Prasugrel switching from clopidogrel after percutaneous coronary intervention for acute coronary syndrome in Taiwanese patients: an analysis of safety and efficacy

Abstract

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.

Keywords: Acute coronary syndrome; Antiplatelet; P2Y12 reaction unit; Prasugrel; Regimen switch.

Conflict of interest statement

Shuji Tsukiyama, Wei-Chen Yang, and Li-Chung Cheng are Daiichi-Sankyo employees. Virginia Rafael and Christian Nikolajsen are Linical employees and participated in a project sponsored by Daiichi Sankyo. Wen-Lieng Lee was a chair of a meeting sponsored by Daiichi Sankyo.

© 2021. The Author(s).

Figures

Fig. 1

Patient enrollment flowchart for Switch Study (NCT03672097) showing the flow of patients enrolled from the start of the study to end of Period 1 and Period 2. The number of patients and the reasons for patients not available for analysis are indicated. 1m 1 month, PFT platelet function testing

Fig. 2

Comparisons of PRU values at baseline and Week 4 in all patients and prespecified patient subgroups. a PRU values at baseline and Week 4 by total patients and subgroups of ACS type and sex. b Change in PRU values from baseline by total patients and subgroups of ACS type and sex; p values of each PRU change are shown next to the corresponding data point. Each bar shows the mean PRU or change with SD (solid line) and 95% CI (dashed line). c Histograms of P2Y12 reaction unit (PRU) at baseline and Week 4. The dashed lines indicate the PRU levels evaluated in the study. ACS acute coronary syndrome, CI confidence interval, NSTEMI non-STEMI, PRU P2YP12 reaction unit, SD standard deviation, STEMI ST elevation myocardial infarction, UA unstable angina

Fig. 3

Risk factor analyses for PRU change from baseline and HPR (PRU > 208) at Week 4. a The adjusted LS means with 95% CI and the corresponding p values of factors associated with PRU change from baseline are shown; statistical analysis performed by a stepwise ANCOVA model. b The adjusted OR with 95% CI and the corresponding p values of factors associated with HPR (PRU > 208) at Week 4 are shown; statistical analysis performed by a multivariate logistic model. ANCOVA analysis of covariance, BMI body mass index, CI confidence interval, LS least squares, OR odds ratio, PRU P2YP12 reaction unit, SD standard deviation