In this study, conducted in a real-world setting, we compared patients treated with paclitaxel-DCB to those in two contemporary second-generation DES registries [8, 9] to evaluate the mid-term outcomes of DCB versus DES in patients with de novo, non-small coronary lesions.
Patients treated with paclitaxel-coated balloon (SeQuent Please, B. Braun, Germany) were consecutively enrolled in the REC-CAGEFREE registry (NCT05133921), which was a single-center, prospective study conducted in Xijing Hospital, China, between December 1, 2015, and December 1, 2019, aimed to document the real-world performance of the DCB in the non-small vessel (≥ 2.5 mm). The baseline of all participants (N = 2473) of the REC-CAGEFREE registry is provided in Additional file 1: Table S1.
Patients who received second-generation DES in the NANO [8] and HELIOS [9] registries were used as the comparator. The REC-CAGEFREE, NANO, and HELIOS registries were all conducted by the same group of investigators and used the same baseline and endpoint definitions. The NANO registry (NCT02929030) was a prospective, multicenter clinical registry conducted in 26 centers in China between August 1, 2016, and January 1, 2017, which enrolled 2481 consecutive patients treated exclusively with the Nano plus (Lepu Medical, China) sirolimus-eluting stent. The HELIOS registry (NCT03916432) was a prospective, multicenter study conducted in 38 centers across China between November 1, 2018, and December 1, 2019, which enrolled 3060 consecutive patients treated exclusively with the HELIOS (Kinhely Medical, China) sirolimus-eluting stent. The results of these two registries have been published previously [8, 9].
To compare DES to DCB, patients with de novo lesion, DES/DCB ≥ 2.5 mm in diameter, and had DES-only or DCB-only treatment were included; those who had STEMI, ISR lesions, DES bailout after DCB treatment, or a combined strategy of DES and DCB were excluded (Fig. 1). The definition of a small vessel is inconsistent across trials; however, to standardize the design of clinical studies and clinical decision-making, an expert consensus proposed using a reference vessel diameter of < 2.5 mm as the definition of small vessel coronary artery disease (CAD) [10] and was applied in the current study.
The study was performed in accordance with the Declaration of Helsinki and was approved by the ethics committees of the participant centers of each study. All the patients signed the written informed consent prior to participation.
PCI with DES or DCB was performed in accordance with international revascularization guidelines [4, 11] with the details of the NANO and HELIOS registries described previously [8, 9]. In brief, in the REC-CAGEFREE registry (DCB cohort), pre-dilatation of the target lesion was recommended using a non-compliant balloon, scoring balloon, or cutting balloon in a balloon-to-vessel ratio of 0.8-1.0. Commonly, a DCB treatment would only be performed after successful lesion preparation, defined as residual stenosis after pre-dilatation ≤ 30% by visual assessment based on at least two perpendicular angiographic views, a target vessel TIMI (Thrombolysis In Myocardial Infarction) flow grade 3, and the absence of a significant flow-limiting dissection which was no greater than type C [4]. The choice of diameter and length of DCB was left to the operator's discretion. Recommended inflation time was at least 45 s; however, the maximum inflation pressure and total inflation time were ultimately determined by the operator according to the patient's tolerance and the reaction of the treated lesions. As set out in the protocol of the REC-CAGEFREE registry, bailout stenting using a DES was strongly recommended if the target lesions/vessels post-DCB treatment failed to have a TIMI flow grade 3, dissection type less than type C, and residual diameter stenosis ≤ 30% by visual assessment.
The optimal balloon preparation subgroup was defined as exhibiting an optimal angiographic result after lesion preparation, including no dissection or type A, B, TIMI III blood flow, and residual stenosis (QCA) < 30% [12]. The optimal post-procedural caFFR was defined as caFFR value ≥ 0.89 after DCB angioplasty [13]. The optimal post-DCB subpopulation was defined as exhibiting an optimal angiographic result after DCB angioplasty, including no dissection or type A, B, TIMI 3 blood flow, and residual stenosis (QCA) < 30% [12].
The primary endpoint was the device-oriented composite endpoint (DoCE) defined as a composite of cardiovascular death, non-fatal target vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR). Other secondary endpoints of interest were the patient-oriented composite endpoint (PoCE) and the individual components of the DoCE and PoCE. PoCE was defined as a composite endpoint including all-cause death, any non-fatal MI, any stroke, and any repeat revascularization. The endpoints of all three studies were defined according to the Academic Research Consortium-2 recommendations [14, 15] and adjudicated by the independent clinical event committees of the same members. In the REC-CAGEFREE registry, angiograms pre- and post-DCB were analyzed using quantitative coronary angiography (QCA, Medis, Leiden, The Netherlands) [16] and caFFR (Rainmed Ltd, Suzhou, China) [17], with details provided in Additional file 1: Methods.
In both the NANO and HELIOS registries, patients were contacted at 1, 6, and 12 months by scheduled outpatient clinic visits. After 12 months, they were contacted by phone annually to assess the clinical status and adverse events. In the REC-CAGEFREE registry, patients were contacted at 1 month and 12 months by scheduled outpatient clinic visits and by phone contact annually thereafter. The median follow-up of REC-CAGEFREE, NANO, and HELIOS registries were 2.4 (1.8-3.2), 3.1 (3.0-3.1), and 2.0 (2.0-2.1) years, respectively. A total of 290 of patients (7.6%) in the DES arm (NANO and HELIOS registries) and 42 (5.0%) in the DCB arm (REC-CAGEFREE registry) were lost to follow-up.
Continuous data were expressed as mean ± SD and categorical data as absolute numbers and proportions. Wilcoxon rank-sum test or the Pearson chi-square test was used to compare patients' demographic, clinical, and procedural characteristics. The percentage of missing values are presented in Additional file 1: Table S2 in the Supplementary information. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for each outcome at the time point of interest, and the proportional hazard assumptions were tested and met in all models. To reduce the confounding bias of baseline characteristics, two statistical approaches, including inverse probability of treatment weighting (IPTW) and 1:1 propensity score matching (PSM), were performed [18]. The variables included in these adjustments are listed in Additional file 1: Methods. Kaplan-Meier was used to illustrate the outcomes between groups. We also used restricted cubic splines to flexibly fit the association of device diameters (DCB and DES) and clinical outcomes. Analyses were performed using R-project version 4.3 (R Foundation, Vienna, Austria). A two-sided P value less than 0.05 was considered statistically significant.