The use of drug-coated balloons (DCB) to treat stenotic coronary artery lesions is a treatment strategy whose main asset is to avoid leaving a permanent intracoronary stent device. Although highly effective in the percutaneous coronary intervention setting, it is associated with a risk of acute thrombosis, future events like restenosis, and late thrombosis following processes known as neointimal proliferation, neoatherosclerosis or fractures of material. This could be even more relevant in younger patients with a long trajectory of possible coronary events ahead of them.
The use of DCB is widely accepted to treat in-stent restenosis and de novo lesions in small vessels1, and it is considered an interesting option in patients with high risk of bleeding. Another possible indication currently under scrutiny due to its possible potential is the management of bifurcations—one of the most interesting indications of all. However, clearly defined recommendations have not been established yet.2
Over the last few years, small clinical trials have been published on the use of DCB in this indication; although they have not proven definitive for a strong guideline recommendation, they provide valuable data. In general, trials have grouped into those looking into the safety and efficacy profile of DCB—without comparison group—and trials that compared strategies with DCBs or conventional balloons (CB).
PROSPECTIVE NON-RANDOMIZED TRIALS WITHOUT COMPARISON CONTROL GROUP
Table 1 shows 5 small trials (between 28 and 50 patients) including this type of different strategies with acceptable results regarding late lumen loss and safety.3-9
Table 1. Non-randomized, prospective clinical trials without comparison control group
| Trial | Name or author and DCB | No. of patients | LLL TLR events, and restenosis | Restenosis, and MACE |
|---|---|---|---|---|
| DCB into both branches and BMS into the main branch | PEPCAD-V4 (Sequent Please B. Braun, Germany) | 28 | 0.21 ± 0.48 in the SB 0.38 ± 0.46 mm in the MB Only 1 TLR (3.57%) and 3 restenoses (10.7%) | 2 patients (7.14%) had late thrombosis at 6 and 8 months |
| Paclitaxel DES into the MB, and DCB into the SB | DEBSIDE (NCT01485081) (Danubio, France) | 50 | LLL in the SB: -0.04 ± 0.34 mm and in the MB: 0.54 ± 0.60 mm TLR in 1 patient (2%) Restenosis, 7.5. | 1 AMI (2%) without cardiac deaths |
| -limus DES into the MB, and DCB into the SB | BIOLUX-A (www.anzctr.org.au, ID 335843) (Pantera Lux, Biotronik AG, SwitzeSBand) | 35 | LLL in the SB: 0.1 ± 0.43 mm 1 TLR (2.85%) No restenosis | 1 patient died, and 3 AMIs were reported in different vessels |
| SARPEDON5 (Pantera Lux, BIOTRONIK AG, Bülach, Switzerland) | 50 | TLR, 5.2% at 1 year 4% of restenosis in the MB, and 6% in the SB | Stent thrombosis, 0% | |
| Estudio de Valencia et al.6 (Sequent Please) | 54 | TLR, 3.6% | Overall mortality, 3.7% | |
| DCB alone into both branches | Schulz et al.7 (Sequent Please) | 39 | 10% restenosis, and all in the left main coronary artery bifurcation | |
| Bruch et al.8 (Sequent Please) | 127 | TLR, 4.5 | MACE, 6.1% Use of bailout stent in 45% | |
| DCB alone into 1 branch | Her et al.9 (Sequent Please) (Only in the MB) | 16 | There was a significant increase in the SB luminal area at 9 months, 0.37 mm2 ± 0.64 mm2; (P = .013), with a similar increase in the MB luminal area | The use of DCB alone in the MB also had a favorable impact on an area gain of 52% in the SB ostium |
| Vaquerizo et al. (NCT01375465) (Eurocor GmbH, Germany) (Only in the SB and 001 lesions) | 31 | LLL in the SB, 0.32 mm2 ± 0.73 mm2, and binary restenosis, and TLR of 22.5% | High need for bailout BMS (14%) 1 AMI (3.2%) | |
AMI, acute myocardial infarction; BMS, bare metal stent; CB, conventional balloon; DCB, drug-coated balloon; DES, drug-eluting stent; LLL, late lumen loss; MACE, major adverse cardiovascular events; MB, main branch; SB, side branch; TLR, target lesion revascularization. | ||||
TRIALS COMPARING THE RESULTS TO DIFFERENT STRATEGIES AND 2 COMPARISON GROUPS, MOST OF THEM RANDOMIZED
