Title: Long-term outcomes of drug-coated balloons vs. drug-eluting stents in coronary chronic total occlusion angioplasty: the SPARTAN-CTO study
Subject: Clinical Research in Cardiology, https://doi.org/10.1007/s00392-026-02852-3
Author: Rajkumar Natarajan ; Natasha Corballis ; Ioannis Merinopoulos ; Tharusha Gunawardena ; Upul Wickramarachchi ; Allan Clark ; Vassilios S. Vassiliou ; Simon C. Eccleshall ; SPARTAN-Norfolk consortium
Keywords: CTO angioplasty;DCB CTO PCI;DCB angioplasty;DES CTO PCI

Clinical Research in Cardiology

Clinical Research in Cardiology
https://doi.org/10.1007/s00392-026-02852-3
ORIGINAL PAPER
Long-term outcomes of drug-coated balloons vs. drug-eluting stents in coronary chronic total occlusion angioplasty: the SPARTAN-CTO study
Rajkumar Natarajan^1,2 · Natasha Corballis^1,2 · Ioannis Merinopoulos^1,2 · Tharusha Gunawardena^1,2 ·
Upul Wickramarachchi^1,2 · Allan Clark · Vassilios S. Vassiliou^1,2 · Simon C. Eccleshall · SPARTAN-Norfolk consortium

Norwich Medical School, University of East Anglia,
2.06 Bob Champion Research & Education Building, Norwich NR4 7TJ, UK

Department of Cardiology, Norwich University Hospital, Norfolkand, UK

Received: 25 October 2025 / Accepted: 11 January 2026
© Crown 2026
Abstract
Aim The role of drug-coated balloon (DCB)–only strategy in de novo chronic total occlusion (CTO) percutaneous coronary intervention (PCI) remains uncertain. We compared DCB with drug-eluting stent (DES) strategies in patients undergoing CTO angioplasty.
Methods We retrospectively analyzed 170 patients with de novo CTO undergoing PCI between 2013 and 2019. Patients were treated with either DCB-only (n = 85) or DES-only (n = 85) strategies. The primary endpoint was target vessel revascularization (TVR); secondary endpoints included all-cause mortality, cardiovascular death, target vessel-myocardial infarction (TV-MI), any MI, and a composite of all-cause mortality, MI, and TVR. Median follow-up was 3.67 years.
Results TVR occurred in 11 (12.9%) DCB vs. 5 (5.9%) DES patients (HR 2.33, 95% CI 0.81–6.74, p = 0.118). All-cause mortality (7.1% vs. 12.9%; HR 0.56, p = 0.262) and the composite endpoint (21.2% vs. 20.0%; HR 1.15, p = 0.686) did not differ significantly. After adjustment for creatinine, J-CTO score, and vessel diameter, outcomes remained comparable between groups. Creatinine was independently associated with mortality and the composite endpoint. No acute vessel closure or thrombosis occurred within 30 days. During follow-up, no target lesion thrombosis was observed in the DCB group, while one late stent thrombosis (1.2%) occurred in the DES group.
Conclusion In this single-center study, a DCB-only strategy for de novo CTO PCI demonstrated long-term efficacy and safety outcomes comparable to DES, supporting DCB as a potential alternative.
Vassilios S. Vassiliou and Simon C. Eccleshall contributed equally to this work.
* Rajkumar Natarajan
r.natarajan@uea.ac.uk; nrajkumar1990@gmail.com

Graphical Abstract

SPARTAN-CTO STUDY- DCB vs. DES in CTO PCI
Are long-term outcomes comparable between DCB

and DES in de novo CTO PCI?

DCB showed similar outcomes to DES in de novo CTO PCI
Keywords CTO angioplasty · DCB CTO PCI · DCB angioplasty · DES CTO PCI

