Background: Data on drug-coated balloon (DCB) treatment in the context of diabetes mellitus (DM) and multivessel coronary artery disease (CAD) are limited. We aimed to investigate the clinical impact of DCB-based revascularization on percutaneous coronary intervention (PCI) in patients with DM and multivessel CAD. Methods: A total of 254 patients with multivessel disease (104 patients with DM) successfully treated with DCB alone or combined with drug-eluting stent (DES) were retrospectively enrolled (DCB-based group) and compared with 254 propensity-matched patients treated with second-generation DES from the PTRG-DES registry (n = 13,160 patients) (DES-only group). Major adverse cardiovascular events (MACE) comprised cardiac death, myocardial infarction, stroke, stent or target lesion thrombosis, target vessel revascularization, and major bleeding at 2 years. Results: The DCB-based group was associated with a reduced risk of MACE in patients with DM (hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.05–0.68, p = 0.003], but not in those without DM (HR 0.52, 95% CI 0.20–1.38, p = 0.167) at the 2-year follow-up. In patients with DM, the risk of cardiac death was lower in the DCB-based group than the DES-only group, but not in those without DM. In both patients with or without DM, the burdens of DES and small DES (less than 2.5 mm) used were lower in the DCB-based group than in the DES-only group. Conclusions: In multivessel CAD, the clinical benefit of a DCB-based revascularization strategy appears to be more evident in patients with DM than in those without DM after 2 years of follow-up. (Impact of Drug-Coated Balloon Treatment in De Novo Coronary Lesion; NCT04619277)
Keywords: Diabetes mellitus; Multivessel; Drug-coated balloon; Drug-eluting stent; Coronary artery disease; Percutaneous coronary intervention
Patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) have worse clinical outcomes, such as increased risk of in-stent restenosis (ISR), stent thrombosis, myocardial infarction, and death, compared with that of patients without DM [[
Drug-coated balloon (DCB) treatment leaves nothing of lesions behind, and it reduces the risk of stent-associated maladaptive biologic responses causative of restenosis and thrombosis, and allows for favorable natural vascular healing [[
A total of 254 patients with successful PCI for multivessel CAD including patients with DM who received DCB alone or in combination with DES were retrospectively enrolled between 2012 and 2020 from three teaching hospitals in South Korea (Ulsan University Hospital, Ulsan Medical Center, and Korea University Ansan Hospital) with experienced physicians providing treatment for patients with multivessel CAD using DCB (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; NCT04619277). Eligible patients were those who had lesions with ≥ 50% narrowing and who the investigator considered to require PCI for two or more major epicardial coronary lesions. Patients with DM were defined as patients with a history of DM under medication or fasting plasma glucose ≥ 126 mg/dL. All patients were diagnosed with Type 2 DM in this study. Patients were excluded from the analysis if they had previously undergone CABG; presented with cardiogenic shock, thrombolysis before PCI, single-vessel disease, or suboptimal or failed PCI for target lesions; or were lost to follow-up. Additionally, patients' vessels were required to be sufficiently large to accommodate DES implantation. The results of the hybrid approach in these patients were compared with those of 254 propensity-matched patients from the PTRG-DES consortium, who were treated with DES-only (https://
The study protocol was approved by the institutional review board of each participating center, and all patients provided written informed consent at the time of enrollment.
For patients with multivessel disease, the PCI target lesions were first determined, then balloon angioplasty was performed to determine whether DCB treatment would be possible. The DCB-based treatment group received interventions performed according to international and Asia-Pacific consensus recommendations for DCB treatment [[
All 508 patients underwent a clinical follow-up following the index procedure via telephone interviews and outpatient clinic visits. The study endpoint was cumulative major adverse cardiac events (MACE) at 2 years, a composite of cardiac death, myocardial infarction (MI), stroke, probable or definite stent or target lesion thrombosis, target vessel revascularization (TVR), and major bleeding. Cardiac death was defined as any death that was not clearly of extracardiac origin, including MI, according to previously published guidelines [[
Clinical characteristics are reported as percentages for categorical variables and as means with standard deviations for continuous variables. Comparisons between groups were made using either Pearson's chi-squared test or Fisher's exact test for categorical variables, and Student's t-test for continuous variables, as appropriate. In comparing clinical outcomes between the groups, the cumulative incidences of MACE and other outcomes were estimated using the Kaplan–Meier method, and the curves were compared using the log-rank test. To reduce the effect of potential confounding factors, we used propensity score matching to adjust for differences in baseline characteristics. The propensity score was estimated using logistic regression by considering demographic and clinical variables (age, sex, hypertension, DM, current smoking, end-stage renal disease, previous history of MI, previous history of PCI, left main disease, presentation of acute MI, chronic total occlusion, total number of treated vessels, total number of devices used, total length of devices used, and mean diameter of devices used). Without setting the caliper size (R default caliper size = NULL), patients were 1:1 matched using the nearest-neighbor method with respect to the calculated score. All p-values were two-sided, and a value of < 0.05 was considered statistically significant. R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria) was used for all statistical analyses in this study.
