CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Marco Valgimigli, MD, PhD* and
Gianluca Campo, MD
* Cardiology Department, University of Ferrara-Arcispedale S. Anna, Corso Giovecca 203, Ferrara, Emilia Romagna 44100, Italy (Email: vlgmrc{at}unife.it).
We welcome the thoughtful comments by Dr. Serebruany to our recent publication on clopidogrel poor responsiveness in a broad population undergoing coronary stenting (1). Our major focus was to assess whether clopidogrel poor responders display inadequate platelet inhibition also after ticlopidine administration. We found that the great majority (83%) of patients who were clopidogrel nonresponders became responsive to ticlopidine, reaching a higher level of platelet inhibition (platelet aggregation [PA] 69 ± 15 vs. 44 ± 18; p < 0.01).
On the other hand, 23 patients who were responsive to clopidogrel showed resistance to ticlopidine and correspondingly less platelet inhibition with this drug (PA 46 ± 15 vs. 70 ± 15; p < 0.01).
When taken together our findings strongly suggest that poor responsiveness to currently commercially available thienopyridines may frequently be a drug-specific more than a class-effect mechanism. This conclusion holds particularly true in consideration that in the currently recommended regimen ticlopidine at steady state does not differ in terms of average inhibition of platelet aggregation than clopidogrel. This again emphasizes that individual drug response more than average potency of the 2 tested drugs explain our findings. In keeping with our findings, only a minority (15%) of poor responders to clopidogrel displayed a normal response to the same drug after doubling the dose in a recent phase II study (2).
We strongly disagree that "The major take-home message conveyed to the readership is that clopidogrel-treated patients may be switched to ticlopidine if ‘resistance’ is determined by the platelet tests." Indeed, in keeping with the conclusion statement of our recent paper, our findings, especially in the current pre-prasugrel era, should affect the design of future trials rather than clinical practice. The observation that ticlopidine, at the currently recommended dosage, unlike clopidogrel at double regimen, overcomes resistance to clopidogrel in the great majority of cases may prompt randomized controlled studies where standard care after stenting (i.e., clopidogrel 75 mg/day) is compared with tailored antiplatelet treatment (clopidogrel 150 mg/day in nonresponders to clopidogrel standard regimen or ticlopidine in nonresponders to clopidogrel double dose). Until such a study becomes available, both the risks and benefits of tailoring treatment based on target platelet inhibition will remain hypothetical.
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1. Campo G, Valgimigli M, Gemmati D, et al. Poor responsiveness to clopidogrel: drug-specific or class-effect mechanism?Evidence from a clopidogrel-to-ticlopidine crossover study. J Am Coll Cardiol 2007;50:1132-1137.[Abstract/Free Full Text]2. Angiolillo DJ, Shoemaker SB, Desai B, et al. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study Circulation 2007;115:708-716.[Abstract/Free Full Text]
Related Article
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Switching Thienopyridines: Hypothetical Versus Real Risks
- Victor L. Serebruany
J. Am. Coll. Cardiol. 2008 51: 775.
[Full Text]
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