Introduction
From Kaltenbach’s pioneering chronic total occlusion (CTO) angioplasties in Frankfurt in the late 1970 s to the contemporary hybrid era, the journey of CTO PCI has been remarkable [1, 2]. Early CTO attempts with balloon angioplasty achieved success rates of only 50–60% with frequent restenosis, and coronary artery bypass grafting remained the mainstay of treatment [3–7]. The subsequent stent era, beginning with bare-metal stents and later drug-eluting stents (DES), transformed CTO PCI, particularly as Japanese operators pioneered dedicated wires, microcatheters, retrograde techniques, and the Japanese-CTO (J-CTO) score [8–14]. Contemporary hybrid CTO crossing algorithms now deliver procedural success rates above 85–90% in expert centers [15–17].
CTO lesions are inherently complex, characterized by extensive diffusely diseased segments, poor landing zones, heavy calcification, and negatively remodeled vessels with impaired vasomotion [17, 18]. These factors drive an increased number of stent implantations and yet incomplete coverage, resulting in longer stent lengths, systemically undersized and malapposed due to the intricate disrupted vessel architecture and positive remodeling post-PCI [19–24]. These unfavorable conditions translate into poorer outcomes with stent failures as high as 24% [25–28].
Drug-coated balloon technology could mitigate the stent- related failures in this particular complex coronary subset, and it is now increasingly used as either a DCB-only strategy or as a hybrid strategy with DES in successful cases [29]. In failed CTO recanalization, DCB is used for its vessel healing properties after subintimal or intra-plaque modification (PM) as an investment procedure to enable distal vessel wiring in subsequent procedures [30]. However, the evidence on the use of DCB in CTO is scarce.
Our study aimed to describe the safety and long-term outcomes of DCB angioplasty in CTO patients compared to DES.
Methods
Registry and ethics
The Safety of Paclitaxel-Drug-Coated Balloon Angioplasty of Coronary Chronic Total Occlusion (SPARTAN-CTO) study is an investigator-initiated, single-center, retrospective cohort study. At the time of data collection, our center performed the highest volume of DCB-only PCI in the UK. Our PCI data are prospectively collected in a clinical database as part of the SPARTAN registry (Clinical trials government unique identifier: NCT04482972). The study was approved by the Northwest Haydock (17/NW/0278), Research Ethics Committee (REC), and the Institutional Review Board of the Norfolk and Norwich University Hospital. The Confidentiality Advisory Group (CAG) waived the requirement for patient consent due to the retrospective nature of our study (17/CAG/0145). With the approval of the REC, CAG, and local approval, we can interrogate the database using two national data storage warehouses from NHS Digital, Hospital Episode Statistics (HES), and National Institute of Cardiovascular Outcome Research (NICOR). This provided the International Classification of Diseases (ICD)-10 diagnostic codes, which were used to identify patient outcomes, ensuring that all hospital admissions, including those outside of our center, were reported.
Study population
We retrospectively analyzed consecutive patients with de novo CTO lesions treated with DCB or DES during PCI, from January 2013 until November 2019. Patients who had initial investment CTO procedure with a POBA (plain old balloon angioplasty) or had a failed recanalization and went on to successful staged CTO procedure involving definitive DES or DCB therapy were included for analysis. Patients who presented with cardiac arrest, intubation and ventilation, or in cardiogenic shock were excluded. Patients who opted out of HES data sharing for research were excluded. All patients were identified from our prospective SPARTAN registry, which was interrogated retrospectively for the purpose of this study. No matching procedure was performed; the equal group sizes reflect real-world practice rather than a matched design.
Angiographic analysis
All angiograms were reviewed by experienced operators to confirm the CTO anatomy, calculate the Japanese CTO (J-CTO) score, classify dissections, and determine the outcomes of revascularization. CTO was defined as completely occluded arteries without antegrade coronary flow with a presumed or documented duration of more than 3 months, as per CTO-ARC definition [31]. The J-CTO score was calculated to determine the complexity of the CTO, and a score of ≥ 2 was defined as a high J-CTO score [32]. Vessel diameter was estimated based on the nominal diameter of the balloon or stent sized to the reference segment at the operator’s discretion. Length of the treated segment was defined as the cumulative length of DCB or DES used to cover the target lesion. Coronary dissections were categorized according to the National Heart, Lung, and Blood Institute classification system (NHLBI types A–F). An acceptable angiographic outcome after DCB treatment was defined as TIMI 3 flow, residual stenosis ≤ 50%, and the absence of flow-limiting dissection. For DES implantation, an acceptable result was defined as TIMI 3 flow with residual stenosis ≤ 30%. A suboptimal recanalization was defined as antegrade flow of TIMI grade < 3, with residual stenosis of > 50% in the DCB group or > 30% in the DES group. Procedural techniques, including lesion preparation and device selection, were left to the operator’s discretion in accordance with standard PCI practice. All DCBs used were paclitaxel-coated devices (SeQuent Please, SeQuent Please NEO, and Falcon). The DES cohort comprised a mixture of contemporary stent platforms (Promus Premier, Resolute Onyx, Synergy, Ultimaster, Xience, Taxus, coroflex, Vision, and Combo Dual).
Study endpoints
The primary endpoint is target vessel revascularization (TVR), in line with academic research consortium recommendation (ARC-CTO). Secondary endpoints are all-cause mortality, cardiovascular death (CVD), target vessel-myocardial infarction (TV-MI), any MI, and a composite of all-cause mortality, TVR, and any MI. All definitions are as described by ARC- CTO [31]. All outcomes were adjudicated by two independent reviewers who were blinded to the intervention for mortality.
Statistical analysis
The descriptive statistics of baseline factors of the two treatment groups were compared using a two-sample t-test for continuous variables and a chi-squared test for binary or categorical variables. For the primary and secondary endpoints, the follow-up time was truncated at the time of mortality due to any cause. Cox proportional hazards models were used to estimate the hazard ratios of each endpoint alongside the relevant confidence interval and p-value. The models fitted with unadjusted and then adjusted for three pre-defined selected variables (creatinine, J-CTO score, and vessel diameter) as a fully adjusted model was inappropriate given the number of events. Model assumptions were checked using Schoenfeld residuals to assess for proportionality. For secondary endpoints with few events (less than 20), only unadjusted models were estimated. Creatinine, J-CTO score, and vessel diameter were pre-selected for inclusion in the adjusted models based on clinical relevance and established evidence in CTO PCI. Creatinine is a recognized predictor of long-term mortality, J-CTO score reflects lesion complexity and procedural difficulty, and smaller vessel diameter is associated with increased restenosis and repeat revascularization risk. Cumulative incidence curves (1-Kaplan Meier) were constructed for each endpoint.
Results
Study population
Between January 2013 and November 2019, a total of 170 patients with de novo CTO were included in the analysis,
referred to as the “de novo CTO cohort.” Of these patients, 85 underwent DCB-only strategy (DCB group) and 85 with DES-only strategy (DES group). Figure 1 represents the study population and distribution of cases.
Baseline characteristics
A total of 170 patients were included in the de novo CTO cohort, 85 treated with DCB and 85 with DES. The mean age was similar between the groups (64.46 ± 10.56 in the DCB group vs. 65.39 ± 64.46 years in the DES group, p = 0.31). Of the DCB group, 84% were male, while in the DES group, 85% were male. Overall, the baseline clinical characteristics were comparable between the two groups with no significant differences, as seen in Table 1.
Procedural characteristics
Table 2 presents the angiographic and procedural characteristics of the de novo CTO group. In the DCB group, the left anterior descending artery (LAD) was the most frequently treated artery (48%), whereas in the DES group, the right coronary artery (RCA) was most commonly treated (44%).

