Journal of Interventional Cardiology
Volume 2020 (2020), Article ID 1710439, 11 pages
https://doi.org/10.1155/2020/1710439

Research Article

Comparison of First- and Second-Generation Drug-Eluting Stents in Patients with Acute Myocardial Infarction and Prediabetes Based on the Hemoglobin A1c Level

Yong Hoon Kim,¹ Ae-Young Her,¹ Myung Ho Jeong,² Byeong-Keuk Kim,³ Sung-Jin Hong,³ Seunghwan Kim,⁴ Chul-Min Ahn,³ Jung-Sun Kim,³ Young-Guk Ko,³ Donghoon Choi,³ Myeong-Ki Hong,³ and Yangsoo Jang³

¹Division of Cardiology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Republic of Korea
²Department of Cardiology, Chonnam National University Hospital, Gwangju, Republic of Korea
³Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seuol, Republic of Korea
⁴Division of Cardiology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea

Correspondence should be addressed to Yong Hoon Kim; yhkim02@kangwon.ac.kr

Received 19 December 2019; Revised 27 February 2020; Accepted 20 June 2020; Published 18 July 2020

Academic Editor: Andrea Rubboli

Copyright © 2020 Yong Hoon Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Objective. To compare major clinical outcomes after successful percutaneous coronary intervention (PCI) with first-generation (1G) drug-eluting stents (DES) and second-generation (2G) DES in patients with acute myocardial infarction (AMI) and prediabetes. Background. Patients with prediabetes are associated with an increased incidence of coronary artery disease. The relative superiority of 1G- and 2G-DES in these patients is not well established. Methods. A total of 4997 patients with AMI and prediabetes were divided into two groups: the 1D-DES group (n = 726) and the 2G-DES group (n = 4271). The primary outcomes were the patient-oriented composite outcomes (POCOs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any disease revascularization at 2-year follow-up. The secondary outcome was probable or definite stent thrombosis (ST). Results. After propensity score-matching (PSM) analysis, two PSM groups (698 pairs, n = 1396, C-statistics = 0.725) were generated. The cumulative incidence rates of POCOs (hazard ratio (HR): 1.467; 95% confidence interval (CI): 1.068–2.015; ), any disease revascularization (HR: 2.259; 95% CI: 1.397–3.654; ), and ST (HR: 4.361; 95% CI: 1.243–15.30; ) in the 1G-DES group were significantly higher than those in the 2G-DES group. However, the cumulative incidence rates of all-cause death, cardiac death, and Re-MI were similar between the two groups. Conclusions. In patients with AMI and prediabetes, 2G-DES implantation was more efficacious than 1G-DES implantation over a 2-year follow-up period. However, further studies are needed to confirm these results.

1. Introduction

In the fibrinolytic era, hyperglycemia, rather than normoglycemia, was a major independent prognostic factor of adverse clinical outcomes in patients with acute myocardial infarction (AMI) [1, 2]. Similarly, in the drug-eluting stent (DES) era, hyperglycemia is an independent predictor of early and late mortality in patients with ST-segment elevation myocardial infarction (STEMI) regardless of the presence or absence of known diabetes [3, 4]. The exact mechanisms by which hyperglycemia is associated with adverse major clinical outcomes in AMI have not been fully elucidated yet. With regard to diabetes mellitus (DM), many studies have shown its association with higher long-term risk of death, myocardial infarction (MI), and repeat revascularization in patients undergoing percutaneous coronary intervention (PCI) [5–7]. Patients with prediabetes are at an increased risk of cardiovascular disease (CVD), and prediabetes is associated with an increased incidence of coronary artery disease (CAD) [8, 9]. Even though the relative superiority between the first-generation (1G) and second-generation (2G) DESs in patients with AMI is controversial [10–12], most previous studies were not performed under the circumstance of prediabetes. Therefore, the comparative long-term clinical outcomes between the two DES generations were limited. Hence, we investigated and compared the major clinical outcomes after successful PCI with 1G-DES and 2G-DES in patients with AMI and prediabetes over a 2-year follow-up period.

