Poor Responsiveness to Clopidogrel: Drug-Specific or Class-Effect Mechanism?: Evidence From a Clopidogrel-to-Ticlopidine Crossover Study

ObjectivesThis study was designed to investigate whether poor responders to thienopyridines after clopidogrel remain so even after ticlopidine administration (class effect) or whether a drug-specific effect exists between currently available thienopyridines.BackgroundWhether clopidogrel poor responders also display inadequate platelet inhibition after ticlopidine administration remains undefined.MethodsPlatelet aggregation (PA) was measured in 143 patients, while they were taking aspirin, with light transmission aggregometry using adenosine diphosphate as an agonist at baseline (T0) and at clopidogrel steady state (T1). After T1,clopidogrel was stopped and substituted with ticlopidine. Then PA was assessed at ticlopidine steady state (T2). Resistance was defined as an absolute difference between T0and after-treatment (T1or T2) PA ≤10%.ResultsClopidogrel and ticlopidine responsiveness was normally distributed; PA at T1did not differ compared with T2. Thirty (21%) and 28 (19%) patients were clopidogrel and ticlopidine nonresponders, respectively. Only 5 patients (3.5%) were nonresponders to both clopidogrel and ticlopidine (class effect), whereas 25 patients (83%) who were clopidogrel nonresponders at T1were responsive to ticlopidine, reaching a higher level of platelet inhibition at T2(PA 69 ± 15 vs. 44 ± 18, p < 0.01) (drug-specific response). On the other hand, 23 patients who were responsive to clopidogrel showed resistance to ticlopidine at T2(PA 46 ± 15 vs. 70 ± 15, p < 0.01) (drug-specific response).ConclusionsPoor responsiveness to either clopidogrel or ticlopidine at steady state was common, whereas nonresponders to both drugs were relatively infrequent (3.5%, 95% confidence interval 1.5% to 7.9%), suggesting that poor response to thienopyridines may frequently be a drug-specific mechanism.