DISCUSSION
Prasugrel has a potent, fast and consistent antiplatelet action and little is known about its impact on platelet function recovery [2]. Perioperative bleeding and blood transfusion requirement can be significantly increased during and after prasugrel therapy [8]. Hereby, we presented a patient with STEMI requiring an urgent CABG and in whom a complete platelet function recovery after prasugrel was detected by POC testing of platelet function. Despite the initial 60-mg loading dose along with a 10-mg daily maintenance dose over the course of 5 days, complete absence of biological response to prasugrel was demonstrated already 4 days after its discontinuation by preoperative TEG PlateletMapping.
Several factors can be associated with inadequate platelet inhibition by prasugrel such as poor patient compliance, drug absorption disturbances, underdosing and increased platelet turnover [9], while none of these was present in our case. Furthermore, patients with chronic renal failure requiring hemodialysis might have a relatively high rate of prasugrel hyporesponsiveness [10]; however, our patient had normal renal function. On the other hand, Fiore et al. have reported a case of stent thrombosis presenting with recurrent acute onset of chest pain despite being on DAPT including prasugrel and have found that this was related to the drug resistance [9]. Our patient did not have any signs nor predictors of prasugrel resistance. In addition, cytochrome (CYP) variants have been identified in some of the studies as predictors of prasugrel low response [11]. However, it was not possible to perform the genotyping for various CYP single-nucleotide polymorphisms to verify if our patient carried mutant alleles encoding enzymes involved in prasugrel metabolic pathway. In view of the interindividual variability in prasugrel response and platelet function recovery after cessation, we performed a TEG PlateletMapping and we demonstrated a complete recovery of platelet function already on the 4th day after prasugrel discontinuation. By means of POC testing of platelet function, we were able to reduce the waiting time and proceed with surgery.
In a recent randomized double-blinded study, Price et al. found that in aspirin-treated patients with CAD, the greater antiplatelet effect of prasugrel resulted in a more delayed recovery of platelet function as compared with clopidogrel [12]. The authors observed that antiplatelet effects of prasugrel had dissipated in ≥75% of patients 7 days after its cessation and these findings are consistent with current guidelines regarding the recommended waiting time for surgery after prasugrel discontinuation [12]. In a meta-analysis,Li et al. reported that prasugrel non-response was observed neither at 4 hours following loading dose in 566 patients nor at 9 days in 130 patients following maintenance dose [13]. Furthermore, among patients who underwent CABG in the TRITON-TIMI 38 trial, the rate of CABG-related bleeding was significantly higher with prasugrel compared with clopidogrel, and this increased risk persisted up to 7 days from the most recent dose of study drug [2].
Although current guidelines issue class IIb recommendations for preoperative platelet function assays, the use of preoperative platelet function monitoring to determine the timing of CABG in patients on antiplatelet therapy has been suggested in previous studies [7,14]. Recently, Mannaccio et al. demonstrated the benefits of an individualized preoperative waiting period in patients undergoing off-pump CABG [14]. Importantly, this study challenges current guidelines by showing that a strategy based on individualized POC platelet function measurements resulted in an overall 38% shortening of the recommended preoperative waiting period for patients on clopidogrel treatment and in a significant reduction of postoperative bleeding and blood product consumption.