2. Methods

2.1. Study Population

This study was a nonrandomized, multicenter, observational, and retrospective cohort study. A total of 45863 patients from the Korea AMI Registry (KAMIR) who had AMI and underwent successful stent implantation between November 2005 and June 2015 were evaluated. KAMIR is the first nationwide and multicenter registry that included >50 community and teaching hospitals in South Korea since November 2005 [13]. Eligible patients were aged ≥18 years at the time of hospital admission. Among the patients, those with incomplete laboratory results, including unidentified blood hemoglobin (Hb) A1c and blood glucose test results (n = 27737, 60.5%), those who were lost to follow-up (n = 3275, 7.1%), those who received a bare-metal stent (n = 297, 0.6%), those with concomitant use of 1G-DES and 2G-DES (n = 174, 0.4%), those with normoglycemia (n = 3845, 8.4%), those with DM (n = 5291, 11.5%), and those with cardiogenic shock (n = 247, 0.5%) were excluded. Finally, 4997 patients with AMI and prediabetes who underwent successful DES implantation were included in the study. The patients were divided into two groups: the 1G-DES group (n = 726, 14.5%; sirolimus-eluting stent (SES; Cypher, Cordis Corp., Miami Lakes, Florida; n = 313, 43.1%) and paclitaxel-eluting stent (PES, Taxus, Boston Scientific, Natick, Massachusetts; n = 413, 56.9%)) and the 2G-DES group (n = 4271, 85.5%; zotarolimus-eluting stent (ZES; Resolute Integrity, Medtronic, Inc., Minneapolis, MN; n = 1466, 34.3%), everolimus-eluting stent (EES; Xience Prime, Abbott Vascular, Santa Clara, CA; or Promus Element, Boston Scientific, Natick, MA; n = 2132, 49.9%), biolimus-eluting stent (BES; BioMatrix Flex, Biosensors International, Morges, Switzerland; or Nobori, Terumo Corporation, Tokyo, Japan; n = 577, 13.5%), and other stents (n = 96, 2.2%); Figure 1). The study protocol was approved by the institutional review board of each participating center, and the study was conducted in accordance with the principles of the 1975 Declaration of Helsinki. In this retrospective study, we evaluated patients who had provided written informed consent prior to participation in the KAMIR study. Therefore, any information concerning adverse events of these 4997 participants with AMI and prediabetes including the time intervals and the types of events after the index PCI, which occurred during a 2-year follow-up period, was monitored at the outpatient clinic, by phone calls, or by reviewing their charts at each participating center in those days.

Figure 1: Study flowchart. AMI: acute myocardial infarction; KAMIR: Korea AMI Registry; HbA1c: hemoglobin A1c; BMS: bare-metal stent; 1G: first-generation; 2G: second-generation; DES: drug-eluting stent; PSM: propensity score-matching analysis.

2.2. Percutaneous Coronary Intervention and Medical Treatment

Coronary angiography and PCI were performed in accordance with the general guideline [14]. Before PCI, all the patients received loading doses of aspirin 200–300 mg and clopidogrel 300–600 mg; alternatively, ticagrelor 180 mg or prasugrel 60 mg was administered. Dual antiplatelet therapy (DAPT; a combination of aspirin 100 mg/day with clopidogrel 75 mg/day or ticagrelor 90 mg twice daily or prasugrel 5–10 mg/day) for > 12 months was recommended for patients who underwent PCI. Administration of triple antiplatelet therapy (cilostazol (Pletal®, Otsuka Pharmaceutical Co., Tokyo, Japan) 100 mg twice daily added to DAPT) was left to the discretion of the individual physicians.

2.3. Study Definitions and Clinical Outcomes

Prediabetes was determined based on the medical history and glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels at the index hospitalization and defined as an HbA1c level of 5.7%–6.4% and an FPG level of 100–125 mg/dL (5.6–6.9 mmol/L) [15]. ST-segment elevation myocardial infarction (STEMI) and non-STEMI were defined in accordance with the current guidelines [16, 17]. In NSTEMI cases, an early invasive treatment strategy was defined as performing PCI within 24 hours after admission [17]. A successful PCI was defined as a residual stenosis of <30% and thrombolysis in myocardial infarction (TIMI) with grade III flow for the infarct-related artery (IRA) after the procedure. The primary clinical outcome of this study was the occurrence of patient-oriented composite outcomes (POCOs) defined as all-cause death, recurrent myocardial infarction (Re-MI), or any disease revascularization (ADR) at 2-year follow-up. The secondary outcome was definite or probable stent thrombosis (ST) at 2-year follow-up. All-cause death was classified as cardiac death (CD) or non-CD. ADR was composed of target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR. The definitions of Re-MI, TLR, TVR, and non-TVR were previously published [18]. The cumulative incidence of ST was defined by current consensus as acute (0 to 24 h), subacute (24 h to 30 days), late (30 days to 1 year), and very late (>1 year) [19].