Table 1 Baseline clinical characteristics of patients undergoing DCB vs. DES PCI for de novo CTO
Characteristics | DCB group (n = 85) | DES group (n = 85) | p-value
Age (years), mean (SD) | 64.46 (10.56) | 65.39 (9.76) | 0.55
Male, n (%) | 71 (84) | 72 (85) | 0.83
Hypercholesterolemia, n (%) | 23 (27) | 30 (35) | 0.25
Hypertension, n (%) | 42 (49) | 48 (56) | 0.36
Prior MI, n (%) | 32 (38) | 28 (33) | 0.52
Prior PCI, n (%) | 34 (40) | 35 (41) | 0.88
CABG, n (%) | 6 (7) | 6 (7) | 1
Family history of CAD, n (%) | 27 (32) | 22 (26) | 0.40
COPD, n (%) | 4 (5) | 4 (5) | 1
Diabetes, n (%) | 22 (26) | 13 (15) | 0.088
Creatinine, mean (SD) | 88.99 (24.10) | 93 (24.56) | 0.28
eGFR, mean (SD) | 74.89 (14.44) | 70.64 (15.10) | 0.062
Ex-smoker, n (%) | 36 (42) | 28 (33) | 0.21
CTO, chronic total occlusion; DCB, drug-coated balloons; DES, drug-eluting stent; MI, myocardial infarction; PCI, percutaneous coronary intervention; COPD, chronic obstructive pulmonary disease; CABG, coronary artery bypass graft; CAD, coronary artery disease; eGFR, estimated glomerular filtration rate. Values are expressed as number (%), mean ± standard deviation (SD), as appropriate. Statistically significant at p < 0.05

