Korean Circ J.  2022 Apr;52(4):304-319. 10.4070/kcj.2021.0293.

Prasugrel-based De-Escalation of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With STEMI

• Ki YJ
• Lee BK
• Park KW
• Bae JW
• Hwang D
• Kang J
• Han JK
• Yang HM
• Kang HJ
• Koo BK
• Kim DB
• Chae IH
• Moon KW
• Park HW
• Won KB
• Jeon DW
• Han KR
• Choi SW
• Ryu JK
• Jeong MH
• Cha KS
• Kim HS
• on behalf of the HOST-RP-ACS investigators

• KMID: 2528025
• DOI: http://doi.org/10.4070/kcj.2021.0293

Abstract

Background and Objectives
De-escalation of dual-antiplatelet therapy through dose reduction of prasugrel improved net adverse clinical events (NACEs) after acute coronary syndrome (ACS), mainly through the reduction of bleeding without an increase in ischemic outcomes. Whether the benefits of de-escalation are sustained in highly thrombotic conditions such as ST-elevation myocardial infarction (STEMI) is unknown. We aimed to assess the efficacy and safety of de-escalation therapy in patients with STEMI or non-STsegment elevation ACS (NSTE-ACS).
Methods
This is a pre-specified subgroup analysis of the HOST-REDUCE-POLYTECH-ACS trial. ACS patients were randomized to prasugrel de-escalation (5 mg daily) or conventional dose (10 mg daily) at 1-month post-percutaneous coronary intervention. The primary endpoint was a NACE, defined as a composite of all-cause death, non-fatal myocardial infarction, stent thrombosis, clinically driven revascularization, stroke, and bleeding events of grade ≥2 Bleeding Academic Research Consortium (BARC) criteria at 1 year.
Results
Among 2,338 patients included in the randomization, 326 patients were diagnosed with STEMI. In patients with NSTE-ACS, the risk of the primary endpoint was significantly reduced with de-escalation (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48– 0.89; p=0.006 for de-escalation vs. conventional), mainly driven by a reduced bleeding. However, in those with STEMI, there was no difference in the occurrence of the primary outcome (HR, 1.04; 95% CI, 0.48–2.26; p=0.915; p for interaction=0.271).
Conclusions
Prasugrel dose de-escalation reduced the rate of NACE and bleeding, without increasing the rate of ischemic events in NSTE-ACS patients but not in STEMI patients.

Keyword

Acute coronary syndrome; Percutaneous coronary intervention; Prasugrel; ST elevation myocardial infarction; Non-ST elevated myocardial infarction

Figure

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  Figure 1 Study flow chart.NSTE-ACS = non-ST-segment elevation acute coronary syndrome; RP-ACS = REDUCE-POLYTECH-ACS; STEMI = ST-elevation myocardial infarction.

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  Figure 2 Primary endpoint in the intention-to-treat population at 1-year follow-up: (A) primary endpoint, (B) efficacy outcomes (cardiac death, myocardial infarction, stent thrombosis, and ischemic stroke), and (C) safety outcomes (BARC ≥2 bleeding events).CI = confidence interval; HR = hazard ratio; NSTE-ACS = non-ST-segment elevation acute coronary syndrome; STEMI = ST-elevation myocardial infarction.

• 

  Figure 3 Prespecified landmark analysis at 4 weeks after index procedure: (A) primary endpoint, (B) efficacy outcomes (cardiac death, myocardial infarction, stent thrombosis, and ischemic stroke), and (C) safety outcomes (BARC ≥2 bleeding events).CI = confidence interval; HR = hazard ratio; NSTE-ACS = non-ST-segment elevation acute coronary syndrome; STEMI = ST-elevation myocardial infarction.*Model fitted by penalized maximum likelihood.

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