Daiichi Sankyo Taiwan Ltd.

A significant proportion of acute coronary syndrome (ACS) patients experience high on-treatment platelet reactivity (HPR) on clopidogrel-based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).

This study assessed key independent risk factors associated with significant HPR risk on clopidogrel, but not prasugrel, in the Switch Study cohort of 200 Taiwanese ACS patients who switched from clopidogrel to low-dose prasugrel for maintenance DAPT after PCI.

Univariate analysis and stepwise multivariate logistic regression analysis were conducted to identify key independent risk factors for HPR on clopidogrel, but not prasugrel.

A HANC [H: low hemoglobin (< 13 g/dL for men and < 12 g/dL for women); A: age ≥ 65 years; N: non-ST elevation myocardial infarction; C: chronic kidney disease as defined by estimated glomerular filtration rate < 60 mL/min] risk stratification score was developed, and demonstrated optimal sensitivity and specificity at a cutoff score of ≥ 2. The HANC score compared favorably against the recently validated ABCD score in the full Switch Study cohort (n = 200), and the ABCD-GENE score in a genotyped cohort (n = 102).

The HANC score may serve to alert clinicians to patients at potentially higher HPR risk on clopidogrel, but not prasugrel. Further research to validate this score and assess its correlation with clinical outcomes is warranted.

The recommended maintenance dose of prasugrel for East Asian populations (i.e., Japanese and Taiwanese) is 3.75 mg as part of dual antiplatelet therapy (DAPT) for the prevention of recurrent ischemia and stent thrombosis in acute coronary syndrome (ACS). This modified dosage regimen has been established in studies conducted in Japan; however, the efficacy and safety of switching from clopidogrel to prasugrel DAPT among Taiwanese patients remain to be explored. In this phase IV, multicenter, single-arm, open-label study, we evaluated the 4-week pharmacodynamic response, and the 48-week safety outcomes of prasugrel 3.75 mg after a switch from clopidogrel in Taiwanese ACS patients. A total of 203 prasugrel-naïve ACS patients (over 90% male) who had received post-PCI clopidogrel DAPT for at least 2 weeks were enrolled from ten medical centers in Taiwan and subsequently switched to prasugrel 3.75 mg DAPT. Four weeks after the switch, P2Y12 reaction unit (PRU) values were significantly decreased in the total cohort (mean − 18.2 ± 48.1; 95% confidence interval − 24.9 to − 11.5,p < 0.001), and there was an overall consistent antiplatelet response in the treated subjects. The proportion of patients with high on-treatment platelet reactivity (HPR; PRU > 208) dropped from 23.5 to 10% (p < 0.001). Female sex was associated with a greater PRU reduction with prasugrel, whereas HPR at baseline, age ≥ 65 years, and body mass index ≥ 25 best predicted HPR at Week 4. Throughout the 48-week treatment with prasugrel, the incidences of MACE (1.0%) and TIMI major bleeding (2.0%) were rather low, accompanying an acceptable safety profile of TIMI minor (6.4%) and non-major, non-minor clinically relevant bleeding (3.0%). Overall, switching to the maintenance dose of prasugrel (3.75 mg) was observed to be effective and well tolerated among post-PCI ACS patients in Taiwan. Clinical Trial Registration Number: NCT03672097.