2.4. Statistical Analyses

For continuous variables, in this study, the normality test was performed using the Kolmogorov–Smirnov normality test. According to the normality results, the independent samples t-test was applied to examine the difference of continuous variables means of the two groups, and the data were expressed as the mean ± standard deviations. For categorical variables, the differences between the two groups were analyzed using the chi-squared test or, if not applicable, Fisher’s exact test, and the data were expressed as counts and percentages. To adjust for potential confounders, a propensity score-matching (PSM) analysis was performed using a logistic regression model. We tested all available variables listed in Table 1 that could be of potential relevance. The C-statistics for PSM was 0.725 in the current study. Patients in the 1G-DES group were then one-to-one matched to those in the 2G-DES group according to propensity scores with the nearest available pair-matching method. Subjects were matched with a caliper width equal to 0.01. The procedure yielded 698 matched pairs. Various clinical outcomes were estimated using the Kaplan–Meier method, and differences between the two groups were compared using the log-rank test. For all analyses, two-sided values of were considered statistically significant. All statistical analyses were performed using the SPSS version 20 software (IBM; Armonk, NY, USA).

Table 1: Baseline clinical, laboratory, and procedural characteristics.

Variables
All patients
Propensity score-matched patients

1G-DES (n = 726)
2G-DES (n = 4271)
value
1G-DES (n = 698)
2G-DES (n = 698)
value

Age (years)
63.8 ± 12.1
64.2 ± 12.4
0.464
63.9 ± 12.0
63.7 ± 12.8
0.814

Men, n (%)
535 (73.7)
3169 (74.2)
0.773
516 (73.9)
520 (74.5)
0.854

LVEF (%)
52.6 ± 12.4
52.4 ± 11.2
0.798
52.7 ± 12.54
52.4 ± 11.5
0.618

BMI (kg/m²)
24.1 ± 3.1
24.1 ± 3.3
0.854
24.1 ± 2.9
24.1 ± 3.1
0.927

SBP (mmHg)
133.7 ± 24.8
132.3 ± 25.2
0.150
133.2 ± 24.2
134.1 ± 25.5
0.502

DBP (mmHg)
82.0 ± 14.5
80.1 ± 15.0
0.003
81.5 ± 13.9
81.6 ± 15.7
0.866

STEMI, n (%)
405 (55.8)
2442 (57.2)
0.484
391 (56.0)
394 (56.4)
0.871

    Primary PCI, n (%)
376/405 (92.8)
2346/2442 (96.1)
0.003
363/391 (92.8)
371/394 (94.2)
0.452

NSTEMI, n (%)
321 (44.2)
1829 (42.8)
0.484
307 (44.0)
304 (43.6)
0.871

    PCI within 24 hours
246/321 (76.6)
1563/1829 (85.5)
<0.001
239/307 (77.9)
239/304 (78.6)
0.818

CPR on admission
17 (2.3)
181 (4.2)
0.013
17 (2.4)
16 (2.3)
0.860

Hypertension, n (%)
362 (49.9)
2087 (48.9)
0.619
351(50.3)
346 (49.6)
0.789

Dyslipidemia, n (%)
70 (9.6)
503 (11.8)
0.095
70 (10.0)
72 (10.3)
0.859

Previous MI, n (%)
20 (2.8)
131 (3.1)
0.649
19 (2.7)
15 (2.1)
0.603

Previous PCI, n (%)
41 (5.6)
228 (5.3)
0.733
40 (5.7)
33 (4.7)
0.471

Previous CABG, n (%)
3 (0.4)
13 (0.3)
0.631
3 (0.4)
2 (0.3)
0.654

Previous CVA, n (%)
45 (6.2)
253 (5.9)
0.773
43 (6.2)
37 (5.3)
0.565

Previous HF, n (%)
8 (1.1)
48 (1.1)
0.959
8 (1.1)
5 (0.7)
0.579

Current smokers, n (%)
293 (40.4)
1875 (43.98)
0.075
280 (40.1)
307 (44.0)
0.143

Peak CK-MB (mg/dL)
127.8 ± 208.2
136.4 ± 196.5
0.278
129.4 ± 210.2
119.5 ± 141.6
0.301

Peak troponin-I (ng/mL)
39.3 ± 88.9
46.1 ± 120.4
0.178
40.4 ± 83.0
39.7 ± 59.3
0.869

NT-proBNP (pg/mL)
2141.2 ± 5100.7
1852.1 ± 4784.8
0.232
2044.5 ± 4062.4
1997.2 ± 3788.8
0.821

hs-CRP (mg/dL)
12.9 ± 36.8
9.7 ± 53.4
0.145
12.1 ± 31.3
14.1 ± 85.9
0.550

Serum creatinine (mg/L)
1.11 ± 1.03
1.10 ± 1.52
0.935
1.11 ± 1.03
1.22 ± 2.77
0.314