Among a total of 508 patients with multivessel disease, 219 patients (43.1%) composed the DM group, and 289 patients (56.9%) composed the non-DM group. DCB-based treatment was performed in 47.5% (n = 104) of the DM group and 51.9% (n = 150) of the non-DM group. The baseline clinical and procedural characteristics of the patients are described by DM group and treatment strategy in Table 1. In the DM group, those receiving DCB-based compared to DES-only treatment had lower total number of DES used (n = 0.9 for DCB-based vs. n = 2.5 for DES-only; p < 0.001), shorter total length of DES (21.5 mm for DCB-based vs. 64.9 mm for DES-only; p < 0.001), larger mean diameter of DES (3.2 mm for DCB-based vs. 2.8 mm for DES-only; p < 0.001), and less use of small DES (≤ 2.5 mm) (10.1% for DCB-based vs. 42.6% for DES-only; p < 0.001). In the non-DM group, those receiving DCB-based compared to DES-only treatment showed less presentation of stable angina (25.3% for DCB-based vs. 38.1% for DES-only; p = 0.027), lower total number of DES used (n = 1.0 for DCB-based vs. n = 2.6 for DES-only; p < 0.001), shorter total length of DES (24.4 mm for DCB-based vs. 63.6 mm for DES-only; p < 0.001), larger mean diameter of DES (3.3 mm for DCB-based vs. 2.8 mm for DES-only; p < 0.001), and less use of small DES (≤ 2.5 mm) (6.1% for DCB-based vs. 43.2% for DES-only; p < 0.001). Of patients in the DM group receiving DCB-based treatment, 33.7% were treated with DCB alone and 66.3% were treated with the hybrid approach combining DCB and DES, while of those in the non-DM group who received DCB-based treatment, 34.7% were treated with DCB alone and 65.3% were treated with the hybrid approach. For those receiving DCB-based treatment, the number of stents used was significantly reduced (by 66.5% and 62.6% in the DM and non-DM groups, respectively [Fig. 1A]) compared to those receiving the DES-only treatment.
Table 1 Clinical and procedural characteristics of the patients according to DM and treatment strategy
DM (n = 219) Non-DM (n = 289) DCB-based treatment DES-only treatment p Value DCB-based treatment DES-only treatment p Value (n = 104) (n = 115) (n = 150) (n = 139) Age, years 64.3 ±9.2 64.4 ±10.8 0.926 62.1 ±10.6 63.7 ±11.1 0.219 Men 75 (72.1) 73 (63.5) 0.223 111 (74.0) 96 (69.1) 0.424 Hypertension 84 (80.8) 96 (83.5) 0.729 97 (64.7) 94 (67.6) 0.684 Smoking 36 (34.6) 33 (28.7) 0.426 51 (34.0) 49 (35.3) 0.921 Prior MI 8 (7.7) 12 (10.4) 0.639 17 (11.3) 19 (13.7) 0.673 Prior PCI 13 (12.5) 21 (18.3) 0.323 25 (16.7) 19 (13.7) 0.586 End-stage renal disease 9 (8.7) 12 (10.4) 0.828 3 (2.0) 4 (2.9) 0.919 Clinical presentation Stable angina 34 (32.7) 44 (38.3) 0.473 38 (25.3) 53 (38.1) Unstable angina 47 (45.2) 37 (32.2) 0.066 64 (42.7) 45 (32.4) 0.093 Acute myocardial infarction 23 (22.1) 34 (29.6) 0.271 48 (32.0) 41 (29.5) 0.739 DCB-only treatment 35 (33.7) 0 - 52 (34.7) 0 - Target lesion and procedure characteristics Left main 11 (10.6) 17 (14.8) 0.467 21 (14.0) 23 (16.5) 0.661 LAD 83 (79.8) 89 (77.4) 0.787 111 (74.0) 109 (78.4) 0.458 LCX 80 (76.9) 69 (60.0) 119 (79.3) 94 (67.6) RCA 54 (51.9) 80 (69.6) 82 (54.7) 83 (59.7) 0.455 Chronic total occlusion 20 (19.2) 26 (22.6) 0.655 32 (21.3) 22 (15.8) 0.294 Total number of diseased vessel 2.4 ± 0.5 2.4 ± 0.5 0.447 2.4 ± 0.5 2.4 ± 0.5 0.876 Total number of treated vessel 2.2 ± 0.4 2.2 ± 0.4 0.987 2.2 ± 0.4 2.2 ± 0.4 0.356 Total number of device used 2.6 ± 0.8 2.5 ± 0.9 0.744 2.6 ± 1.0 2.6 ± 0.9 0.727 Total device length, mm 66.1 ± 23.8 64.9 ± 30.6 0.741 64.6 ± 26.6 63.6 ± 29.9 0.760 Device diameter, mm 2.8 ± 0.2 2.8 ± 0.4 0.222 2.8 ± 0.3 2.8 ± 0.4 0.613 Total number of DCB used 1.7 ± 0.8 0 1.6 ± 0.8 0 Total DCB length, mm 44.5 ± 23.9 0 40.2 ± 23.4 0 DCB diameter, mm 2.6 ± 0.2 0 2.6 ± 0.3 0 Small DCB used (diameter ≦ 2.5 mm) 64/104 (61.5) 0 96/150 (64.0) 0 Total number of DES used 0.9 ± 0.8 2.5 ± 0.9 1.0 ± 0.9 2.6 ± 0.9 Total DES length, mm 21.5 ± 20.7 64.9 ± 30.6 24.4 ± 24.7 63.6 ± 29.9 DES diameter, mm 3.2 ± 0.5 2.8 ± 0.4 3.3 ± 0.5 2.8 ± 0.4 Small DES used (≦ 2.5 mm) 7/69 (10.1) 49/115 (42.6) 6/98 (6.1) 60/139 (43.2)
