Key result
Switching to prasugrel increases optimal platelet reactivity to ~90% versus continuing clopidogrel.
Why the study?
The effect of switching from clopidogrel to prasugrel at very late phase after PCI was unknown.
Does switching from clopidogrel to prasugrel improve the rate of patients achieving PRU < 208 in Japanese coronary heart disease patients on long-term DAPT with high on-treatment platelet reactivity?
RCT (n=96)
Open-label
1:1 via interactive web response system (IWRS) and minimization method using PRU as an allocation adjustment factor
Yes
Does switching from clopidogrel to prasugrel improve the rate of patients achieving PRU < 208 in Japanese coronary heart disease patients on long-term DAPT with high on-treatment platelet reactivity?
Absolute Event Rate: 90% vs 36.4%
p-value: p=0.024
Switching from clopidogrel to prasugrel in patients on long-term DAPT with high platelet reactivity effectively reduces platelet reactivity, particularly in those with CYP2C19 loss-of-function alleles.
Supports prasugrel switch to optimize reactivity in high on-treatment patients; extends RCT evidence to Japanese long-term DAPT cohort.
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.
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Shimamatsu et al. (2019) conducted an RCT in Coronary heart disease on long-term dual antiplatelet therapy after percutaneous coronary intervention (n=96). Prasugrel vs. Clopidogrel 75 mg daily was evaluated on Rate of patients who achieved PRU < 208 at the end of 12 weeks of treatment (p=0.024). Switching from clopidogrel to prasugrel significantly increased the rate of patients achieving optimal platelet reactivity (PRU < 208) to 90.0% compared to 36.4% with continued clopidogrel.
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