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.