Antiplatelet effects of prasugrel vs. double clopidogrel in patients on hemodialysis and with high on‐treatment platelet reactivity

Abstract

Antiplatelet effects of prasugrel vs. double clopidogrel in patients on hemodialysis and with high on-treatment platelet reactivity. J Thromb Haemost 2011; 9: 2379-85.Summary. Background: High on-treatment platelet reactivity (HTPR) is frequent in patients on hemodialysis (HD) receiving clopidrogel. Objectives: The primary aim of this study was to determine the antiplatelet effects of prasugrel vs. high-dose clopidogrel in patients on HD with HTPR. Patients/Methods: We performed a prospective, single-center, single-blind, investigator-initiated, randomized, crossover study to compare platelet inhibition by prasugrel 10 mg day 3), P < 0.001). The LS mean differences between the two treatments were ) 113.4 PRU (95% CI ) 152.9 to ) 73.8, P < 0.001) and ) 163.8 PRU (95% CI ) 218.1 to ) 109.2, P < 0.001) in non-carriers and carriers of at least one CYP2C19*2 allele, respectively. HTPR rates were lower for prasugrel than clopidogrel, in all patients (19% vs. 85.7%, P < 0.001) and in non-carriers (25.7% vs. 80%, P = 0.003). All carriers continued to show HTPR while receiving high-dose clopidogrel, but none showed it while receiving prasugrel. Conclusions: In HD patients exhibiting HTPR following standard clopidogrel treatment, prasugrel 10 mg day -1 is significantly more efficient than doubling the clopidogrel dosage in achieving adequate platelet inhibition. Neither effect seems to be influenced by carriage of the loss-offunction CYP2C19*2 allele.

Platelet‐reactivity tests identify patients at risk of secondary cardiovascular events: a systematic review and meta‐analysis

“…Increasing the clopidogrel dose reduces HCPR [32,[47][48][49][50][51]. Switching to prasugrel [32,49,50], ticlopidine [32], ticagrelor [52] or cilostazol [47] has the same effect.…”

“…Switching to prasugrel [32,49,50], ticlopidine [32], ticagrelor [52] or cilostazol [47] has the same effect. However, none of these options is suitable for the treatment of HCPR in all patients.…”

“…However, none of these options is suitable for the treatment of HCPR in all patients. Increasing the clopidogrel dose was less effective in reducing platelet activity than the use of alternative platelet inhibitors, such as prasugrel [49,50,53], ticagrelor [52], or cilostazol [47]. An increased clopidogrel dose reduced the numbers of early and late CVEs in VASP-assay-defined HCPR patients undergoing non-emergent PCI [54][55][56].…”

P2Y12 Receptor Inhibitors in Acute Coronary Syndromes: From the Research Laboratory to the Clinic and Vice Versa

“…The HPR prevalence is very high, escalating with increasing stages of disease severity and predictive of adverse events after PCI [41,42]. In patients on hemodialysis, prasugrel or ticagrelor may overcome HPR, although no outcome data on efficacy and particularly safety are available in this high-risk cohort of patients [43,44]. In the clinical field, in patients with a creatinine clearance <60 ml/min - excluding hemodialysis - data from TRITON TIMI-38 showed a reduction in the primary end point of cardiovascular death, MI, an stroke by a nonsignificant 14% with prasugrel compared to clopidogrel [22].…”

Variability and treatment of high on-prasugrel platelet reactivity in patients with initial high on-clopidogrel platelet reactivity

“…Cases of HTPR while on prasugrel have scarcely been reported, with minimal data on its variability over time and ways for its treatment [2][3][4][5]. We describe our experience in patients who exhibited HTPR while on 10 mg maintenance dose of prasugrel, its variability over time and strategies to overcome.During a 15 month period and in the context of 3 randomized studies assessing the pharmacodynamic effects of prasugrel 10 mg vs clopidogrel 150 mg daily in patients with HTPR while on clopidogrel, we have performed platelet function testing using the VerifyNow (Accumetrics Inc., San Diego, CA, USA) point-of-care P2Y12 assay, as previously described [6][7][8]. Results are reported as P2Y12 reaction units (PRU) with a value ≥ 235 considered as an indication of HTPR [6].…”