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

Junichiro Shimamatsu,Takafumi Ueno,Tomohiro Kawasaki,Yoshio Katsuki,Yoshinobu Murasato,Hideki Tashiro,Hidehiko Ajisaka,Kotaro Kagiyama,Ken-Ichiro Sasaki,Yuji Hirakawa,Yoshihiro Fukumoto,Atsushi Harada,Takashi Ishimatsu,Hiroyoshi Yokoi,Yuta Ishizaki,Tatsuyuki Kakuma

doi:10.1007/s00380-019-01499-7

Abstract

Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitor is administered following percutaneous coronary intervention (PCI) with coronary stent implantation. Several studies have reported the effects of switching between P2Y12 inhibitors on platelet reactivity (P2Y12 reaction units: PRU), from acute to late phase after PCI. However, the effect of switching at very late phase is unknown. This study examined the effect on PRU in Japanese coronary heart disease patients with long-term DAPT (aspirin + clopidogrel) when switching from clopidogrel to prasugrel. Ninety-six patients were enrolled in this study. The median DAPT duration at enrollment was 1824.0 days. Twenty-three patients with PRU ≥ 208 at enrollment were randomly assigned into either continuing to receive clopidogrel (Continued Group; n = 11) or switching to prasugrel (Switched Group; n = 12). The primary endpoint was the rate of patients who achieved PRU < 208 at the end of 12 weeks of treatment, which was significantly higher in Switched Group relative to Continued Group (90.0% vs. 36.4%; P = 0.024). The secondary endpoint was the PRU at week 12 in groups subdivided according to cytochrome P450 (CYP) 2C19 genotypes. At week 12, extensive metabolizers (EM Group) had 202.3 ± 60.0 and 174.5 ± 22.3 in Continued Group and Switched Group (P = 0.591), respectively; intermediate and poor metabolizers (non-EM Group) had 229.4 ± 36.9 and 148.4 ± 48.4 in Continued Group and Switched Group (P = 0.002), respectively. The PRU for non-EM Group was significantly reduced in Switched Group. Thus, for patients with long-term DAPT (aspirin + clopidogrel) after PCI with coronary stent implantation, switching from clopidogrel to prasugrel resulted in a stable reduction in PRU, regardless of CYP2C19 polymorphism.

Highlights

The guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitor to prevent major adverse cardiovascular events, such as stent thrombosis and reinfarction, in patients after percutaneous coronary intervention (PCI) with coronary stent implantation [1,2,3]
The ADAPTDES study reported that the incidence of stent thrombosis or myocardial infarction was significantly higher in patients with P2Y12 reaction units (PRU) > 208 after successful PCI, compared to patients with PRU ≤ 208 [11, 12]; and, considering such, the platelet function testing may not as insignificant as claimed
The baseline PRU according to CYP2C19 polymorphism was 143.5 ± 59.7 in extensive metabolizers (EM), 173.3 ± 56.3 in intermediate metabolizers (IM) and 206.4 ± 49.8 in poor metabolizers (PM), indicating that the PRU were significantly higher in IM and PM, compared to EM

Summary

Introduction

The guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitor to prevent major adverse cardiovascular events, such as stent thrombosis and reinfarction, in patients after percutaneous coronary intervention (PCI) with coronary stent implantation [1,2,3]. The P2Y12 reaction units (PRU), an index of antiplatelet effects of P2Y12 inhibitors, are reported to be a relevant factor associated with cardiovascular events [9, 10]. The ADAPTDES study reported that the incidence of stent thrombosis or myocardial infarction was significantly higher in patients with PRU > 208 after successful PCI, compared to patients with PRU ≤ 208 [11, 12]; and, considering such, the platelet function testing may not as insignificant as claimed

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