Cardiovasc Diabetol. 2023;22(1):245.

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

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제1저자 전기현 · 교신저자 서정원

PMID 37679760 PMC10486029 DOI 10.1186/s12933-023-01976-4 IF 15.6 순환기내과

소속 (15)

Department of Internal Medicine, Department of Cardiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
CAU Thrombosis and Biomarker Center, Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Seoul, South Korea.
Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
Division of Cardiology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Internal Medicine, Cardiovascular Center, Gyeongsang National University School of Medicine, Gyeongsang National University Changwon Hospital, Changwon, South Korea.
Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Department of Cardiology, Yonsei University Wonju Severance Christian Hospital, Wonju, South Korea.
Division of Cardiology, Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, South Korea.
Cardiology Division, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea.
Division of Cardiology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea.
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea.
Department of Cardiology, Dong-A University Hospital, Busan, South Korea.
Division of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
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 mellitusHemoglobin A1cInsulinPlatelet reactivityStenting

Figures

**Fig. 1** Distribution of PRU according to DM status DM: diabetes mellitus; PRU: P2Y12 reaction unit

**Fig. 2** Kaplan–Meier curves of MACCE and major bleeding rate according to diabetic condition. A 5-year MACCE with and without DM; B 5-year MACCE according to index Hb A1c; C 5-year major bleeding with and without DM; D 5-year major bleeding according to index Hb A1c Hb A1c: hemoglobin A1c; MACCE: major cardiac and cerebrovascular event

**Fig. 3** Relative hazard ratio for MACCE according to PRU level by restricted cubic spline curve. A all patients; B non-diabetic patients; C diabetic patients MACCE: major cardiac and cerebrovascular event; PRU: P2Y12 reaction unit

**Fig. 4** Kaplan–Meier curves according to presence of DM and HPR phenotype. A MACCE; B all-cause death; C major bleeding DM: diabetes mellitus; HPR: high platelet reactivity; HR: hazard ratio; MACCE: major cardiac and cerebrovascular event

그림 출처: PubMed Central 공개 논문 (PMC10486029)

Conflict of interest statement

Dr. Jeong has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals, as well as research grants or support from Yuhan Pharmaceuticals and U&I Corporation. Dr. Song has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, Bayer Korea, and Samjin Pharmaceutical. Dr. Joo has received honoraria for lectures from AstraZeneca, Hanmi, Samjin, Dong-A, HK inno. N Pharmaceuticals, and DIO Medical Ltd. The other authors have no potential conflicts of interest to disclose.

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