Fig. 1 Flowchart depicting the de novo CTO cohort with excluded and included number of patients. Abbreviations: CTO, chronic total occlusion; DCB, drug-coated balloon; DES, drug-eluting stent; HES, hospital episode statistics; OOHCA, out of hospital cardiac arrest

The DES group exhibited a higher prevalence of vessel bending angle > 45° (20% vs. 8%, p = 0.028) and a higher J-CTO score (≥ 2) (29% vs. 16%, p = 0.045). The DCB group demonstrated a higher median syntax score (19.50 IQR (14, 23.50) vs. 16.50 IQR (11, 20.50), p = 0.045) and a median vessel diameter of 3.00 mm, IQR (2.50, 3.50) vs. 3.50 mm IQR (3.00, 3.50), p < 0.001.
The mean length of the treatment segment was significantly longer in the DES group compared to the DCB group (45.20 ± 23.77 vs. 38.09 ± 17.49, p = 0.028). The incidence of dissection post-DCB in the DCB group was 28%, of which 62.5% were NHLBI type B. There was one edge dissection post-DES in the DES group, which was treated with a stent. Suboptimal angiographic results were observed in 13% of patients in the DCB group compared to 5% in the DES group (p = 0.10).
Clinical outcomes
The median observed follow-up period was 3.67 years (IQR 0.14–8.17) in the overall de novo CTO cohort, 3.16 years (IQR 0.14–7.43) in the DCB group, and 4 years (IQR 0.25–8.17) in the DES group (p = 0.051). Clinical outcomes during follow-up are summarized in Table 3. The primary endpoint, TVR, occurred in 16 patients (9.4%) overall, 11 (12.9%) in the DCB group, and 5 (5.9%) in the DES group.

Table 2 Angiographic and procedural characteristics of patients in de novo CTO group

Characteristics	DCB group	DES group	p-value
(n = 85)	(n = 85)
Vessel treated
LAD, n (%)	41 (48)	35	(41)	0.35
LCx, n (%)	14 (16)	13	(15)	0.83
RCA, n (%)	30 (35)	37	(44)	0.27
Bifurcation, n (%)	22 (26)	17	(20)	0.36
Diffuse disease,	n (%)	37 (44)	40	(47)	0.64
Length of treated segment, mean (SD)	38.09 (17.49)	45.20 (23.77)	0.028
Vessel diameter, median (IQR)	3.00 (2.50,	3.50)	3.50 (3.00, 3.50)	< 0.001
Vessel size
Small (≤ 2.75 mm), n (%)	34 (40)	18 (21.2)	< 0.001
Large (≥ 3.00 mm), n (%)	51 (60)	67 (78.8)	< 0.001
Syntax score, median (IQR), n (%)	19.50 (14.00, 23.50)	16.50 (11.00, 20.50)	0.045
CABG/native CTO intervened, n (%)	2 (2)	4 (5)	0.41
Technique
Antegrade wire escalation, n (%)	83 (98)	77	(91)	0.094
NCB, n (%)	66 (78)	38	(45)	< 0.001
SCB, n (%)	76 (89)	77	(91)	0.80
Scoring balloon, n (%)	12 (14)	6 (7)	0.13
Rotational atherectomy, n (%)	2 (2)	2 (2)	1.00
J-CTO score components
Entry shape-tapered, n (%)	69 (81)	72	(85)	0.54
Entry shape-blunt stump, n (%)	16 (19)	13	(15)	0.54
Angiographic calcification, n (%)	66 (78)	75	(88)	0.066
Bending > 45°, n (%)	7 (8)	17	(20)	0.028
Occlusion length ≥ 20 mm, n (%)	39 (46)	48	(56)	0.17
Previous failed attempt, n (%)	9 (11)	11	(13)	0.63
J-CTO score (0–5)
Low (0–1), n (%)	71 (84)	60 (71)	0.045
High (2–5), n (%)	14 (6)	25 (29)	0.045
Dissection post-DCB/DES,	n (%)	24 (28)	1 (1)	< 0.001
NHLBI type, n (%)
A	6 (7)	N/A	N/A
B	15 (18)	N/A	N/A
C	3 (4)	N/A	N/A
Suboptimal result, n (%)	11 (13)	4 (5)	0.10
Acceptable angiographic result, n (%)	74 (87)	81 (95)	0.10
DCB, drug-coated balloon; DES, drug-eluting stent; LAD, left anterior descending artery; LCx, left circumflex artery; CABG, coronary artery bypass graft; NCB, non-compliant balloon; SCB, semi-compliant balloon; J-CTO, Japanese chronic total occlusion score; NHLBI, National Heart, Lung, and Blood Institute. Values are expressed as number (%), mean ± standard deviation (SD), and median with interquartile range (IQR) as appropriate. Statistically significant at p < 0.05

