Temporal Changes in Platelet Response in Acute Coronary Syndrome Patients With Prasugrel and Clopidogrel After Stent Implantation

Abstract

Background:Prasugrel has been shown to provide more potency and less variability than clopidogrel, but its potential temporal variability has not been described. Methods and Results:We conducted a prospective open-label study, evaluating platelet reactivity overtime in acute coronary syndrome (ACS) patients on aspirin and clopidogrel (n=60) or prasugrel (n=61), after a percutaneous coronary intervention (PCI). Blood samples were taken at discharge and at 3 and 6 months. Platelet function tests included VerifyNow (VN-P2Y12), and Multiplate Aggregometry (MEA). By means of VN-P2Y12, prasugrel patients displayed significantly (P<0.001) higher platelet inhibition than clopidogrel patients over time, although there were not significant differences using MEA. Prasugrel patients showed higher platelet inhibition at baseline than at 3 months (59.3±8.1 vs. 105.0±49.2; P<0.001), without significant change at 6 months (107.9±72.0; P=0.919 vs. 3 months). Clopidogrel patients showed a similar trend (160.1±65.1, 184.8±62.7 and 185.0±53.3; baseline vs. 3 months P=0.060; 3 months vs. 6 months P=0.974). High platelet reactivity (HPR) was shown in 16.3% prasugrel patients, with no patient consistently remaining in HPR over time. HPR was detected in 36.6% of the clopidogrel patients, being consistently observed in 15.0% of them. Low platelet reactivity (LPR) was detected in 60.5% prasugrel and 9.8% clopidogrel patients. Conclusions:Prasugrel patients showed less temporal variation than patients on clopidogrel in terms of HPR. In contrast, higher variability in LPR was detected in prasugrel patients for up to 6 months' follow-up.

Individual long-term variation of platelet reactivity in patients with dual antiplatelet therapy after myocardial infarction

“…The change occurred in both stable patients and NSTEACS patients (15). Supporting our findings, a recently published paper reported that 36.6% of clopidogrel-treated patients had HPR status at any of three time-points over 6 months (at discharge, 3 and 6 months) (18). In our study, 31.2% off the patients were HPR at day 8 or at 6 months.…”

“…However, the trials performed so far have given limited support to a personalized antiplatelet treatment strategy based on platelet activity testing (9)(10)(11)(12). While inter-individual variation has been well studied, less attention has been paid to intra-individual variation over time, and the few reports to date have given contradictory results (13)(14)(15)(16)(17)(18)(19). A concept of tailored treatment based on a single measurement assumes that a patient can be correctly defined as a high, optimal or low responder to clopidogrel treatment.…”

Is a personalized pharmacotherapeutic approach closed for acute coronary syndrome?

“…Optimal medical therapy in ACS patients includes dual-antiplatelet therapy (DAPT) with aspirin and a P2Y 12 inhibitor, together with high-dose statins, and if appropriate beta-blockers, and renin-angiotensinaldosterone system inhibitors. However, this evidence-based optimal therapy is often underused, probably due to underestimating the risk and treatment benefits in these patients [2][3][4]. The role of personalized medicine is increasingly recognized by the clinician, health systems, and pharmaceutical industries to improve net clinical outcome.…”

Periprocedural Variability of Platelet Functions in Carotid Artery Stenting: An Analysis Using VerifyNow

“…4) Many studies using VerifyNow have provided useful evidence about hypo-response to aspirin or clopidogrel, [4][5][6][7][8][9][10][11][13][14][15][16][17] as well as hyper-response to clopidogrel. 4,13,18) Recently, dynamic variability in response to clopidogrel after endovascular treatment has been reported 10,[18][19][20][21][22][23] ; however, individual changes in platelet functions in the short period under DAPT have not been described yet. Using the VerifyNow assay, this study aimed to reveal how and why platelet functions in CAS patients change in the periprocedural period.…”

“…ARU: aspirin reaction unit; NASCET: North American Symptomatic Carotid Endarterectomy TrialIndividual ARU and PRU changes and their predictorsMultiple repeat measurements of the VerifyNow assay in healthy volunteers who did not take antiplatelet drugs revealed that PRU values varied widely intraindividually in contrast to ARU values 26). There are some reports regarding the variability of ARU and PRU values during periprocedural periods of endovascular treatments,10,18,[21][22][23] but most investigated the relatively long-term variability such as more than 1 week to 6 months after treatment.10,18,21) Khanna et al measured ARU and PRU values in patients after…”