Kyu-Sun Lee ¹, Keun-Ho Park ², Kyung Woo Park ¹, Seung-Woon Rha ², Doyeon Hwang ¹, Jeehoon Kang ¹, Jung-Kyu Han ¹, Han-Mo Yang ¹, Hyun-Jae Kang ¹, Bon-Kwon Koo ¹, Nam-Ho Lee ³, Jay Young Rhew ⁴, Kook Jin Chun ⁵, Young-Hyo Lim ⁶, Jung Min Bong ⁷, Jang-Whan Bae ⁸, Bong Ki Lee ⁹, Seok-Yeon Kim ¹⁰, Won-Yong Shin ¹¹, Hong-Seok Lim ¹², Kyungil Park ¹³, Hyo-Soo Kim ¹

¹Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Republic of Korea.
²Korea University Guro Hospital, Seoul, Republic of Korea.
³Kangnam Sacred Heart Hospital, Seoul, Republic of Korea.
⁴Presbyterian medical center, Jeonju, Republic of Korea.
⁵Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
⁶Hanyang University Hospital, Seoul, Republic of Korea.
⁷Hallym General Hospital, Incheon, Republic of Korea.
⁸Chungbuk National University, Cheongju, Republic of Korea.
⁹Kangwon National University, Chuncheon, Republic of Korea.
¹⁰Seoul Medical Center, Seoul, Republic of Korea.
¹¹Soonchunyang University Cheonan Hospital, Cheonan, Republic of Korea.
¹²Ajou University Medical Center, Suwon, Republic of Korea.
¹³Dong-A University Hospital, Busan, Republic of Korea.

Drs. Lee and Park contributed equally to this work.
Corresponding authors: Kyung Woo Park, Seung-Woon Rha

Aims: The aim of this study was to evaluate the efficacy and safety of prasugrel-dose de-escalation therapy in patients with diabetes mellitus (DM)-acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).

Methods and results: This was a post-hoc analysis of the HOST-REDUCE-POLYTECH-ACS randomized trial. The efficacy and safety of prasugrel dose de-escalation therapy (prasugrel 5 mg daily) were compared with conventional therapy (prasugrel 10 mg daily) in patients with DM. The primary endpoint was net adverse clinical events (NACE), defined as a composite of all-cause death, nonfatal myocardial infarction (MI), stent thrombosis (ST), clinically driven revascularization, stroke, and BARC class ≥ 2 bleeding events. The secondary ischemic outcome was major adverse cardiovascular and cerebrovascular events (MACE), defined as the composite of cardiac death, nonfatal MI, ST, or ischemic stroke. Of 2 338 patients randomized, 990 had DM. The primary endpoint of NACE occurred in 38 patients (7.6%) receiving prasugrel dose de-escalation and in 53 patients (11.3%) receiving conventional therapy among patients with DM (HR 0.66; 95% CI 0.43-0.99; P = 0.049). Prasugrel dose de-escalation as compared with conventional therapy did not increase the risk of ischemic events (HR 1.03; 95% CI 0.56-1.88; P = 0.927) but decreased BARC class ≥ 2 bleeding in patients with DM (HR 0.44; 95% CI 0.23-0.84; P = 0.012).

Conclusion: Prasugrel dose de-escalation compared with conventional therapy may reduce the risk of net clinical outcomes, mostly driven by a reduction in bleeding without an increase in ischemic events in patients with DM.