High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel

Abstract

BackgroundPrasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited.ObjectivesTo determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS).PatientsPatients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors.ResultsAt 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively.ConclusionsRoutine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit.Trial RegistrationClinicalTrials.gov NCT01339026

Prevalence and predictors of high-on treatment platelet reactivity during prasugrel treatment in patients with acute coronary syndrome undergoing stent implantation

“…However, the magnitude of the problem of HRPR on prasugrel treatment is still largely undefined, with its rate varying among studies according to the methods and definitions applied [13,36].…”

Impact of Double Loading Regimen of Clopidogrel on Final Angiographic Results, Incidence of Upper Gastrointestinal Bleeding and Clinical Outcomes in Patients with STEMI Undergoing Primary Coronary Intervention

“…Double Loading Regimen of clopidogrel did not confer additional benefits on short-term and long-term outcomes in Asian patients with STEMI undergoing primary PCI: Clopidogrel has emerged as a mainstay in the management of patients with acute arterial occlusive syndrome over the past decade, as well as a principal component of PCI pharmacotherapy. [18][19][20][21][22][23] However, growing amounts of data have recently shown that poor response (i.e., drug resistance) to clopidogrel as measured by platelet reactivity units or with VerifyNow assay measured in P2Y12 reaction units (PRU) 31,32) occurs in some ACS patients in real-world clinical practice. [24][25][26] This situ-ation, resulting in high-risk thromboembolic events, undoubtedly causes poorer prognostic outcome in patients with ACS undergoing PCI.…”

“…[24][25][26] This situ-ation, resulting in high-risk thromboembolic events, undoubtedly causes poorer prognostic outcome in patients with ACS undergoing PCI. The results of these experimental and clinical studies [24][25][26]31,32) raise the question of whether a double dose regimen (i.e., 600 mg) of clopidogrel may improve clinical outcomes in ACS patients undergoing PCI. 33,34) However, other clinical trials 24,35) did not find the additional benefit of double regimen of clopidogrel as measured by angiographic findings and clinical outcome as compared to standard loading regimen (i.e., 300 mg) of clopidogrel.…”

“…Additionally, in gene polymorphism CYP2C19 *2 carriers, ticargrelor or prasugrel, should be considered in Asian STEMI patients because they have been established to have a more potent effect on inhibiting platelet reactivity than that of the clopidogrel. 31,32) Higher incidence of UGIB in Asian patients than in Western patients after receiving antiplatelet therapy: The incidence of major bleeding and UGIB is always a great concern in the treatment of ACS patients. 18,24,39,40) In the CAPRIE trial, reports of gastrointestinal hemorrhage were 1.99% with clopidogrel and 2.66% with aspirin, respectively.…”

Platelets as a novel source of Gremlin-1: Implications for thromboinflammation

“…The area under the aggregation curve (AUC) was used as a measure of the overall platelet aggregation. Tests were performed within 30 min after taking blood (14).…”