Table 2 shows the 6 landmark trials comparing different strategies, 5 of them randomized,10-14 and 1 non-randomized.15
Table 2. Trials that compared the results with different strategies in 2 randomized comparison groups (except for the one conducted by Li et al.15)
| Trial | Name and no. of patients | LLL | Restenosis and MACE, TLR events | Takeaway |
|---|---|---|---|---|
| DCB alone vs CB as a first-line therapy in lesions without damage to the proximal segment | PEPCAD-BIF10 (Sequent Please) 64 patients | LLL in the DCB group, 0.08 mm ± 0.31 mm vs 0.47 ± 0.61 mm in the CB group (P = .006). | Rates of restenosis of 26% vs 6% Rates of TLR of 9% vs 3% Favorable to DCB | In this type of lesions, stents were required in < 10% of the cases only |
| DCB vs CB in the SB with the use of BMS in the MB | DEBIUT11 (Dior-I, Eurocor GmbH, Germany) 117 patients A) DCB in both branches and BMS in the MB B) BMS in the MB, and CB in the SB C) Paclitaxel DES in the MB, and CB in the SB | LLL in the SB was 0.19 mm ± 0.66 mm in group A, 0.21 mm ± 0.57 mm in group B, and 0.11 mm ± 0.43 mm in group C (P = .001) LLL in the MB, 0.31 mm ± 0.48 mm in group A vs 0.16 mm ± 0.38 mm in group B (P = .15) | The rates of binary restenosis were 24.2%, 28,6%, and 15%; (P = .45), and the rates of MACE were 20%, 29.7%, and 17.5%; (P = .40) in groups A, B, and C, respectively | With this strategy, pretreatment of both branches with DCB was not superior to conventional BMS with the provisional stenting technique. Also, the use of DES was superior to DCB plus BMS |
| BABILON12 (Sequent Please) 108 patients A) DCB in both branches, and BMS in the MB B) Everolimus DES in the MB, and CB in the SB | LLL in the SB, –0.04 mm ± 0.76 mm in group A vs -0.03 mm ± 0.51 mm in group B (P = .983) | The rates of MACE and TLR were higher in group A in the MB (17.3% vs 7.1% [P = .10], and 15.4% vs 3.6%; [P = .045]) due to more restenosis in the MB (13.5% vs 1.8%; P = .027) | Bifurcation pretreatment with DCB with BMS in the MB had more LLL and higher rates of MACE vs DES in the MB and CB in the SB Also, both strategies gave similar and very good results in the SB | |
| Paclitaxel DES in the MB with CB vs DCB in the SB | Herrador et al.13 (Sequent Please) 50 patients | LLL, 0.40 mm ± 0.50 mm vs 0.09 mm ± 0.40 mm, (P = .01) favorable to the DCB group | The rates of SB restenosis were 20% vs 7%, (P = .08), and the rates of TLR, 22% vs 12% (P = .16) | The rates of MACE at 12 months were 24% vs 11% (P = .11) |
| -limus DES in the MB with CB vs DCB in the SB | BEYOND14, (Bingo, Yinyi Biotech, China) 222 patients with coronary bifurcation lesions excluding the left main coronary artery | Significantly lower LLL in the DCB compared to the CB group (–0.06 mm ± 0.32 mm vs 0.18 mm ± 0.34 mm; P < .0001) | The rates of restenosis were 28.7% vs 40% (P < .0001) | No differences regarding MACE (0.9% vs 3.7%, P = .16) or non-fatal AMI were found (0% vs 0.9%, P = .49) |
| Li et al.15 (Sequent Please) NON-randomized | LLL of SB in the DCB group was lower compared to the CB group (0.11 mm ± 0.18 mm vs 0.19 mm ± 0.25 mm; P = .024) at 12-month follow-up | Multivariate COX analysis indicated that the DCB group had less MACE (23.9% vs 12.8%; P = .03) | Better results in the SB with DCB and fewer composite endpoints, but basically at the expense of unstable angina | |
AMI, acute myocardial infarction; BMS, bare metal stent; CB, conventional balloon; DCB, drug-coated balloon; DES, drug-eluting stent; LLL, late lumen loss; MACE, major adverse cardiovascular events; MB, main branch; SB, side branch; TLR, target lesion revascularization. | ||||
CONCLUSIONS FROM TRIAL RESULTS
- 1. The use of bare metal stents (now in disuse) neutralizes all positive effects from the DCB in the main or side branch (DEBIUT11 and BABILON trials.12)
- 2. In lesions without proximal damage to the bifurcation, an early strategy of DCB can only be considered in 1 or in both branches (PEPCAD-BIF.10) Also, non-flow-limiting dissections have good prognosis at follow-up.