The clinically relevant adjusted factors include creatinine, between treatment groups in the unadjusted model. Other J-CTO, and vessel diameter. secondary outcomes, including cardiovascular death,
In unadjusted analysis, there was no significant differ- TV-MI, and any MI, also showed no significant difference in TVR between DCB and DES groups (unadjusted ences in unadjusted analyses. Within 30 days of PCI, no HR 2.33, 95% CI 0.81–6.74, p = 0.118). Similarly, the com- cases of acute vessel closure or thrombosis were observed in posite endpoint (unadjusted HR 1.15, 95% CI 0.59–2.23, either group. During follow-up, no target lesion thrombosis p = 0.686) and all-cause mortality (unadjusted HR 0.56, 95% occurred in the DCB group, whereas one late stent throm- CI 0.21–1.54, p = 0.262) showed no significant difference bosis was recorded in the DES group at 2 years.

Outcome | Number of events | Unadjusted
| DCB (n = 85), n (%) | DES (n = 85), n (%) | HR | 95% CI | p-value
TVR | 11 (12.9) | 5 (5.9) | 2.33 | 0.81–6.74 | 0.118
All-cause mortality | 6 (7.1) | 11 (12.9) | 0.56 | 0.21–1.54 | 0.262
Composite endpoint | 18 (21.2) | 17 (20) | 1.15 | 0.59–2.23 | 0.686
Cardiovascular death | 1 (1.2) | 3 (3.5) | 0.43 | 0.04–4.30 | 0.471
TV-MI | 2 (2.4) | 1 (1.2) | 1.89 | 0.17–20.79 | 0.605
Any MI | 4 (4.7) | 5 (5.9) | 0.89 | 0.23–3.35 | 0.860
Table 3 Summary of unadjusted hazard ratios of primary and secondary endpoints at a median observed follow-up of 3.67 years

TVR, target vessel revascularization; composite endpoint, composite of all-cause mortality, any MI, and TVR; MI, myocardial infarction; TV-MI, target vessel-myocardial infarction; HR, hazard ratios; CI, confidence intervals
Table 4 Multivariable Cox regression models adjusted for creatinine, J-CTO score, and vessel diameter

Variable (adjusted for)

TVR
HR (95% CI), p-value

All-cause mortality HR (95% CI), p-value

Composite endpoint HR (95% CI), p-value

DCB vs. DES (adjusted for creatinine) | 2.37 (0.82–6.87), 0.111 | 0.45 (0.16–1.29), 0.139 | 1.16 (0.60–2.26), 0.659
Creatinine | 1.01 (0.99–1.03), 0.436 | 1.04 (1.02–1.05), < 0.001 | 1.02 (1.01–1.03), < 0.001
DCB vs. DES (adjusted for J-CTO) | 2.30 (0.79–6.71), 0.128 | 0.61 (0.22–1.68), 0.336 | 1.25 (0.63–2.46), 0.524
J-CTO score | 0.88 (0.25–3.13), 0.846 | 1.71 (0.62–4.67), 0.298 | 1.69 (0.82–3.51), 0.155
DCB vs. DES (adjusted for RVD) | 1.91 (0.63–5.81), 0.252 | 0.52 (0.18–1.48), 0.221 | 1.09 (0.54–2.19), 0.818
Reference vessel diameter | 0.57 (0.23–1.43), 0.233 | 0.79 (0.34–1.88), 0.599 | 0.86 (0.47–1.58), 0.635

DCB, drug-coated balloon; TVR, target vessel revascularization; HR, hazard ratio; CI, confidence interval. Each outcome was analyzed using separate multivariable Cox models with stepwise adjustment for one prespecified covariate at a time (serum creatinine, J-CTO score, or reference vessel diameter). For each model, the HR for DCB vs. DES is presented together with the HR for the corresponding adjustment variable. Given the limited number of events, not all covariates were included simultaneously to avoid model overfitting

