Which patients with an ischemic stroke are likely to be helped or harmed by early aspirin treatment?

BACKGROUND: Long-term aspirin use is of demonstrated benefit in the prevention of ischemic stroke and death in high-risk patients. The Chinese Acute Stroke Trial (CAST) and the International Stroke Trial (IST) showed that beginning aspirin promptly after an ischemic stroke reduces the immediate risk of recurrent stroke and death. The authors of this paper pooled the results of these 2 trials to evaluate outcomes in different subgroups.

POPULATION STUDIED: The IST included 19,435 patients from 36 countries across Europe, Asia, North America, and South America, while the CAST reported on 20,655 patients from China. All of the patients presented within 48 hours of symptom onset (or sleep onset if the stroke occurred while asleep). The patients were included in both studies if their physician determined that there were no contraindications to aspirin treatment but he or she was uncertain whether aspirin treatment was indicated. Patients with a clear reason to receive aspirin were excluded, such as patients with possible cardiac ischemia, as were those with a contraindication to aspirin treatment. Contraindications were determined by the responsible physician rather than a protocol and were generally based on the likelihood of an increased risk of adverse effects (eg, aspirin sensitivity, already orally anticoagulated, or recent serious gastric bleeding) or the likelihood of little benefit (eg, severe preexisting disability or symptoms likely to quickly resolve). The mean age of patients was 67 years; 12% had atrial fibrillation, and 15% had a systolic blood pressure of at least 190 mm Hg

STUDY DESIGN AND VALIDITY: The CAST used concealed randomization, blinding, and placebo control. Although most patients had computed tomography (CT) scanning before randomization, only comatose patients were required to have CT scans to exclude intracranial hemorrhage. Aspirin (160 mg film-coated) or placebo was given for 4 weeks or until earlier hospital discharge or death. In the CAST trial, 219 patients in the aspirin group and 232 in the placebo group lacked follow-up data and were excluded from the analysis. The IST used concealed randomization but lacked placebo control. Aspirin in a 300-mg dose was given for 2 weeks or until earlier hospital discharge or death. Half of the patients in the IST also received subcutaneous heparin. Only 2 patients were lost to follow-up in the IST. Heterogeneity between studies was appropriately evaluated and found to be nonsignificant. The Mantel-Haenszel chi-square method was used to combine data from the studies, which is appropriate when the studies are homogenous. No racial subgroups were analyzed, and it would be helpful to confirm that this benefit holds true across these subgroups.

OUTCOMES MEASURED: The primary outcomes were the rates of recurrent ischemic stroke, hemorraghic stroke, any stroke, death without further stroke, or the combined outcome (any of these). These outcomes were presented for different patient subgroups based on the hours since stroke onset, age, sex, level of consciousness, presence of atrial fibrillation, whether CT was performed, CT findings, initial systolic blood pressure, stroke syndrome (lacunar vs nonlacunar), score on a prognostic index, and whether the patient received heparin.

RESULTS: The rates of recurrent ischemic stroke (1.6% vs 2.3%; P <.001; number needed to treat [NNT]=143) and death without further stroke (5.0% vs 5.4%; P=.05; NNT=250) were both significantly lower in the aspirin treatment group. The risk of hemorrhagic stroke or hemorrhagic transformation of the original stroke was not significantly increased by use of aspirin (1.0% vs 0.8%; P=.07%). There was a significant decrease in the combined outcome of further stroke or death (8.2% vs 9.1%; P=.001; NNT=111). The subgroup analysis did not reveal any characteristic that defined a group that varied significantly in the degree of benefit or harm from the entire treated group.