Serum glucose (mg/dL)
149.3 ± 48.9
150.4 ± 50.8
0.590
149.1 ± 47.6
151.4 ± 49.9
0.381

Total cholesterol (mg/dL)
188.1 ± 43.4
186.9 ± 44.4
0.494
187.9 ± 43.3
185.8 ± 42.0
0.360

Triglyceride (mg/L)
117.9 ± 75.6
131.9 ± 102.2
<0.001
118.8 ± 75.7
120.3 ± 67.1
0.698

HDL cholesterol (mg/L)
45.0 ± 12.8
43.6 ± 15.4
0.020
44.8 ± 12.3
44.1 ± 15.4
0.380

LDL cholesterol (mg/L)
121.0 ± 36.7
119.5 ± 43.3
0.361
120.7 ± 38.6
118.7 ± 36.1
0.300

Discharge medications

    Aspirin, n (%)
684 (94.2)
4119 (96.4)
0.004
658 (94.3)
654 (93.7)
0.653

    Clopidogel, n (%)
707 (97.4)
3674 (86.0)
<0.001
680 (97.4)
680 (97.4)
1.000

    Ticagrelor, n (%)
3 (0.4)
363 (8.5)
<0.001
3 (0.4)
4 (0.6)
0.705

    Prasugrel, n (%)
2 (0.3)
194 (4.5)
<0.001
2 (0.3)
2 (0.3)
1.000

    Cilostazol, n (%)
217 (29.9)
812 (19.0)
<0.001
197 (28.2)
213 (30.5)
0.378

    BB, n (%)
573 (78.9)
3552 (83.2)
0.005
552 (79.1)
571 (81.8)
0.200

    ACEI, n (%)
419 (57.7)
2311 (54.1)
0.071
396 (56.7)
393 (56.3)
0.871

    ARB, n (%)
178 (24.5)
1101 (25.8)
0.472
174 (24.9)
171 (24.5)
0.901

    CCB, n (%)
54 (7.4)
240 (5.6)
0.054
48 (6.9)
50 (7.2)
0.917

    Lipid-lowering agents, n (%)
535 (73.7)
3673 (86.0)
<0.001
530 (75.9)
542 (77.7)
0.447

Infarct-related artery

    Left main, n (%)
18 (2.5)
77 (1.8)
0.217
14 (2.0)
168 (2.3)
0.712

    LAD, n (%)
363 (50.0)
2147 (50.3)
0.878
349 (50.0)
340 (48.7)
0.630

    LCx, n (%)
134 (18.5)
706 (16.5)
0.199
130 (18.6)
128 (18.3)
0.890

    RCA, n (%)
211 (29.1)
1341 (31.4)
0.209
204 (29.2)
213 (30.5)
0.590

Treated vessel

    Left main, n (%)
25 (3.4)
127 (3.0)
0.495
21 (3.0)
24 (3.4)
0.649

    LAD, n (%)
443 (61.0)
2537 (59.4)
0.411
424 (60.7)
434 (62.2)
0.582

    LCx, n (%)
207 (28.5)
1106 (25.9)
0.139
197 (28.2)
191 (27.4)
0.720

    RCA, n (%)
262 (36.1)
1624 (38.0)
0.320
255 (36.5)
265 (38.0)
0.580

ACC/AHA lesion type

    Type B1, n (%)
113 (15.6)
580 (13.6)
0.153
110 (15.8)
115 (16.5)
0.716

    Type B2, n (%)
237 (32.6)
1367 (32.0)
0.734
226 (32.4)
231 (33.1)
0.776

    Type C, n (%)
266 (36.6)
1877 (43.9)
<0.001
262 (37.5)
248 (35.5)
0.436

Extent of CAD

    1-vessel, n (%)
321 (44.2)
2165 (50.7)
<0.001
303 (43.4)
296 (42.4)
0.705

    2-vessel, n (%)
224 (30.9)
1326 (31.0)
0.917
217 (31.1)
242 (34.7)
0.154

    ≥3-vessel, n (%)
181 (24.9)
780 (18.3)
<0.001
171 (24.5)
160 (22.9)
0.489

IVUS
177 (24.4)
1007 (23.6)
0.638
172 (24.6)
159 (22.8)
0.413

OCT
0 (0.0)
33 (0.8)
0.017
0 (0.0)
0 (0.0)
—

FFR
1 (0.1)
59 (1.4)
0.004
1 (0.1)
0 (0.0)
0.317

Stents

    SES, n (%)
313 (43.1)

