Percutaneous coronary intervention (PCI) was historically performed without stent deployment, a technique that is currently referred to as plain old balloon angioplasty (POBA) (1). Outcomes of POBA were, however, compromised by acute vessel closure immediately and restenosis at follow-up (2). Coronary stents, initially bare metal and subsequently drug-eluting stents (DES), were, therefore, developed to overcome these issues. The vast majority of PCI procedures performed currently use DES. However, this leads to permanent metal implantation in the vessel with potential long-term consequences, including late stent thrombosis and restenosis. PCI with drug-coated balloons (DCBs) offers the advantage of leaving no metallic struts in the vessel and avoiding restenosis due to antiproliferative medication delivered by these devices (3, 4).

The DCB-only strategy has become an established treatment for in-stent restenosis (ISR) (4). A large number of clinical studies have also shown that DCB-only strategy provides optimal results in the treatment of native small-vessel disease (5). A long-term 5-year follow-up study has reported that DCB PCI for stable, de novo, coronary artery disease has similar results compared with second-generation non-paclitaxel stents (6). Recently, several observational studies have suggested that DCB-only PCI of de novo lesions in large coronary vessels is also safe and effective (7, 8). However, follow-up period in these studies is typically less than 12 months and proportion of coronary bifurcation lesions is small or undefined. Data for long-term efficacy of DCB-only strategy for native bifurcation and non-bifurcation lesions of large coronary vessels are currently limited. We, therefore, conducted this cohort study to determine long-term clinical outcomes of DCB-only therapy for de novo lesions of large coronary vessels. At the same time, we compared DCB-only PCI in bifurcation vs. non-bifurcation lesions.

To the best of our knowledge, this is the first specific study to evaluate the long-term efficacy of DCB-only approach for treating de novo lesions of large coronary vessels and compare bifurcation with non-bifurcation lesions. Our study demonstrated that (1) the TLF and TVR were low in de novo coronary lesions of large coronary vessels at long-term follow-up and (2) DCB-only strategy was safe and effective to treat de novo coronary bifurcation lesions of large coronary vessels.

Drug-coated balloons are semi-compliant balloons coated with antiproliferative agents that are released into the vessel wall after inflation (10). Once a coronary lesion has been adequately prepared without any significant residual stenosis and major dissection, then all what is needed is an antiproliferative agent to reduce neointimal proliferation and avoid post-angioplasty restenosis (11). Optimal lesion preparation is the key to successful DCB angioplasty. The recent consensus recommended a semi- or non-compliant with a balloon-to-vessel ratio of 1:1 (4). However, in our study, the pre-dilation balloon diameter/RVD ratio was about 0.77. More than 50% target vessels had severe stenosis and complex lesions, which may account for this phenomenon. Despite the use of cutting balloon in 85% lesions, no patient suffered major dissection or acute vessel closure requiring bailout stenting. This may be due to conservative balloon sizing and hence residual stenosis in 29%. Nevertheless, TLR rate remained low. Similar results have also been reported in recent randomized studies (12).

Evidence is growing for efficacy of DCB-only strategy in the treatment of de novo lesions in large coronary arteries. However, the follow-up time in most of these studies is less than 1 year. In our study, the average reference diameter was 3.1 ± 0.3 mm and the median follow-up time was 2 years. The incidence of TLF and TVR was low (both were 4.2%). Similar results have been shown in recent short- or mid-term studies. The DEBATE study enrolled 119 patients (135 de novo lesions) with reference vessel diameter 3.1 ± 0.3 mm. TLR and TVR at 12 months follow-up were 3.4 and 5.1%, respectively, with no cardiac death or MI (13). Similarly, another prospective study reported TLR and major adverse cardiac event (MACE) rates of 4.3%, with no MI or death (14). Interestingly, a retrospective study analyzed 222 patients with RVD ≥2.8 mm, and there was no TLR and MACE at an average of 10 months of follow-up (7). DCB-only strategy for native lesions of large coronary vessels has also shown promising results for specific indications, for example, patients with high bleeding risk or patients with complex acute coronary syndrome (15, 16). Moreover, the incidence of TLF with DCB was comparable to TLF with newer-generation DES. The TLF rates were 3.8 and 6.6% for the DCB and DES groups (p = 0.53) in PEPCAD NSTEMI trial (17). Similar results were also seen in the REVELATION study (18). However, this may be due to younger age of patients and relatively uncomplicated lesions treated in DCB studies. It is also postulated that the benefit of DCB may be time-dependent and studies with very long-term follow-up are needed to confirm it.

Coronary bifurcation lesions are still a challenge for PCI, with relatively lower success rate and higher complication rate (19). DCB-only strategy has a theoretical advantage of respecting the original anatomy of bifurcation, especially carina. It also avoids jailing the side branch. However, data for DCB-only in the treatment of coronary bifurcation lesions in large coronary vessels are limited. In an observational study, 39 patients with de novo bifurcation lesions and SB ≥2 mm were treated with DCB-only strategy (20). At 4-month follow-up, three patients (7.7%) suffered TLR and MACE, but no patient had cardiac death, MI, or stroke. Another observational study enrolled 70 patients (70 lesions), of whom 51 (73%) had true bifurcation lesions (21). The rates of TLR (4.5%) and TVR (6.1%) were low at 9-month follow-up. The randomized PEPCAD BIF trial compared DCB angioplasty to POBA in bifurcation lesion of Medina type 0, 0, 1 or 0, 1, 0 or 0, 1, 1 (22). Only one patient (3.1%) had TLR at 9-month follow-up. Although promising results have been shown in the above studies, most of them were either in small vessels or at short-term follow-up. Therefore, we explored the long-term efficacy of DCB-only strategy in bifurcation lesions of large vessels. Our study had 66 patients (75 lesions) with RVD 3.0 ± 0.3 mm, 24.0% with true bifurcation lesions, 72.0% with B2/C complex lesions, and 2-year follow-up. One patient experienced periprocedural myocardial infarction. Reassuringly, no patient suffered TLR and TVR in the bifurcation group. However, the cumulative incidence and Cox regression analysis of TLF were not statistically different between the two groups, which may represent relatively modest sample size. Although optimal approach for bifurcation PCI remains debatable (23, 24), DCB-only strategy offers an attractive and potentially effective alternative. A prospective randomized multicenter trial with a large number of participants is warranted to confirm the value of DCB-only in de novo bifurcation lesions of large coronary arteries.

There are several limitations. First, there was no routine angiographic follow-up in this study; however, one may argue that clinical outcomes are more important and relevant and indeed incidence of angina pectoris and TLR were low. Second, although the angiographic images for residual restenosis were reviewed by experienced interventionalists, the absence of quantitative coronary angiography assessment, which may lead to underestimation of residual stenosis. Third, as an observational study, selection biases cannot be excluded. Finally, although we studied outcomes at a median follow-up of 2 years, due to modest sample size, low incidence rates, and potential DCB benefits at very late time points, it remains desirable to study outcomes at even longer follow-up.

This prospective observational study suggests that DCB-only strategy appears safe and effective for the treatment of both bifurcation and non-bifurcation lesions in native large coronary arteries.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Ethical Review Board of Xuzhou Third People’s Hospital. The patients/participants provided their written informed consent to participate in this study.

Y-JZ and X-XT: supervisors of the study and guarantee the study data and accuracy. F-WH, SC, and QL: conception, design, analysis, and interpretation of data. F-WH, Y-JZ, and JI: drafting and revising of manuscript and final approval of the manuscript submitted. F-WH, Y-XZ, X-YW, Y-WC, Q-HZ, and BL: data collection, data analysis, and interpretation. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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