Efficacy and safety of prasugrel monotherapy compared with clopidogrel in Japanese patients with acute coronary syndrome after percutaneous coronary intervention
E Nawata, S Honda, K Murai, K Mitsui, T Iwai, K Sawada, H Matama, M Fujino, S Yoneda, K Takagi, K Nakao, Y Kataoka, Y Asaumi, T NoguchiAbstract
Introduction
The optimal P2Y12 inhibitor for long-term single antiplatelet therapy (SAPT) after acute coronary syndrome (ACS) remains uncertain. Evidence directly comparing the long-term efficacy and safety of prasugrel and clopidogrel as SAPT after percutaneous coronary intervention (PCI) remains limited.
Purpose
To compare the efficacy and safety of clopidogrel versus prasugrel monotherapy in patients with ACS after PCI.
Methods
This single-center observational study included consecutive ACS patients who underwent PCI between January 2019 and December 2021 (N=963). Follow-up was initiated only after both 6 months had elapsed since PCI and patients had transitioned to SAPT. Patients received clopidogrel 75 mg once daily or adjusted-dose prasugrel 3.75 mg once daily as monotherapy. The primary endpoint was net adverse clinical events (NACE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, non-fatal cerebral infarction, stent thrombosis, and clinically relevant bleeding (BARC type 2, 3 and 5). The secondary endpoint was major adverse cardiovascular events (MACE), defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal cerebral infarction.
Results
A total of 283 patients were included in the final analysis, with 160 receiving clopidogrel and 123 receiving prasugrel (Figure 1). Compared with the prasugrel group, patients receiving clopidogrel were older, more frequently female, and had lower body weight. Furthermore, the proportion of patients meeting the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria was higher in the clopidogrel monotherapy group. NACE occurred in 21.3% of patients in the clopidogrel group and 8.9% in the prasugrel group (P =0.005). MACE occurred in 17.5% and 4.9%, respectively (P=0.001) (Table 1). Kaplan–Meier analysis demonstrated a significantly higher cumulative incidence of NACE in the clopidogrel group compared with the prasugrel group (log-rank P=0.036; Figure 2A). Similarly, MACE was also more frequent in the clopidogrel group (log-rank P=0.024; Figure 2B). In multivariable analysis, clopidogrel monotherapy (OR 2.17, 95% CI 1.04–4.82; P=0.039) and ARC-defined high bleeding risk (OR 2.65, 95% CI 1.19–6.16; P=0.017) were independently associated with NACE (Table 2).
Conclusion
Among stabilized ACS patients in whom follow-up began at the later of 6 months after PCI and transition to SAPT, adjusted-dose prasugrel monotherapy was associated with lower ischemic and net adverse clinical events compared with clopidogrel monotherapy. Large-scale randomized controlled trials are warranted to confirm these findings.Picture 1Picture 2