303 (43.4)

    PES, n (%)
413 (56.9)

395 (56.6)

    ZES, n (%)

1466 (34.3)

237 (34.0)

    EES, n (%)

2132 (49.9)

366 (52.4)

    BES, n (%)

577 (13.5)

73 (10.5)

    Others, n (%)

96 (2.2)

22 (3.1)

Stent diameter (mm)
3.13 ± 0.42
3.13 ± 0.42
0.987
3.13 ± 0.41
3.14 ± 0.43
0.592

Stent length (mm)
25.9 ± 7.15
26.9 ± 11.5
0.031
25.9 ± 7.06
25.9 ± 10.0
0.907

Number of stents
1.54 ± 0.84
1.48 ± 0.80
0.051
1.54 ± 0.80
1.55 ± 0.84
0.740

Values are means ± SD or numbers and percentages. The values for categorical data were obtained from the chi-square or Fisher’s exact test. For continuous variables, differences between the two groups were evaluated with independent samples t-test. LVEF: left ventricular ejection fraction; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; STEMI: ST-segment elevation myocardial infarction; NSTEMI: non-ST-segment elevation myocardial infarction; PCI: percutaneous coronary intervention; CPR: cardiopulmonary resuscitation; CABG: coronary artery bypass graft; CVA: cerebrovascular events; HF: heart failure; CK-MB: creatine kinase myocardial band; NT-proBNP: N-terminal pro-brain natriuretic peptide; hs-CRP: high-sensitivity C-reactive protein; HDL: high-density lipoprotein; LDL: low-density lipoprotein; BB: beta-blocker; ACEI: angiotensin-converting enzyme inhibitors; ARB: angiotensin receptor blocker; CCB: calcium channel blockers; LAD: left anterior descending coronary artery; LCx: left circumflex coronary artery; RCA: right coronary artery; ACC/AHA: American College of Cardiology/American Heart Association; CAD: coronary artery disease; IVUS: intravascular ultrasound; OCT: optical coherence tomography; FFR: fractional flow reserve; SES: sirolimus-eluting stent; PES: paclitaxel-eluting stent; ZES: zotarolimus-eluting stent; EES: everolimus-eluting stent; BES: biolimus-eluting stent.

3. Results

3.1. Baseline Characteristics

The baseline clinical, laboratory, and procedural characteristics of the study population are summarized in Table 1. The mean age (63.8 ± 12.1 years vs. 64.2 ± 12.4 years, ) and proportion of men (73.7% vs. 74.2%, ) of the enrolled patients were similar between the two groups. The mean left ventricular ejection fraction (LVEF) was not significantly different between the two groups (52.6% ± 12.4% vs. 52.4% ± 11.2%, ) and was >50% in both groups. However, the proportion of patients who underwent primary PCI (92.8% vs. 96.1%, ) or PCI within 24 hours (76.6% vs. 85.5%, ) was significantly higher in the 2G-DES group than in the 1G-DES group. The proportion of patients with cardiopulmonary resuscitation (CPR) on admission (4.2% vs. 2.3%, ) and the prescription rates of aspirin, ticagrelor, prasugrel, and lipid-lowering agents as discharge medications; the number of American College of Cardiology/American Heart Association (ACC/AHA) type C lesions; the incidence of single-vessel disease; the use frequency of optical coherence tomography and fractional flow reserve; and the mean total length of the deployed stents were significantly greater in the 2G-DES group than in the 1G-DES group. By contrast, the prescription rates of clopidogrel and cilostazol as discharge medications and the incidence of ≥ 3-vessel disease were significantly higher in the 1G-DES group than in the 2G-DES group. However, these intergroup differences in baseline characteristics were well balanced after PSM adjustment.

3.2. Clinical Outcomes

The cumulative incidences of major clinical outcomes at 2 years are listed in Table 2 and Figure 2. After PSM analysis, the cumulative incidence rates of POCOs (hazard ratio (HR): 1.467; 95% confidence interval (CI): 1.068–2.015; ), ADR (HR: 2.259; 95% CI: 1.397–3.654; ), and ST (HR: 4.361; 95% CI: 1.243–15.30; ) were significantly higher in the 1G-DES group than in the 2G-DES group. However, the cumulative incidence rates of all-cause death, CD, and Re-MI were similar between the two groups. Table 3 shows the independent predictors of POCOs and ADR at 2 years. Old age (≥65 years), LVEF of <50%, CPR on admission, use of a lipid-lowering agent, and multivessel disease were significant independent predictors of POCOs. In addition, multivessel disease was a significant independent predictor of ADR in this study.