Fig. 2 Cumulative incidence curve showing the probability of TVR over time in the de novo CTO cohort, comparing DCB-only and DES-only strategies. Numbers at risk are displayed below the x-axis at yearly intervals. The x-axis represents time in months and is truncated at 60 months. Unadjusted HR from univariate Cox regression: 2.33 (0.81–6.74), p = 0.118

After adjustment for serum creatinine, J-CTO score, and reference vessel diameter, as depicted in Table 4, the use of DCB compared with DES was not associated with significant differences in target vessel revascularization, all-cause mortality, or the composite endpoint. In these models, creatinine was independently associated with a higher risk of all-cause mortality (HR 1.04, 95% CI 1.02–1.05, p < 0.001) and the composite endpoint (HR 1.02, 95% CI 1.01–1.03, p < 0.001), whereas J-CTO score and vessel diameter were not significantly associated with outcomes. Adjusted models were not performed for TV-MI, any MI, and cardiovascular death due to low event rates.
As shown in Figs. 2, 3, 4, and 5, cumulative incidence curves demonstrated comparable long-term event rates between DCB and DES for target vessel revascularization, all-cause mortality, and the composite endpoint and any MI respectively.

Discussion
Our SPARTAN-CTO study is the first to report long-term outcomes of DCB-only angioplasty versus DES-only angioplasty in de novo CTO, with a median follow-up of
3.67 years. The DCB-only strategy demonstrated comparable long-term safety and efficacy to DES, with no significant difference in TVR or secondary outcomes including TV-MI, any MI, CVD, all-cause mortality, and the composite endpoint. These findings support the feasibility of

Fig. 3 Cumulative incidence curve for all-cause mortality in the de novo CTO cohort comparing DCB- and DES-only strategies. Numbers at risk are displayed below the x-axis at yearly intervals. The x-axis represents time in months and is truncated at 60 months. Unadjusted HR from univariate Cox regression: 0.56 (0.21–1.54), p = 0.686

a “leave nothing behind” approach, even in complex CTO lesions.
Our findings align with the growing body of evidence supporting the use of DCB in CTOs. A recent meta-analy- sis conducted by our group, pooling ten CTO DCB studies (n = 1474 patients), demonstrated the safety of DCB-based CTO PCI compared to second generation DES [29]. However, these studies were limited by shorter follow-up durations and heterogeneity in both lesion type (de novo and IS-CTO) and treatment strategies (DCB, hybrid, DES). To address this, we report the long-term outcomes in a real- world cohort for the de novo strategy separately.

Fig. 4 Cumulative incidence plot showing estimated probability of composite endpoint during follow-up in the de novo CTO cohort comparing DCB- and DES-only strategies. Numbers at risk are displayed below the x-axis at yearly intervals. The x-axis represents time in months and is truncated at 60 months. Unadjusted HR from univariate Cox regression: 1.15 (0.59–2.23), p = 686

In our de novo CTO cohort, DCB-only strategy resulted in a TVR rate of 12.6% at a median follow-up of 3.67 years. Although TVR was numerically higher in the DCB group, the difference did not reach statistical significance, and the divergence in event curves likely reflects limited sample size rather than a true meaningful difference. The usefulness of revascularization as an outcome can be limited, as decisions to reintervene are influenced by variability in clinical judgment, patient preference, and local practice patterns, as highlighted by Lamelas et al. [33]. Accordingly, we believe that TVR may require cautious interpretation as it is considered an operator-driven soft endpoint.
More importantly, the hard clinical endpoints, including all-cause mortality and any MI, were numerically lower in the DCB group, with visible late separation of the mortality curves. Although the composite endpoint occurred at similar rates in both groups, the pattern differed: in the DCB cohort, the composite was predominantly driven by TVR, whereas in the DES cohort, it was driven more by all-cause mortality. This distinction is clinically relevant, as hard events carry greater prognostic significance than operator-driven revascularization. While these differences were not statistically significant, the numerically lower mortality in the DCB group represents a clinically meaningful observation when interpreting long-term outcomes.

