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African American Antiplatelet Stroke Prevention Study - AAASPS
Description:
The goal of the AAASPS trial was to determine the efficacy and safety of ticlopidine versus aspirin in preventing recurrent stroke, myocardial infarction (MI), or vascular death among African Americans with noncardioembolic ischemic stroke.
Hypothesis:
Ticlopidine (500 mg/d) is more effective than aspirin (650 mg/d) in preventing the composite outcome of recurrent stroke, MI, or vascular death among African Americans with noncardioembolic ischemic stroke who were followed up for up to two years.
Study Design
Study Design:
Patients Enrolled: 1,809
Mean Follow Up: 2 years
Mean Patient Age: Mean age 61 years
Female: 53%
Patient Populations:
African American race; age 29-85 years; noncardioembolic ischemic stroke with onset within 7-90 days; cranial computed tomographic scan or magnetic resonance imaging of the brain consistent with occurrence of the entry cerebral infarct; measurable neurological deficit that correlates at onset with entry cerebral infarct; informed consent; and availability to be followed up in an outpatient treatment program
Exclusions:
Transient ischemic attack, subarachnoid hemorrhage, cardiac source embolism, iatrogenic stroke, nonatherosclerotic stroke, postoperative stroke occurring within 30 days of operation, or carotid endarterectomy as primary treatment measure for entry cerebral infarct; mean arterial blood pressure >130 mm Hg on three consecutive days; modified Barthel index <10; history="" of="" dementia="" or="" neurodegenerative="" disease;="" severe="" comorbid="" condition="" judged="" to="" limit="" survival="" during="" two-year="" follow-up;="" enrollment="" in="" another="" clinical="" trial;="" allergy="" or="" sensitivity="" to="" study="" drugs;="" woman="" of="" childbearing="" potential;="" gastrointestinal="" tract="" bleeding,="" bleeding="" diathesis,="" or="" platelet="" or="" other="" hematologic="" abnormality="" during="" the="" prior="" year;="" hematuria="" or="" positive="" stool="" guaiac="" test="" related="" to="" major="" bleeding="" source;="" and="" prolonged="" prothrombin="" time="" or="" partial="" thromboplastin="" time,="" blood="" urea="" nitrogen="" level="">40 mg/dl, serum creatinine level >2.0 mg/dl, thrombocytopenia or neutropenia, or liver function tests ≥2 times the upper limit of normal
Primary Endpoints:
Composite of recurrent stroke, MI, or vascular death (defined as death due to ischemic or hemorrhagic stroke, MI, sudden death, pulmonary embolism, heart failure, visceral or limb infarction, or a vascular procedure or operation)
Secondary Endpoints:
Recurrent stroke or death; nonfatal or fatal stroke; recurrent stroke, MI, or death from all causes; vascular death; death from all causes; or MI
Drug/Procedures Used:
Patients were randomized to ticlopidine (500 mg/d) plus placebo aspirin (n=902) or aspirin (650 mg/d) plus placebo ticlopidine (n=907). The dose of aspirin was chosen at the start of the trial during the mid-1990s.
Principal Findings:
The trial was conducted over the course of nearly six years, and the blinded phase of the trial was discontinued after the Data Safety and Monitoring Board concluded that the futility analysis showed <1% chance="" that="" the="" ticlopidine="" arm="" would="" be="" superior="" compared="" with="" the="" aspirin="" arm="" if="" the="" trial="" were="" to="" continue="" to="" scheduled="">br />There was no difference in the primary composite outcome of recurrent stroke, MI, or vascular death between treatment arms (14.7% in the ticlopidine arm vs. 12.3% in the aspirin arm, hazard ratio 1.22, 95% confidence interval 0.94-1.57, p=0.12 by log-rank test). For the secondary outcome of fatal or nonfatal stroke, the Kaplan-Meier curves trended to be improved in the aspirin arm compared with the ticlopidine arm (11.9% in the ticlopidine arm vs. 9.5% in the aspirin arm, p=0.08 by log-rank test).
There was no difference in either of the other components of the composite endpoint: MI (0.9% vs. 0.9%, p=0.99) or vascular death (2.5% for ticlopidine vs. 2.1% for aspirin, p=0.52). There was also no difference in all-cause mortality (5.0% for ticlopidine vs. 4.4% for aspirin, p=0.56). Serious adverse events occurred in 29.9% of patients in the ticlopidine arm and 28.9% in the aspirin arm.
Interpretation:
Among African Americans with noncardioembolic ischemic stroke, ticlopidine was not associated with a difference in the primary composite endpoint of recurrent stroke, MI, or vascular death compared with aspirin during two years of follow-up, although the secondary endpoint of stroke trended to be improved in the aspirin arm.
The results of the study are unlike what was observed in the Ticlopidine Aspirin Stroke Study (TASS) and the Canadian American Ticlopidine Study (CATS), which both showed reductions in the primary endpoints associated with use of ticlopidine compared with aspirin among all patients. In the subset of African American patients in the TASS study, ticlopidine was also associated with a trend toward fewer events. Given the lack of benefit with ticlopidine, the authors suggest aspirin is a reasonable first choice prevention therapy in African American patients with noncardioembolic ischemic stroke.
References:
Gorelick PB, Richardson D, Kelly M, et al. Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial. JAMA 2003;289:2947-57.
Keywords: Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Cerebrovascular Disorders, Cerebral Infarction, Medical Futility, Ticlopidine, Informed Consent
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