Table 2: Clinical outcomes by Kaplan–Meier analysis and Cox proportional hazard ratio analysis at 2 years.

Outcomes
1G-DES
2G-DES
Log-rank
Hazard ratio (95% CI)
value

All patients

POCOs
100 (13.9)
353 (8.8)
<0.001
1.616 (1.294–2.017)
<0.001

    All-cause death
43 (5.9)
171 (4.2)
0.035
1.431 (1.024–1.999)
0.036

        Cardiac death
34 (4.7)
129 (3.1)
0.030
1.514 (1.037–2.209)
0.032

    Re-MI
9 (1.3)
79 (2.0)
0.192
1.576 (0.791–3.141)
0.196

    Death or MI
52 (7.2)
244 (6.0)
0.224
1.204 (0.892–1.624)
0.225

    aAny disease revascularization
58 (8.4)
138 (3.6)
<0.001
2.383 (1.752–3.238)
<0.001

Stent thrombosis (probable or definite)
14 (1.9)
28 (0.7)
0.001
2.956 (1.556–5.615)
0.001

    Acute
1 (0.1)
2 (0.0)
0.355
2.941 (0.267–32.44)
0.378

    Subacute
4 (0.6)
13 (0.3)
0.290
1.814 (0.591–5.563)
0.298

    Late
7 (1.0)
10 (0.2)
0.002
4.146 (1.578–10.89)
0.004

    Very late
2 (0.3)
3 (0.1)
0.103
3.967 (0.663–23.74)
0.131

Propensity score-matched patients

POCOs
94 (13.5)
64 (9.5)
0.017
1.467 (1.068–2.015)
0.018

    All-cause death
42 (6.0)
36 (5.3)
0.541
1.149 (0.736–1.793)
0.541

        Cardiac death
33 (4.8)
25 (3.7)
0.317
1.303 (0.775–2.191)
0.319

    Re-MI
8 (1.2)
8 (1.2)
0.971
1.019 (0.382–2.714)
0.971

    Death or MI
50 (7.2)
44 (6.5)
0.588
1.118 (0.746–1.677)
0.588

    aAny disease revascularization
54 (8.2)
24 (3.7)
0.001
2.259 (1.397–3.654)
0.001

Stent thrombosis (probable or definite)
13 (1.9)
3 (0.4)
0.012
4.361 (1.243–15.30)
0.021

    Acute
1 (0.1)
0 (0.0)
0.317
—
—

    Subacute
3 (0.4)
1 (0.1)
0.316
3.006 (0.313–28.90)
0.340

    Late
7 (1.0)
2 (0.3)
0.093
3.526 (0.733–16.98)
0.116

    Very late
2 (0.3)
0 (0.0)
0.155
—
—

1G: first-generation; 2G: second-generation; DES: drug-eluting stent; HR: hazard ratio; CI: confidence interval; POCOs: patient-oriented composite outcomes; Re-MI: recurrent myocardial infarction. aAny disease revascularization was composed of target lesion revascularization, target vessel revascularization, and nontarget vessel revascularization.

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)

(j)

(k)

(l)

Figure 2: Kaplan–Meier analysis of the incidence rates of POCOs (a, b), all-cause death (c, d), cardiac death (e, f), Re-MI (g, h), any disease revascularization (i, j), and ST (k, l) in all patients (a, c, e, g, i, k) and PSM patients (b, d, f, h, j, l) at 2 years. 1G: first-generation; 2G: second-generation; DES: drug-eluting stent; HR: hazard ratio; CI: confidence interval; POCOs: patient-oriented composite outcomes; Re-MI: recurrent myocardial infarction; ST: stent thrombosis; PSM: propensity score-matching analysis.

Table 3: Independent predictors for POCOs and any disease revascularization at 2 years in all patients.