- 3. The use of DCB alone into the main branch can also have positive effects on the side branch ostium. Even using a limus-eluting stent in the main branch can only have a positive remodeling effect on the side branch ostium (aside from the study conducted by Her et al.,9 the BABILON trial already suggested it.12). In any case, the use of a DCB as a single stent-less strategy (unless results are poor or in the presence of flow-limiting dissections) seems like a reasonable option with a favorable long-term remodeling both in the main and side branches.
- 4. The use of a limus-eluting stent in the main branch with a DCB implanted in the side branch (currently the most widely used strategy) can improve angiographic intraluminal parameters like late lumen loss or minimum lumen diameter without any significant clinical repercussions on the long-term events (the BEYOND trial.14). This is probably so because, in the other group, late lumen loss in the side branch is also small since events are more conditioned by the main compared to the side branch (BABILON12), and also because there are barely any myocardial infarctions or target lesion revascularizations associated with the side branch in any of the 2 groups.
- 5. The results obtained with different balloons could also be different.
However, we should mention other aspects like vessel length, and not only vessel diameter since some studies demonstrate that length—and not diameter—can be a more important predictor of the impact side branch occlusion. Moreover, almost all these trials included side branch lesions < 10 mm in length, which is a well-known favorable predictor for the provisional stenting technique. Side branch lesions > 10 mm plus other signs of complexity like calcium, etc. can require the double stenting strategy, especially in left main coronary artery bifurcation lesions.16
Its role in more complex settings like left main coronary artery bifurcations or in-stent restenosis in bifurcations has also been studied, with reasonably good results.17,18
The article by Valencia et al.6 recently published in REC: Interventional Cardiology falls within the category of observational studies without control group that do not include angiographic measurements to allow, at least, a rough result comparison with other studies. This article combines treatment strategies like drug-eluting stent implantation into the main vessel in 71% of the cases or DCB alone into the main branch in 29% of the cases followed by DCB implantation into the side branch or DCB alone into the side branch, since 18% of the lesions were Medina 0,0,1 while, overall, 37.5% had no proximal damage.
According to the authors, this article contribution is the presentation of the clinical results of a small series of 54 patients with 55 lesions and the authors’ management of this type of lesions without excluding patients with higher risk of restenosis, as 32.1% of the patients with in-stent restenosis in the bifurcation and 8.9% with left main coronary artery lesions showed. Nevertheless the clinical outcomes are good with a median follow-up of 12 months. The rates of all-cause mortality, lesion thrombosis or infarction, and target lesion revascularization were 3.7%, 0%, and 3.6%, respectively, precisely in the most unfavorable cases of all, patients with in-stent restenosis.
The study limitations are obvious and well-established by the authors in the corresponding section. In brief, a small number of patients, no control group or angiographic follow-up, and the assumption that asymptomatic patients had no side branch restenosis. Also, since follow-up was not conducted on-site, possible developments of new Q waves associated with the side branch segment could not be detected. However, the study shows what many interventional cardiologists currently do in their cath labs and maintains interest for this strategy that should undoubtedly be taken into consideration when treating bifurcations. The most recent trials on drug-eluting stent and DCB implantation into the main and side branch, respectively, show good results in both branches, though with small differences in the repercussion of clinical events. Randomized clinical trials with a large cohort of patients are needed so that all possible trends favorable to the side branch become significant. Despite the presence of complex patients, the results from the trial conducted by Valencia et al.6 are good, promising, and their data welcome.
FUNDING
None whatsoever.
CONFLICTS OF INTEREST
None reported.
REFERENCES
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* Corresponding author.
E-mail address: lopez-minguez@hotmail.com (J.R. López-Mínguez).
