HomeCirculation: Cardiovascular InterventionsVol. 6, No. 1Letter by Alexopoulos et al Regarding Article, “Pharmacodynamic Effect of Switching Therapy in Patients With High On-Treatment Platelet Reactivity and Genotype Variation With High Clopidogrel Dose Versus Prasugrel: The RESET GENE Trial” Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBLetter by Alexopoulos et al Regarding Article, “Pharmacodynamic Effect of Switching Therapy in Patients With High On-Treatment Platelet Reactivity and Genotype Variation With High Clopidogrel Dose Versus Prasugrel: The RESET GENE Trial” Dimitrios Alexopoulos, MD, FESC and Ioanna Xanthopoulou, MD Dimitrios AlexopoulosDimitrios Alexopoulos Cardiology DepartmentPatras University HospitalPatras, Greece Search for more papers by this author and Ioanna XanthopoulouIoanna Xanthopoulou Cardiology DepartmentPatras University HospitalPatras, Greece Search for more papers by this author Originally published1 Feb 2013https://doi.org/10.1161/CIRCINTERVENTIONS.112.975953Circulation: Cardiovascular Interventions. 2013;6:e11To the Editor:We read with great interest the recently published RESET GENE study in Circulation: Cardiovascular Interventions.1 Using the Multiplate Analyzer, the authors described that in stable patients exhibiting high on-clopidogrel treatment platelet reactivity (HTPR) post-percutaneous coronary intervention, prasugrel 10 mg QD provided a better than clopidogrel 150 mg QD platelet inhibition. They attributed this result to the superiority of prasugrel over double clopidogrel in patients carrying the CYP2C19*2 loss-of-function allele, while describing a similar efficacy of the 2 treatments in noncarriers of the CYP2C19*2 loss-of-function allele. These findings partially agree with our study using the VerifyNow assay in a more than double the size population, mostly with recent ACS, and presenting with HTPR post-percutaneous coronary intervention, comparing prasugrel 10 mg QD versus clopidogrel 150 mg QD who were genotyped as well.2 We described that prasugrel was significantly more effective in noncarriers as well with a platelet reactivity least-squares mean difference between the 2 treatments of –47.5 platelet reaction units (95% confidence interval, –79.5 to –15.4; P=0.004). Although the authors recognize that their study was not powered for an additive genetic model, reporting that noncarriers show a similar response after testing with either drug might be an erroneous conclusion most likely caused by the small number of patients.In the study by Sardella et al1, nonresponders following therapy with prasugrel were not found. However, it should be pointed out that HTPR while on prasugrel does exist3 and it was present in 7.5% of our patients with HTPR on clopidogrel when they switched over to prasugrel.2 The reported absence of no response while on prasugrel most likely reflects the small study size, definition of HTPR, method used, or the stability of the studied population.In the studied population, 14 patients had at least 1 CYP2C19*2 loss-of-function allele, with 2 of them being homozygotes. After the ELEVATE TIMI 56 study, an effort to overcome HTPR in homozygotes by increasing clopidogrel to 150 mg is most likely purposeless.4 It would be interesting to know whether the superiority of prasugrel over double clopidogrel is still present if one confines the analysis to heterozygotes only, eg, after excluding the 2 homozygotes.In addition, methodological clarification may help the reader to better understand the study findings. Because the Muliplate Analyzer results are expressed in area under the aggregation curve (AUC), it would be interesting to know how the authors calculated the inhibition of platelet aggregation reported as a percentage. This parameter was not defined in their methodology. The HTPR rates also are confusing because it seems that the authors used 2 different definitions for HTPR (1) AUC >450 and (2) AUC >450 and inhibition of platelet aggregation >20%.We believe that the main limitation of the tested strategies is the lack of any potential clinical significance in stable patients undergoing percutaneous coronary intervention. After the testing platelet reactivity in patients undergoing elective stent placement on clopidogrel to guide alternative therapy with prasugrel (TRIGGER-Percutaneous Coronary Intervention) results,5 overcoming HTPR by any means in this low risk population is of highly questionable benefit.Dimitrios Alexopoulos, MD, FESCIoanna Xanthopoulou, MDCardiology DepartmentPatras University HospitalPatras, GreeceDisclosuresDr Alexopoulos reports receipt of speaker fees from AstraZeneca.
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Oct 4, 2024
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