Variables
POCOs
Any disease revascularization

Univariate
Multivariate
Univariate
Multivariate

HR (95% CI)
value
HR (95% CI)
value
HR (95% CI)
value
HR (95% CI)
value

1G-DES vs. 2G-DES
1.616 (1.294–2.017)
<0.001
1.520 (1.213–1.905)
<0.001
2.383 (1.753–3.238)
<0.001
2.228 (1.631–3.043)
<0.001

Age (≥65 years)
1.548 (1.282–1.867)
<0.001
1.318 (1.072–1.620)
0.009
1.024 (0.774–1.355)
0.866
1.109 (0.812–1.515)
0.517

Men
1.269 (1.039–1.550)
0.020
1.030 (0.828–1.282)
0.789
1.097 (0.802–1.501
0.563
1.072 (0.759–1.515)
0.692

LVEF (<50%)
1.652 (1.374–1.986)
<0.001
1.437 (1.191–1.733)
<0.001
1.037 (0.777–1.383)
0.807
1.027 (0.767–1.375)
0.859

Hypertension
1.333 (1.107–1.605)
0.002
1.187 (0.977–1.441)
0.084
1.249 (0.943–1.654)
0.121
1.168 (0.870–1.568)
0.302

Dyslipidemia
1.075 (0.811–1.425)
0.617
1.182 (0.887–1.575)
0.252
1.240 (0.826–1.862)
0.299
1.206 (0.798–1.825)
0.374

CPR on admission
4.004 (3.020–5.309)
<0.001
3.722 (2.799–4.950)
<0.001
1.625 (0.860–3.071)
0.135
1.659 (0.875–3.142)
0.121

Lipid-lowering agent
2.487 (2.038–3.035)
<0.001
2.355 (1.908–2.857)
<0.001
1.503 (1.069–2.114)
0.019
1.514 (1.073–2.137)
0.118

MVD
1.733 (1.430–2.102)
<0.001
1.585 (1.303–1.928)
<0.001
1.852 (1.377–2.491)
<0.001
1.793 (1.328–2.420)
<0.001

ACC/AHA type B2/C lesion
1.141 (0.918–1.419)
0.234
1.131 (0.905–1.413)
0.278
1.014 (0.738–1.392)
0.933
1.062 (0.768–1.469)
0.715

Stent diameter (<3.0 mm)
1.176 (0.967–1.431)
0.104
1.088 (0.891–1.328)
0.407
1.097 (0.812–1.482)
0.548
1.031 (0.760–1.400)
0.843

Stent length (≥28 mm)
1.174 (0.975–1.413)
0.091
1.060 (0.877–1.281)
0.546
1.380 (1.043–1.826)
0.024
1.332 (1.000–1.774)
0.050

POCOs: patient-oriented composite outcomes; HR: hazard ratio; CI, confidence interval; 1G: first-generation; 2G: second-generation; DES: drug-eluting stent; LVEF: left ventricular ejection fraction; CPR: cardiopulmonary resuscitation; MVD: multivessel disease; ACC/AHA: American College of Cardiology/American Heart Association.

4. Discussion

The main findings of this study are as follows: (1) the cumulative incidence rates of POCOs, ADR, and ST were significantly higher in the 1G-DES group than in the 2G-DES group; (2) the cumulative incidence rates of all-cause death, CD, and Re-MI were similar between the two groups; (3) Multivessel disease was a common independent predictor of both POCOs and ADR.

1G-DES is made of stainless steel with a closed-cell design and has a relatively thick inner diameter (130–150 μm), making them difficult to maneuver through significantly diseased and calcified vessels. In addition, the major serious problem of the 1G-DES was the occurrence of (very) late ST, induced by the polymer or even by the stent material itself [20]. By contrast, the 2G-DES is made of cobalt-chromium (CoCr) and has thinner stent struts (50–90 μm) and showed improved ability for deliverability while maintaining an adequate radial strength [21]. The polymers in the 2G-DES were more biocompatible and thromboresistant than those in the 1G-DES [22] One meta-analysis revealed that CoCr-EESs were associated with significantly lower rates of definite ST than PESs (odds ratio (OR): 0.34, 95% CI: 0.19–0.62) [23]. With regard to diabetes, Bavishi et al. [24] performed a meta-analysis of randomized trials to compare the efficacy and safety between the 1G-DES and the 2G-DES. In their study, the EES showed significantly decreased incidence rates of major adverse cardiac events by 18% (relative risk (RR)): 0.82, 95% CI: 0.70–0.96) and ST by 46% (RR: 0.54, 95% CI: 0.35–0.82) as compared with the 1G-DES. Moreover, the EES showed a trend toward reduced incidence rates of TLR and TVR (). The ZES was associated with 89% increased risk of TLR (RR: 1.89, 95% CI: 1.10–3.22) as compared with the 1G-DES in their study. The results of our study may be similar to those of their study. However, their study population was not confined to patients with AMI.

