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

• Published in: Heart and vessels Vol. 35; no. 3; pp. 312 - 322
• Main Authors: Shimamatsu, Junichiro, Sasaki, Ken-ichiro, Katsuki, Yoshio, Kawasaki, Tomohiro, Murasato, Yoshinobu, Ajisaka, Hidehiko, Yokoi, Hiroyoshi, Tashiro, Hideki, Harada, Atsushi, Hirakawa, Yuji, Ishizaki, Yuta, Ishimatsu, Takashi, Kagiyama, Kotaro, Fukumoto, Yoshihiro, Kakuma, Tatsuyuki, Ueno, Takafumi
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.03.2020; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Aspirin; Aspirin - administration & dosage; Biomedical Engineering and Bioengineering; Cardiac Surgery; Cardiology; Cardiovascular disease; Cardiovascular diseases; Clopidogrel; Clopidogrel - administration & dosage; Clopidogrel - adverse effects; Clopidogrel - metabolism; Coronary artery disease; Coronary Artery Disease - blood; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - therapy; Cytochrome; Cytochrome P-450 CYP2C19 - genetics; Cytochrome P-450 CYP2C19 - metabolism; Cytochrome P450; Cytochromes P450; Drug delivery; Drug Resistance - genetics; Drug Substitution - adverse effects; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Female; Gene polymorphism; Genotypes; Heart diseases; Humans; Implantation; Implants; Japan; Male; Medicine; Medicine & Public Health; Middle Aged; Original; Original Article; Percutaneous Coronary Intervention - adverse effects; Percutaneous Coronary Intervention - instrumentation; Pharmacogenomic Variants; Platelet Aggregation - drug effects; Platelet Aggregation - genetics; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - metabolism; Platelets; Polymorphism; Polymorphism, Single Nucleotide; Prasugrel Hydrochloride - administration & dosage; Prasugrel Hydrochloride - adverse effects; Purinergic P2Y Receptor Antagonists - administration & dosage; Purinergic P2Y Receptor Antagonists - adverse effects; Purinergic P2Y Receptor Antagonists - metabolism; Risk Factors; Stents; Surgical implants; Switching; Therapy; Time Factors; Treatment Outcome; Vascular Surgery; Japan; Clopidogrel; Drug change; Percutaneous coronary intervention; Genetic polymorphism
• ISSN: 0910-8327; 1615-2573
• DOI: 10.1007/s00380-019-01499-7

Dual antiplatelet therapy (DAPT) with aspirin and P2Y 12 inhibitor is administered following percutaneous coronary intervention (PCI) with coronary stent implantation. Several studies have reported the effects of switching between P2Y 12 inhibitors on platelet reactivity (P2Y 12 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.