Unstable angina, stroke, myocardial infarction and death in aspirin non-responders. A prospective, randomized trial. The ASCET (ASpirin non-responsiveness and Clopidogrel Endpoint Trial) design.
BACKGROUND
Aspirin is widely used as an antiplatelet drug in patients with coronary heart disease. Despite documented clinical benefit, many patients on aspirin still experience severe cardiovascular events. Several laboratory reports have shown lack of platelet inhibition in 5-40% of aspirin-treated patients, and the term aspirin resistance has been introduced. The clinical relevance of these laboratory findings is, however, still unknown. New antiplatelet drugs have been developed, and the adenosin diphosphate (ADP) receptor inhibitor clopidogrel has at least the same efficacy as aspirin with an acceptable safety profile. Laboratory methods for determination of platelet reactivity and treatment efficacy have been complicated and time consuming. New methodologies, like the PFA-100 system, have made such analyses more suitable for clinical use.


METHODS
In the ASCET study, 1000 patients with documented coronary heart disease will be randomized to either continued treatment with aspirin 160 mg/d or change to clopidogrel 75 mg/d after initial determination of their platelet reactivity while on aspirin treatment. Clinical endpoints will be recorded for at least 2 years and related to the initial aspirin response.
Pettersen
Alf-Age
AA
Department of Cardiology, Ullevål University Hospital, Oslo, Norway. alfaage@online.no
Seljeflot
Ingebjørg
I
Abdelnoor
Michael
M
Arnesen
Harald
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000453:epidemiology* / Q000401:mortality; D001241:Aspirin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000401:mortality; D009664:Norway / Q000453:epidemiology; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000401:mortality; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin