Implication of diabetic status on platelet reactivity and clinical outcomes after drug-eluting stent implantation: results from the PTRG-DES consortium

Ki-Hyun Jeon; Young-Hoon Jeong; In-Ho Chae; Byeong-Keuk Kim; Hyung Joon Joo; Kiyuk Chang; Yongwhi Park; Young Bin Song; Sung Gyun Ahn; Sang Yeub Lee; Jung Rae Cho; Ae-Young Her; Hyo-Soo Kim; Moo Hyun Kim; Do-Sun Lim; Eun-Seok Shin; Jung-Won Suh; PTRG-DES Consortium Investigators

doi:10.1186/s12933-023-01976-4

Implication of diabetic status on platelet reactivity and clinical outcomes after drug-eluting stent implantation: results from the PTRG-DES consortium

Cardiovasc Diabetol. 2023 Sep 7;22(1):245. doi: 10.1186/s12933-023-01976-4.

Authors

Ki-Hyun Jeon¹, Young-Hoon Jeong², In-Ho Chae¹, Byeong-Keuk Kim³, Hyung Joon Joo⁴, Kiyuk Chang⁵, Yongwhi Park⁶, Young Bin Song⁷, Sung Gyun Ahn⁸, Sang Yeub Lee⁹, Jung Rae Cho¹⁰, Ae-Young Her¹¹, Hyo-Soo Kim¹², Moo Hyun Kim¹³, Do-Sun Lim⁴, Eun-Seok Shin¹⁴, Jung-Won Suh¹⁵; PTRG-DES Consortium Investigators

Affiliations

¹ Department of Internal Medicine, Department of Cardiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
² CAU Thrombosis and Biomarker Center, Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Seoul, South Korea.
³ Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea.
⁴ Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
⁵ Division of Cardiology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
⁶ Department of Internal Medicine, Cardiovascular Center, Gyeongsang National University School of Medicine, Gyeongsang National University Changwon Hospital, Changwon, South Korea.
⁷ Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁸ Department of Cardiology, Yonsei University Wonju Severance Christian Hospital, Wonju, South Korea.
⁹ Division of Cardiology, Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, South Korea.
¹⁰ Cardiology Division, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea.
¹¹ Division of Cardiology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea.
¹² Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea.
¹³ Department of Cardiology, Dong-A University Hospital, Busan, South Korea.
¹⁴ Division of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
¹⁵ Department of Internal Medicine, Department of Cardiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea. suhjw1@gmail.com.

Abstract

Background: Diabetes mellitus (DM) is associated with thrombogenicity, clinically manifested with atherothrombotic events after percutaneous cutaneous intervention (PCI). This study aimed to investigate association between DM status and platelet reactivity, and their prognostic implication in PCI-treated patients.

Methods: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test (PTRG-PFT) cohort was established to determine the linkage of platelet function test (PFT) with long-term prognosis during dual antiplatelet therapy including clopidogrel in patients treated with drug-eluting stent (DES). We assessed platelet reactivity using VerifyNow and 'high platelet reactivity (HPR)' was defined as ≥ 252 P2Y12 reaction unit (PRU). Major adverse cardiac and cerebrovascular event (MACCE) was a composite of all-cause death, myocardial infarction, stent thrombosis or stroke.

Results: Between July 2003 and Aug 2018, DES-treated patients with available PFT were enrolled (n = 11,714). Diabetic patients demonstrated significant higher levels of platelet reactivity (DM vs. non-DM: 225.7 ± 77.5 vs. 213.6 ± 79.1 PRU, P < 0.001) and greater prevalence of HPR compared to non-diabetic patients (38.1% vs. 32.0%, P < 0.001). PRU level and prevalence of HPR were significantly associated with insulin requirement and Hb_A1c level, as well as diabetic status. DM status and HPR phenotype had a similar prognostic implication, which showed the synergistic clinical impact on MACCE. Association between PRU level and MACCE occurrence seemed higher in diabetic vs. non-diabetic patients. In non-DM patients, HPR phenotype did not significantly increase the risk of MACCE (adjusted hazard ratio [HR_adj]: 1.073; 95% confidence interval [CI]: 0.869-1.325; P = 0.511), whereas HPR was an independent determinant for MACCE occurrence among diabetic patients (HR_adj: 1.507; 95% CI: 1.193-1.902; P < 0.001).

Conclusion: The levels of on-clopidogrel platelet reactivity are determined by diabetic status and the severity of DM. In addition, HPR phenotype significantly increases the risk of MACCE only in diabetic patients.

Clinical trial registration: URL: https://www.

Clinicaltrials: gov . Unique identifier: NCT04734028.

Keywords: Diabetes mellitus; Hemoglobin A1c; Insulin; Platelet reactivity; Stenting.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood Platelets
Clopidogrel / adverse effects
Diabetes Mellitus* / diagnosis
Diabetes Mellitus* / epidemiology
Drug-Eluting Stents*
Humans
Percutaneous Coronary Intervention* / adverse effects

Substances

Clopidogrel

Associated data

ClinicalTrials.gov/NCT04734028