II) – Outcome of patients at 1 year after discharge 5 Patients treated with aspirin (n = 12) Patients treated with clopidogrel (n = 29) p Nonfatal ischemic stroke (%)27.325.00.890 Nonfatal myocardial infarction (%)18.25.00.235 Cardiovascular mortality (%)10.010.50.965 All-cause mortality (%)27.320.00.643

6. Conclusions In patients who suffer ischemic stroke despite aspirin treatment, switching to clopidogrel appears to be more appropriate than continuing aspirin at the same dose 6