Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies

Abstract

Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3.75 mg) adjusted for Japanese patients, evaluate the risk factors for bleeding in Japanese patients, and examine whether patients with a bleeding event are at increased risk of recurrent bleeding. This review covers published data and new analyses of the PRASFIT (PRASugrel compared with clopidogrel For Japanese patIenTs) trials of patients undergoing PCI for acute coronary syndrome or elective reasons. The bleeding risk with prasugrel was similar to that observed with the standard dose of clopidogrel (300/75 mg), including when bleeding events were re-classified using the Bleeding Academic Research Consortium criteria. The pharmacodynamics of prasugrel was not associated with the risk of bleeding events. The main risk factors for bleeding events were female sex, low body weight, advanced age, and presence of diabetes mellitus. Use of a radial puncture site was associated with a lower risk of bleeding during PCI than a femoral puncture site. Finally, the frequency and severity of recurrent bleeding events during continued treatment were similar between prasugrel and clopidogrel. In summary, this review provides important insights into the risk and types of bleeding events in prasugrel-treated patients.

Prasugrel effectively reduces the platelet reactivity units in patients with genetically metabolic dysfunction of cytochrome P450 2C19 who are treated with long-term dual antiplatelet therapy after undergoing drug-eluting stent implantation

“…Risk of bleeding events is a recent topic, often mentioned with respect to antiplatelet agents in the field of PCI. The PRASFIT-ACS and PRASFIT-Elective studies conducted in Japan reported that risk of bleeding events was female sex, age ≥ 75 years, and weight ≤ 50 kg [28]. The present study also found that patients with PRU ≥ 208 after longterm DAPT (aspirin + clopidogrel) included more females, more with advanced age and lower body weight, compared to those with PRU < 208.…”

Perioperative management and monitoring of antiplatelet agents: a focused review on aspirin and P2Y12inhibitors

“…The incidence of MACE was numerically lower with prasugrel compared to clopidogrel, although the difference was not statistically significant (9.4% vs. 11.8%; hazard ratio 0.77; 95% CI 0.56–1.07). The incidence of the composite of major, minor, and clinically-relevant bleeding was 9.6% in both prasugrel and clopidogrel groups [29]. In the whole cohort (n = 1,363), pharmacodynamics of prasugrel (i.e., extent of platelet inhibition) was not found to be a bleeding risk factor.…”

“…In the whole cohort (n = 1,363), pharmacodynamics of prasugrel (i.e., extent of platelet inhibition) was not found to be a bleeding risk factor. The key bleeding risk factors were female gender, low body weight (≤ 50 kg), advanced age (≥ 75-year-old), and diabetes mellitus in this Japanese cohort [29]. …”

“…PRU values were lower with prasugrel than clopidogrel at 24 h (147 ± 80 vs. 261 ± 57, P < 0.001), and in 2 weeks (171 ± 67 vs. 221 ± 70, P = 0.005). No specific threshold PRU values predictive of non-CABG major bleeding events were found, but bleeding risks were associated with females, low body weight (≤ 50 kg), advanced age (≥ 75-year-old), and diabetes mellitus [29]. …”

“…The safety end points of this study indicated that death and cerebral infarction were increased in the rFVIIa cohorts relative to the placebo (odds ratio 1.67; 95% CI 0.50–5.47), although re-exploration and allogeneic transfusion rates were reduced by rFVIIa [72]. Advanced age (≥ 75-year-old) is an important risk factor for both P2Y 12 inhibitor related bleeding [29], but it is also associated with rFVIIa-related thrombosis [70]. It is thus important to carefully consider the risk/benefit ratio of these interventions in the elderly.…”