OBJECTIVES: This 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. BACKGROUND: Whether clopidogrel poor responders also display inadequate platelet inhibition after ticlopidine administration remains undefined. METHODS: Platelet 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 T0 and after-treatment (T1 or T2) PA < or =10%. RESULTS: Clopidogrel and ticlopidine responsiveness was normally distributed; PA at T1 did 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 T1 were 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). CONCLUSIONS: Poor 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.

Poor responsiveness to clopidogrel: drug-specific or class-effect mechanism? Evidence from a clopidogrel-to-ticlopidine crossover study

CAMPO, Gianluca Calogero
Primo
;
VALGIMIGLI, Marco
Secondo
;
GEMMATI, Donato;PERCOCO, Giovanni;CATOZZI, Linda;FRANGIONE, Alice;FEDERICI, Federica;TEBALDI, Matteo;FERRARI, Roberto
Ultimo
2007

Abstract

OBJECTIVES: This 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. BACKGROUND: Whether clopidogrel poor responders also display inadequate platelet inhibition after ticlopidine administration remains undefined. METHODS: Platelet 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 T0 and after-treatment (T1 or T2) PA < or =10%. RESULTS: Clopidogrel and ticlopidine responsiveness was normally distributed; PA at T1 did 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 T1 were 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). CONCLUSIONS: Poor 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.
2007
Campo, Gianluca Calogero; Valgimigli, Marco; Gemmati, Donato; Percoco, Giovanni; Catozzi, Linda; Frangione, Alice; Federici, Federica; Ferrari, F; Tebaldi, Matteo; Luccarelli, S; Parrinello, G; Ferrari, Roberto
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0735109707020591-main.pdf

solo gestori archivio

Descrizione: Full text editoriale
Tipologia: Full text (versione editoriale)
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 296.17 kB
Formato Adobe PDF
296.17 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/522910
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 93
  • ???jsp.display-item.citation.isi??? 73
social impact