CTO represents one of the most challenging procedures in PCI, accounts for approximately 20% of selective coronary angiography [1]. With advancements in CTO recanalization intervention technology and concepts, the success rate of recanalization continues to increase [4]. Compared to optimal medical therapy, successful PCI revascularization can effectively alleviate clinical symptoms related to myocardial ischemia and improve prognosis [3]. Although the newer-generation of DESs significantly reduce the incidence of restenosis and clinical adverse events, they still pose risks such as atherosclerosis due to their proinflammatory effect, stent thrombosis and stent malapposition [16]. Diffuse lesions in CTO typically require multiple stent or long stent implantation, which increases the risk of stent-related adverse events. Compared with DES, DCB can mitigate these risks, and in the absence of foreign implantation, short-term elution drugs can effectively prevent endometrial hyperplasia, which has been confirmed in several long-term follow-up DCB experiments [17, 18].

Initially, DCB was originally used to treat coronary ISR after BMS implantation [19]. Meanwhile, there is increasing evidence of the use of DCBs for the treatment of bifurcation and small vessel lesions [20]. Previous studies indicated that in small coronary lesions treated with DCB, the target lesion thrombosis rate was 0.6% at six months, with no event occurred during the final follow-up period of six months to three years [17]. The cell-inhibitory drugs delivered by DCB are released into the vasculature over a short period, contrasting with the six to twelve-month drug release period of DES. DCB has a broader and more homogeneous distribution of drugs in the vascular lumen than DES, which has a particularly beneficial effect in treating plaque-filled CTO lesions. We believe that successful recanalization of CTO lesions using DCB treatment can overcome the inherent drawbacks of stent implantation.

Our meta-analysis demonstrated promising outcomes for DCB treatment in CTO-PCI, showing a lower major adverse cardiovascular event (MACE) rate of 13.0%. In the DECISION-CTO trial [21], the MCAE (death, MI, stroke, or any revascularization) of the CTO-PCI group (receiving DES implantation) at three years was 21.5%, which was greater than our results. In addition, the incidence of cardiac death and TVR in DECISION-COTRIAL was 1.9% and 7.9%, respectively [21], This study showed comparable event occurrence rates (2.2% and 7.1%, respectively). However, as DECISION-COTRIAL is a single clinical trial, more studies are needed to compare the above data due to possible differences in study design, patient characteristics and treatment strategies.

In our study, the pooled rates of reocclusion and restenosis were 3.3% and 17.5%, respectively, among patients who underwent angiography follow-up. In the study by Onishi et al. to validate the efficacy of DCB treatment in de novo coronary artery lesions, including bifurcation and CTO lesions, the restenosis rate in the CTO lesion subgroup was 17% at 8.2 ± 4.0 months of follow-up after PCI [22], which was comparable to our results. Valenti et al. demonstrated that the restenosis rate was similar (12.5%) in CTO patients receiving DES treatment [23]. The risk of restenosis and stent thrombosis in CTO patients remains a challenging problem. One of the mechanisms is that stents are common in newly opened CTOs, and their size is too small because blood vessels do not immediately expand [24]. Due to the lack of blood flow for a long time, the distal vessel of CTO is narrowed. After balloon angioplasty, antegrade blood flow increases; however, it may take several weeks or months for blood vessels to dilate. Therefore, after CTO balloon angioplasty, it is easy to underestimate the actual size of the blood vessel, which increases the risk of inadequate stent size, poor stent adherence, and stent thrombosis [12]. Conversely, after DCB treatment, the blood vessels may recover to their original size in the future, without the need for stents to fix the size of the vessels. This is one of the most attractive and important advantages of using DCB to treat CTO lesions.

One of the main benefits of DCB in treating CTO lesions is the possibility of vascular remodeling over time. Previous reports have shown that 50-70% of non-CTO lesions treated with DCB exhibit LLE upon follow-up angiography and intravascular imaging [25, 26]. Scheller et al. first reported on LLE after DCB angiography in de novo coronary artery lesions and subsequently published a study using quantitative coronary angiography (QCA) analysis to evaluate LLE after DCB angioplasty [27]. After an average follow-up of 4.1 ± 2.1 months, 69% of patients developed LLE [28]. In our study, the summary estimate rate of LLE was 59.4% for CTO lesions. The possible mechanism of the enlargement of the vascular lumen likely involves apoptosis of smooth muscle cells (SMCs), as paclitaxel inhibits SMC proliferation and promotes proapoptotic factors through microtubule regulation [29]. Higher initial paclitaxel concentrations post-DCB compared to paclitaxel-eluting stents lead to mitotic arrest. Meanwhile, it has been confirmed in animal models that local application of paclitaxel can inhibit neointimal growth and facilitate arterial dilation [30]. However, research has shown that intracellular microtubules are specific binding sites for paclitaxel, mainly present in the subintima and adventitia [31]. Therefore, the retention of paclitaxel in these layers is significantly higher. when using DCB for subintimal recanalization, the local paclitaxel concentration may exceed the therapeutic effect within the toxic range, promoting excessive dilation of the vascular wall after DCB angioplasty, leading to coronary artery aneurysm. Another possible explanation of the enlargement of the vascular lumen might be arterial healing. Post-recanalization, the previously occluded segment undergoes extravascular remodeling due to long-term hypoperfusion. Over time, the restoration of anterograde blood flow and perfusion pressure helps to return the segment to its original size [13]. In addition, considering that most CTO segments contain organized thrombi rich in fibrin or proteoglycans in their occluded segments, the recovery of blood flow may promote the dissolution of organized thrombi, thereby further increasing the lumen [32]. Patients undergoing PCI must require daily dual antiplatelet therapy (DAPT) to prevent complications caused by thrombotic events. Another potential benefit is the shorter duration of DAPT and lower risk of bleeding events after DCB treatment, which is particularly important for patients with increased bleeding risk, measured by the CRUSADE score, or planning surgery shortly after PCI.

Detailed preoperative preparation and meticulous CTO PCI surgery are vital to reducing CTO vascular reconstruction and stent implantation [19]. The preparation of lesions has always been emphasized in DCB angioplasty to achieve optimal results [33], especially in CTO lesions. Adequate lesion preparation can increase the contact area between the surface of DCB and the endometrium, and local dissection without blood flow restriction can facilitate the delivery of antiproliferative drugs. Additionally, the combination of DES and DCB is an acceptable choice for the treatment of diffuse coronary lesions, reducing the risk of stent-related events by reducing stent use [34]. As is well known, the longer the stent length is, the higher the incidence of MACE. Meanwhile, DCB provides a “non-implantation” intervention option for cases of bifurcation or small vessel lesions in CTO recanalization to avoid imprisonment or small vessel cage formation caused by DES.

These ongoing trials related to DCB versus DES for treatment of CTO are crucial for advancing our understanding of the comparative effectiveness of DCB versus DES in the management of chronic total occlusions. By evaluating outcomes such as procedural success rates, recurrence rates, and long-term clinical outcomes, these trials can provide valuable insights into the optimal treatment strategies for patients with CTO. For patients who use DCB-only to treat CTO, especially those with complex features, more research is needed to explore the best revascularization strategies to ensure the best clinical outcomes. In summary, the current data seem to support the potential of DCB as a viable treatment option for suitable CTO patients.