Values are presented as the mean ± SD or n (%) DM = diabetes mellitus; DCB = drug-coated balloon; DES = drug-eluting stent; MI = myocardial infarction; PCI = percutaneous coronary intervention; LAD = left anterior descending artery; LCX = left circumflex artery; RCA = right coronary artery
Table 2 shows the comparison of the cumulative incidences of major clinical outcomes between groups for the 2-year follow-up period (interquartile range [IQR]: 1.1–4.5 years). In the DM group, those receiving DCB-based treatment had both a significantly lower cumulative incidence of MACE at 2 years than those in the DES-only treatment (n = 3 [2.9%] for DCB-based vs. n = 16 [13.9%] for DES-only; hazard ratio [HR]: 0.19; 95% confidence interval [CI]: 0.05–0.68; log-rank p = 0.003) (Table 2; Fig. 2A, and Fig. 1B) and a significantly lower incidence of cardiac death compared to those receiving DES-only treatment (n = 0 for DCB-based vs. n = 4 [3.5%] for DES-only; log-rank p = 0.044) (Table 2; Fig. 2B). However, in the non-DM group, the cumulative incidences of MACE and cardiac death did not significantly differ for those receiving DCB-based compared to DES-only treatment (MACE: n = 7 [4.7%] for DCB-based vs. n = 12 [8.6%] for DES-only [HR: 0.52; 95% CI: 0.20–1.38; log-rank p = 0.167]; cardiac death: n = 1 [0.7%] for DCB-based vs. n = 2 [1.4%] for DES-only [HR: 0.43; 95% CI: 0.03–5.34; log-rank p = 0.481]) (Table 2; Fig. 2C and D, and Fig. 1B). There were no cases of MI or target lesion thrombosis in patients receiving DCB-based treatment in either the DM or the non-DM group.
Table 2 Comparison of clinical outcomes between DCB-based treatment and DES-only treatment according to the presence of DM at 2 years follow-up
DM (n = 219) Non-DM (n = 289) DCB-based treatment DES-only treatment HR (95% CI) p Value* DCB-based treatment DES-only treatment HR (95% CI) p Value* (n = 104) (n = 115) (n = 150) (n = 139) MACE 3 (2.9) 16 (13.9) 0.19 (0.05–0.68) 7 (4.7) 12 (8.6) 0.52 (0.20–1.38) 0.167 Cardiac death 0 4 (3.5) - 1 (0.7) 2 (1.4) 0.43 (0.03–5.34) 0.481 Myocardial infarction 0 1 (0.9) - 0.290 0 2 (1.4) - 0.155 Stroke 0 1 (0.9) - 0.333 0 0 - - Stent or target lesion thrombosis 0 0 - - 0 1 (0.7) - 0.316 Target vessel revascularization 2 (1.9) 8 (7.0) 0.27 (0.05–1.34) 0.077 6 (4.0) 8 (5.8) 0.69 (0.23–2.07) 0.492 Major bleeding 1 (1.0) 4 (3.5) 0.26 (0.03–2.34) 0.196 0 3 (2.2) - 0.063
Values are presented as n (%). p value* was obtained from the log-rank test MACE was composed of cardiac death, myocardial infarction, stroke, stent or target lesion thrombosis, target vessel revascularization, and major bleeding (Bleeding Academic Research Consortium bleeding type 3 or greater) DM = diabetes mellitus; DCB = drug-coated balloon; DES = drug-eluting stent; MACE = major adverse cardiovascular events
Graph: Fig. 2Cumulative incidence of MACE and cardiac death after DCB-based and DES-only revascularization in the DM group (A, B) and the non-DM group (C, D)
Graph: Fig. 1Clinical impact of DCB-based PCI in patients with DM and multivessel CADA. Proportions of DCB and DES devices used in the DM and non-DM groupsB. Cumulative incidence of MACE during 2 years of follow-up by treatment strategy and the presence of DM
The main findings of this study were as follows: (
DM accelerates atherosclerosis in multiple vascular beds and is associated with a significantly higher risk of CAD, and its prevalence is still growing globally [[
The current guidelines suggest that for patients with DM and multivessel CAD, revascularization with CABG might be the preferred approach [[
The advantages of DCB treatment include homogeneous drug delivery to the vessel wall, immediate drug release without the use of a polymer, and the freedom of leaving no foreign object behind in the vessel. The DCB treatment, involving no-metallic stent struts or polymer, may reduce intimal hyperplasia and vessel inflammation, preserving vessel anatomy and flow compared with DES. Furthermore, although the exact mechanism of late lumen increase is not well understood, DCB treatment of de novo coronary lesions after predilation was known to lead to late lumen enlargement. Therefore, considering the nature of DM in CAD, a DCB-based strategy (DCB alone or combined with DES) may be a good alternative to a DES-only strategy in treating multivessel CAD in patients with DM.
