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

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.

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