Fig. 5 Cumulative incidence plot showing estimated probability of any myocardial infarction (MI) during follow-up in the de novo CTO cohort comparing DCB- and DES-only strategies. Numbers at risk are displayed below the x-axis at yearly intervals. The x-axis represents time in months and is truncated at 60 months. Unadjusted HR from univariate Cox regression: 0.89 (0.23–3.35), p = 0.860

Our TVR rates remain consistent with the previously reported de novo CTO studies—11.2% at 2 years in Jun et al. [34] and 8.2% at 3 years in Wang et al. [35]. The composite end point occurred in 21.2% of the DCB group versus 20% in DES group (unadjusted HR 1.15, 95% CI 0.59–2.23, p = 0.686). These findings align closely with DES-based CTO PCI trials. The DECISION-CTO randomized trial [36], which compared DES PCI against optimal medical therapy (OMT), reported no difference in any revascularization (14% vs. 11.8%, p = 0.38) or in the primary composite of death, MI, any revascularization, or stroke (22.3% vs. 22.4%, HR 1.03 95% C.I 0.77–1.37, p = 0.86). Similarly, the CONSISTENT-CTO trial [37] showed a 2-year overall MACE rate (all-cause mortality, MI, or TVR) of 17% and a TVR rate of 11.9% (25 of 210 patients) in the DES CTO PCI cohort. Taken together, our composite endpoint, which
included all-cause mortality, any MI, and TVR, is broadly comparable to these DES-based CTO PCI studies.
The absence of early vessel closure or acute and late target lesion thrombosis in our DCB group supports the favorable safety profile of this strategy. These findings are consistent with prior all-comers DCB studies, including the DEBUT trial [38], the EASTBOURNE registry [39, 40] at 12-month follow-up, and our SPARTAN registry [41] (0.17% in DCB group in 30 days post-PCI). Late stent thrombosis occurred in 1.2% (1/85) of patients in the DES group in 2 years, which is comparable with rates reported in CONSISTENT CTO trial (2.9%, 6 of 210 patients) [37] and large CTO registries [42, 43]. These comparisons highlight that our event rates are similar to these DES study event rates and suggest that DCB may represent a safe alternative to DES in the CTO setting.
Optimal lesion preparation is fundamental to the success of DCB-only PCI, particularly in chronically hypoperfused CTO lesions. While the primary aim of lesion preparation in angioplasty is to achieve adequate acute lumen gain, in CTOs, this goal often extends into a delayed response, owing to the phenomenon of positive vessel remodeling post recanalization. Such late lumen enlargement (LLE) is a well-documented physiological response [20, 29, 44]. This becomes particularly advantageous when coupled with the biological effects of DCB therapy in CTOs [35], which has been shown to support sustained LLE over time. In contrast, stent undersizing is not uncommon due to underestimation of vessel size, which may later enlarge, potentially leading to stent malapposition and adverse outcomes [45]. There is also a growing interest in investigating the performance of DCB when used after plaque modification in failed CTO cases to facilitate distal wiring during staged procedure [30]. An angiographic result with residual stenosis up to 50% can potentially be accepted to allow for DCB treatment [46] and for LLE to happen, as shown in studies by Shin et al. [47] and Wang et al. [35].
Moreover, recanalizing CTOs remains an inherently complex procedure, frequently involving heavily calcified, diffusely diseased, tortuous lesions with ambiguous proximal caps. J-CTO score predicts such procedural difficulty, success rates, and the technical expertise required. In our de novo CTO cohort, the mean J-CTO score was 1.8 ± 1.03 and a median Syntax score of 19.50 (IQR 14.0–23.5), indicative of a moderately complex lesion profile. Our center has developed a structured lesion preparation algorithm over more than a decade of experience treating complex lesions with DCB. This level of procedural expertise, along with more frequent use of NCBs in the DCB group, likely contributed to the low incidence of flow-limiting dissections.
CTO lesions are often diffusely diseased, requiring lengthy treatment devices. In our DCB-only group, the mean longest treated segment was 37.97 ± 17.31, whereas