In the present study, we showed that in patient with DM who had multivessel CAD, DCB-based treatment was significantly associated with a lower risk of MACE and cardiac death than DES-only treatment; however, this association was not seen in patients without DM. Although it showed no statistical significance, we demonstrated that the need for TVR in the DM group was numerically lower with DCB-based treatment compared with DES-only treatment (1.9% vs. 7.0%; aHR: 0.23; 95% CI: 0.03–1.46; log-rank p = 0.077). Our study results are consistent with those of previous studies on the long-term clinical impact regarding TVR of DCB versus DES treatment in patients with DM having de novo coronary lesions [[
Patients with DM have a relatively smaller vessel caliber, with longer and more diffuse de novo lesions, compared to patients who do not have DM [[
There are some limitations in this study. First, this study has the innate limitations of its observational nature and the use of registry data. Laboratory test results such as glycosylated hemoglobin A1c (HbA1c) during the follow-up period, which may be associated with DM management status and could impact the outcome, but we could not provide these data. In addition, leaving the choice of treatment strategy to the discretion of the physician inevitably introduces the limitation of selection bias. We addressed this issue by applying extensive sensitivity analyses in which measured or unmeasured confounders were adjusted to minimize the bias from different baseline characteristics. Second, each patient enrolled in this study was treated at an expert center in DCB-only treatment for de novo CAD. Thus, these results may not be reproducible without an adequate learning curve. Third, differences between the enrollment periods of the two groups might have led to differences in results related to technological changes. However, although the PTRG-DES registry was established in 2003, the patients whose data were used in the propensity match analysis had received second-generation DES. Therefore, differences between groups related to device development and PCI technique improvement are not expected to be significant. Further prospective randomized non-inferiority or superiority clinical trials with larger numbers of patients are needed to evaluate long-term outcomes after DCB-based treatment in patients with DM and multivessel CAD.
In multivessel CAD, a DCB-based treatment approach (DCB alone or combined with DES) was associated with a reduced risk of MACE in patients with DM, but not in patients without DM. The role of DCB in this setting should be assessed in prospective randomized controlled trials.
None.
Her AY, Shin ES and Kim S performed study, and Her AY, Shin ES and Kim B had statistical analysis. Her AY and Shin ES wrote manuscript. Her AY, Shin ES, Kim TH, Sohn CB, Choi BJ, Park Y, Cho JR and Jeong YH designed study and contributed discussion and revised manuscript. Her AY and Shin ES edited manuscript.
This study has been worked with the support of a research grant of Kangwon National University in 2023.
Not applicable.
The study protocol was approved by the institutional review board of each participating center, and all patients provided written informed consent at the time of enrollment.
Not applicable.
All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
• DM
- Diabetes mellitus
• PCI
- Percutaneous coronary intervention
• ISR
- In-stent restenosis
• CABG
- Coronary artery bypass graft
• DES
- Drug-eluting stent
• CAD
- Coronary artery disease
• DCB
- Drug-coated balloon
• TIMI
- Thrombolysis in myocardial infarction
• MACE
- Major adverse cardiovascular events
• TVR
- Target vessel revascularization
• MI
- Myocardial infarction
• POCO
- Patient-oriented composite outcome
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By Ae-Young Her; Eun-Seok Shin; Sunwon Kim; Bitna Kim; Tae-Hyun Kim; Chang-Bae Sohn; Byung Joo Choi; Yongwhi Park; Jung Rae Cho and Young-Hoon Jeong
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