Long-term outcomes of prasugrel-based de-escalation versus conventional therapy after PCI in ACS patients

Background/Introduction The HOST-REDUCE-POLYTECH-ACS trial demonstrated that a prasugrel-based dose-de-escalation strategy 1 month after percutaneous coronary intervention (PCI) reduced the risk of adverse clinical outcomes for up to one year in acute coronary syndrome (ACS) patients. However, the long-term legacy effect of this strategy remains poorly studied. Purpose This study aims to evaluate the long-term benefit of a prasugrel-based dose de-escalation strategy compared with conventional strategy. Additionally, it aims to investigate the outcomes based on the choice of single antiplatelet therapy following prasugrel-based dual antiplatelet therapy (DAPT). Methods This study is a three-year follow-up study of the HOST-REDUCE-POLYTECH-ACS trial which compared the efficacy and safety of a prasugrel-based dose de-escalation strategy with a conventional strategy after PCI. The primary endpoint was net adverse clinical events (NACE) at three years, including all-cause death, non-fatal myocardial infarction, stent thrombosis, repeat revascularization, stroke, and bleeding events of grade 2 or higher according to the Bleeding Academic Research Consortium (BARC) criteria. A landmark analysis was conducted after one year from PCI. Additionally, patients were re-grouped and analyzed based on the choice of single antiplatelet therapy (SAPT) following prasugrel-based DAPT. Results A total of 2,338 ACS patients were randomized to either the prasugrel-based dose de-escalation group (1,170 patients) or conventional group (1,168 patients). The mean age was 58.8 years, and 89.2% were male. During the 3-year follow-up, the risk of NACE was significantly lower in the de-escalation group (18.0% vs 22.5%, HR 0.78, 95% CI; 0.65-0.93). However, in the landmark analysis, this benefit was not evident beyond one year (11.9% vs 14.3%, HR 0.82, 95% CI 0.65-1.04). Additionally, the benefit of prasugrel-based dose de-escalation was not significant for either ischemic (HR 0.98, 95% CI 0.75-1.30, p=0.909) or bleeding outcomes (HR 0.80, 95% CI 0.54-1.22, p=0.300). Following prasugrel-based DAPT, patients were further grouped based on their single antiplatelet use. 784 patients were assigned to the aspirin group, and 381 patients were assigned to the clopidogrel group. Landmark analysis revealed that the clopidogrel group had significantly lower ischemic events (6.0% vs 1.6%, HR 0.26, 95% CI 0.11-0.61, p=0.002) without an increase in bleeding events (2.3% vs 2.8%, HR 1.24, 95% CI 0.81-1.57, p=0.591). Conclusion The long-term benefits of a prasugrel-based dose de-escalation strategy were not evident after switching to another single antiplatelet agent. However following prasugrel, clopidogrel could be a more favorable option than aspirin as it reduced ischemic events without increasing bleeding risk.