in the DES-only group, it was 44.87 ± 24.14, p = 0.025. The GRAND-DES registry demonstrated stenting more than 40 mm is independently associated with less favorable outcomes, including higher rates of target lesion failure (IPTW adjusted HR 1.88, 95% CI 1.67–2.13; p < 0.001) and stent thrombosis (IPTW adjusted HR 2.20, 95% CI 1.51–3.20; p < 0.001), during median follow-up of 2 years [48]. A recent study by Shin et al. showed the DCB-based (hybrid) approach significantly and safely reduced the stent length and number by 66% and 63.9% respectively, when compared with the DES-only group, with an associated lower risk of MACE at 2 years (3.1% vs. 13.2%, p = 0.001) in the DCB group [47]. In that study, DESs were deployed in larger proximal CTO entry sites while distal small caliber segments were treated with DCBs, as a hybrid approach, minimizing the stent number and lengths. Our SPARTAN- CTO study has showed mean shorter treatment length in the DCB-only group. These results support the hypothesis that the DCB-only or hybrid approach allows for a reduction in stent burden potentially promoting favorable vessel healing, late lumen growth, and restoration of vasomotion in CTO lesions.
In our cohort, serum creatinine was independently associated with both all-cause mortality and the composite endpoint. Similar findings have been reported previously. Guo et al. [49] identified severe renal dysfunction as an independent predictor of MACE (HR 2.53, 95% CI 1.38–4.64), while Van Veelen et al. [50] demonstrated that renal insufficiency was the strongest predictor of 1-year mortality after CTO PCI (OR 5.59, 95% CI 3.25–9.59). These observations emphasize that renal dysfunction reflects a higher burden of diffuse atherosclerosis, systemic inflammation, and increased procedural risk in CTO patients. It is therefore of considerable clinical importance to carefully consider renal insufficiency in selecting patients for CTO PCI.
Our study findings are very relevant to contemporary clinical practice, which increasingly focuses on reducing stent-related failures by optimizing stent placement guided by intravascular imaging involving high procedural costs. IS-CTO, with increasing incidence, is independently associated with TVR, particularly in those with multiple stent layers [51]. The ability of the DCB strategy to safely minimize metal implantation and multiple layers may mitigate the long-term risks associated with IS-CTOs and reduce the incidence of this high-risk subset over time.
In summary, SPARTAN-CTO study supports the feasibility, safety, and long-term efficacy of DCB-only CTO PCI. By leaving no metal behind or by reducing the metal burden, especially in complex lesions, the advantages of DCB therapy may be achieved. However, it is crucial to recognize that successful DCB procedures require meticulous lesion preparation, operator experience, and careful patient selection.
Limitations
We acknowledge several limitations of our study. This was a retrospective, single-center, observational study, which may limit its generalizability and introduce potential biases. To minimize referral bias, all consecutive eligible cases from 2013 to 2019 were included. Baseline clinical characteristics were adjusted for in the analysis. Our CTO operators were experienced with both DCB and DES procedures, which could mitigate some selection bias risk. However, experience with DCB strategies increased gradually over the study period. The decision to use DCB or DES was not randomized and remained at the operator’s discretion, which could introduce bias. Relevant angiographic and procedural variables were adjusted for in multivariate models. Despite this, the possibility of unmeasured confounding cannot be excluded. We used only paclitaxel-coated DCBs, which may limit our findings to other DCB platforms.
Conclusions
With a median follow-up of 3.67 years, our SPARTAN-CTO study is the first to show long-term safety of the DCB-only approach in de novo CTO PCI compared to the DES-only approach. While the results are encouraging, larger prospective studies with longer follow-up are warranted to confirm the benefits of DCB-based strategies in CTO PCI.
Supplementary Information The online version contains supplementary material available at https://doi. org/ 10. 1007/ s00392- 026- 02852-3.
Acknowledgements SPARTAN-Norfolk consortium: Timothy Gilbert^a, Johannes Reinhold^a,b, Paul Richardson^a, Alisdair Ryding^a,b, Trevor Wistow^a, Sulfi Sreekumar^a, Chris Sawh^a, Clint Maart^a. ^aDe- partment of Cardiology, Norfolk and Norwich University Hospital, ^bDepartment of Medicine, University of East Anglia.
Data Availability Data can be made available following an appropriate request to the corresponding author.
Declarations
Conflict of interest Rajkumar Natarajan has no conflict of interests and has received no funding related to this study. Ioannis Merinopoulos has received investigator-initiated funding from Cordis. Natasha Corbal- lis receives a doctoral research fellowship grant from NIHR. Vassilios Vassiliou received grants for investigator-initiated research from B Braun. Simon Eccleshall received speaker fees and acts as a consultant for B Braun, Medtronic, Cordis, and MedAlliance, and received grants for investigator-initiated research from B Braun.
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