Author + information
- Gennaro Sardella, MD∗ ( and )
- Simone Calcagno, MD
- ↵∗Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
We read with great interest the recently published paper on prasugrel or high-dose clopidogrel for high platelet reactivity (HPR) in the Journal (1). Using the Multiplate analyzer (Roche Diagnostics, Mannheim, Germany), the authors described how in patients with acute coronary syndrome (ACS), with HPR, switching therapy from clopidogrel to prasugrel reduces thrombotic and bleeding events to a level similar to those without HPR compared with high-dose clopidogrel.
As is known, the therapeutic effectiveness of clopidogrel is conditional upon its variability in its antiplatelet effect, which is influenced by numerous factors both genotypic (e.g., specific mutations in cytochrome P450 CYP2C19) and phenotypic (e.g., patient presentation with ACS). It has been demonstrated unequivocally that genotype testing for mutations in the clopidogrel metabolic pathway can identify patients who are poor responders and are at higher risk for subsequent ischemic events (2). Either increasing the dose of clopidogrel or substitution of other more potent agents not affected by the CYP2C19 pathway in patients with these mutations can lower platelet reactivity (PR) (3,4). Encouraged by these results, we also analyzed the superior efficacy of prasugrel to reduce the PR compared with a double dose of clopidogrel, and the correlation with genotype assessment. We showed the importance of CYP2C19*2 genotyping (5), describing the superiority of prasugrel over a double clopidogrel dose in patients carrying the CYP2C19*2 loss-of-function allele, while observing a similar efficacy of the 2 treatments in noncarriers of the CYP2C19*2 loss-of-function allele. PR was significantly lower (p = 0.045) for prasugrel in carriers, whereas no differences were observed in noncarriers (p = 0.575), but no one remained a poor responder to prasugrel (p = 0.003), whereas, despite a double clopidogrel dose, carriers always showed HPR.
It would be interesting to know the genotyping assay results of the all-comer patients enrolled in the 2 arms of this nonrandomized study to show the incidence of the CYP2C19*2 loss-of-function allele. In fact, the presence of this genotype variation could influence the superiority of prasugrel showed by Aradi et al. (1) over a high dose of clopidogrel. In our opinion, this is a central characteristic for a nonrandomized study to obtain 2 more similar populations to reach their aim and to evaluate the clinical and pharmacodynamic impact of using ADP–P2Y12 receptor inhibitors.
Finally, considering the high number of ST-segment elevation myocardial infarctions in this study, some concerns could arise about the clopidogrel utilization even if with a double dose and independently from PR responsiveness; in this subset of patients, the best choice could be the new antiplatelet agents, either prasugrel or ticagrelor.
- American College of Cardiology Foundation
- Aradi D.,
- Tornyos A.,
- Pintér T.,
- et al.
- Sardella G.,
- Calcagno S.,
- Mancone M.,
- et al.