Author + information
- Received October 13, 2010
- Accepted December 26, 2010
- Published online April 1, 2011.
- Dimitrios Alexopoulos, MD⁎,⁎ (, )
- Gerasimos Dimitropoulos, MD⁎,
- Periklis Davlouros, MD⁎,
- Ioanna Xanthopoulou, MD⁎,
- George Kassimis, MD⁎,
- Eleana F. Stavrou, PhD†,
- George Hahalis, MD⁎ and
- Aglaia Athanassiadou, PhD†
- ↵⁎Reprint requests and correspondence:
Dr. Dimitrios Alexopoulos, Department of Cardiology, Patras University Hospital, Rion 26500 Patras, Greece
Objectives The primary aim of the study was to determine the antiplatelet effects of prasugrel versus high-dose clopidogrel in patients with high on-treatment platelet reactivity (HTPR) after percutaneous coronary intervention (PCI) and, secondarily, their relation to cytochrome (CYP) 2C19*2 carriage.
Background High on-treatment platelet reactivity after clopidogrel administration after PCI is linked to the loss-of-function CYP2C19*2 allele and accompanied by an increased risk of adverse events.
Methods We performed a prospective, randomized, single-blind, crossover study of platelet inhibition by prasugrel 10 mg/day versus high-dose 150 mg/day clopidogrel in 71 (of 210 screened; 33.8%) post-PCI patients with HTPR. Platelet function was assessed by the VerifyNow assay (Accumetrics, San Diego, California), and real-time polymerase chain reaction genotyping was performed for CYP2C19*2 carriage.
Results The primary endpoint of platelet reactivity (measured in platelet reactivity units) at the end of the 2 treatment periods was lower after prasugrel compared with clopidogrel (least-squares estimates 129.4, 95% confidence interval [CI]: 111.1 to 147.7 versus 201.7, 95% CI: 183.2 to 220.2; p < 0.001). The least-squares mean difference between the 2 treatments was −122.9 (95% CI: −166.7 to −79.2, p < 0.001), and −47.5 (95% CI: −79.5 to −15.4, p = 0.004), in carriers and noncarriers of at least 1 mutant allele, respectively. The HTPR rates were lower for prasugrel than for clopidogrel, in all patients (7.5% vs. 35.8%, p < 0.001), in carriers (5.3% vs. 47.4%, p = 0.007), and in noncarriers (8.8% vs. 29.4%, p = 0.005), respectively.
Conclusions In patients with HTPR after PCI, prasugrel is more effective compared with high clopidogrel in reducing platelet reactivity, particularly in CYP2C19*2 carriers. Genotyping guidance might be helpful only in case an increased clopidogrel maintenance dose is considered. (Prasugrel Versus High Dose Clopidogrel in Clopidogrel Resistant Patients Post Percutaneous Coronary Intervention (PCI); NCT01109784)
The authors have reported that they have no relationships to disclose.
- Received October 13, 2010.
- Accepted December 26, 2010.
- American College of Cardiology Foundation