Higher blood glucose level was an important factor of increased risk of death and poor clinical outcome after AMI [25–27]. Kowalczyk et al. [28] reported that patients with HbA1c levels of ≤5.9% had significantly lower posthospital mortality (4.5%) than those with HbA1c levels of >5.9% (25.0%; ) in 2146 AMI survivors. However, the evident underlying pathological mechanisms related to the adverse clinical outcomes in hyperglycemia status remain unclear. Liu et al. [29] suggested that elevated glucose level is associated with the development of endothelial dysfunction. Moreover, this endothelial dysfunction is the leading cause of platelet activation [30]. In addition, hyperglycemia plays an important role in the development of diabetic macrovascular complications, including atherosclerosis and restenosis [31]. Patients with diabetes have more diffuse disease that often rapidly progresses and tend to have exaggerated neointimal hyperplasia and increased need for repeat revascularization [32]. Moreover, glycosylation of vascular collagen and elastin is thought to lead to a more diffuse pattern of restenosis [33].

Even though the 2G-DES uses an evolved stent platform and a more biocompatible polymer than that in the 1G-DES, data concerning the outcomes between the two DESs in patients with AMI are conflicting [10, 34]. With regard to diabetes, the relative superiority between the 1G-DES and the 2G-DES in patients with diabetes is controversial [35–37]. Furthermore, in patients with prediabetes, limited follow-up data are available regarding the comparative long-term effects of 1G-DES and 2G-DES implantation. Even though the study population, follow-up duration, and definition of prediabetes were different between in our study and that of Kok et al. [38], clinical outcomes were compared between prediabetes and diabetes (11.1% vs. 10.5%). Therefore, the major clinical outcomes of our study could reflect the meta-analysis results of the study of Bavishi et al. [24].

ST is another controversial issue in the DES era. In our study, unexpectedly, the cumulative incidence of very late ST was similar between the two DES generations. By contrast, late ST was significantly different between the two groups. The main cause of these results may be related to the relatively higher numbers of patients who received EES (n = 2132/4271, 49.9% ) in this study population. In the study of Bangalore et al. [39], EES was associated with the lowest incidence rates of TVR, Re-MI, and ST as compared with ZES and PES. In the study of Kedhi et al. [35], the difference in the risk of ST was already observed in the early phase and was maintained during the 1-year follow-up. Similarly, in our study, the risk of ST was already determined within 1 year after the index PCI.

Although oral glucose tolerance test (OGTT) is considered more sensitive than measurement of HbA1c level for defining diabetes [15], in this study, prediabetes was determined on the basis of patients’ medical history and HbA1c and FPG levels at the index hospitalization. One of the main advantages of measuring HbA1c level is that it can be performed at any time because it does not require fasting. This is especially convenient in circumstances in which performing the test and interpreting the result may be difficult in the milieu of an acute illness such as AMI [38, 40]. Therefore, despite that measurement of HbA1c level may not be ideal, it can be used as an alternative diagnostic tool for making these important assessments.

In this KAMIR study, >50 high-volume university or community hospitals in South Korea participated, but the study population was insufficient to provide meaningful results. Taken together, the results of this study may provide a meaningful message to the interventional cardiologist during PCI to help select the appropriate DES, especially in patients with AMI and prediabetes.

This study has several limitations. First, some data may have been underreported and/or missing owing to the nonrandomized nature of this study. Second, a proportion of the patients with prediabetes (based on HbA1c level) may be diagnosed with overt diabetes if retested using a more sensitive diagnostic test (e.g., OGTT). This may be a source of bias in the study. Third, the study was based on discharge medications, as we could not confirm the participants’ adherence or nonadherence to their antidiabetic drugs. Therefore, we could not discern the degree of glycemic control of the participants during the follow-up period, which might constitute an additional bias in this study. Fourth, the 2-year follow-up period was relatively short for determining the long-term major clinical outcomes; thus, longer follow-up period data are required. Fifth, we performed a PSM analysis to strengthen our results, but variables not included in the KAMIR study may have affected the study outcomes.

In conclusion, with regard to the beneficial effects on POCOs, ADR, and ST reduction capacity, in patient with AMI and prediabetes, 2G-DES implantation was more efficacious than 1G-DES implantation during the 2-year follow-up period. However, further randomized trials are needed to more precisely confirm the superior efficacy of 2G-DES over 1G-DES.

Data Availability

The data used to support the findings of this study are included within the article and supplementary tables.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Authors’ Contributions

Yong Hoon Kim and Ae-Young Her contributed equally to this work.

Acknowledgments

The authors thank all of the clinical investigators who contributed time and effort to this study, as well as the Korea Acute Myocardial Infarction (KAMIR) Investigators. This research was supported by a fund (2016-ER6304-02) by Research of Korea Centers for Disease Control and Prevention.

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