Three major findings arise from this study. (1) DCB has a comparable performance to DES in patients with SvCAD, in terms of procedural characteristics, where there are no significant differences between DCB and DES regarding acute gain, procedure time, fluoroscopy time and contrast volume. (2) Regarding angiographic outcomes within one year after SvCAD revascularization, in lesion LLL is significantly lower in patients treated with DCB, compared to those with PCI using DES. (3) Regarding long term clinical outcomes within one year, composite MACE, non-fatal MI, TLR, and major bleeding are more frequent in patients with PCI using DES. However, DCB doesn`t outperform DES in terms of cardiac death, TVR, and vessel thrombosis.
It is well known that PCI with DES has been widely used for CAD patients. PCI aims to improve the minimum lumen diameter in a culprit coronary segment [19] with subsequent increase immediately after the procedure but decreases at follow-up. This could be mainly attributed to recoil and hyperplasia phenomena. The amount of this neointimal hyperplasia is mainly independent of the vessel size and SvCAD is more prone to re-stenosis than larger coronary vessels [20].
In the SvCAD setting, the prospective Spirit SV study reported TLR rate of 10.8% after 13 months with Xience DES [21]. The cumulative data analysis of the SPIRIT and COMPARE studies shows a 2-fold risk of MACE versus larger vessels [22], with a significantly higher risk of MI and TLR. The TWENTE II study showed similar data, with a TLR rate of 9.5% versus 5.4% in larger vessels after two years, and a significantly higher risk of MI and TLR in the SvCAD setting [5].
Given these limitations of DES in terms of ISR and ST, DCB angioplasty has been shown to be a new revascularization modality for the treatment of SvCAD. To date, only few RCTs compared DCB angioplasty with DES in SvCAD, and thus the aim of this study was to assess the angiographic efficacy and long term clinical outcomes of DCB in treating patients with SvCAD as compared with DES.
The first DCB generation failed to prove the angiographic non-inferiority versus DES in the prematurely interrupted PICCOLETO trial that was the first RCT to compare DIOR paclitaxel-DCB and Taxus Liberte´ paclitaxel-DES in SvCAD [23]. This trial was terminated early due to a higher rate of TLR and MACE after six months. It was hypothesized that these findings could be attributed to lack of efficacy of the used DIOR paclitaxel-DCB that was later replaced by newer generation DCBs [24]. Similarly, SCAAR registry in Sweden between 2009 and 2017 supported this finding and reported an increased restenosis risk in patients undergoing PCI on SvCAD with DCB compared with DES, while there was no difference in all-cause deaths or vessel thrombosis [25].
By contrast, newer-generation DCB showed the potential advantages of using this modality in treating SvCAD. Regarding angiographic outcomes, the BELLO study documented the angiographic superiority of paclitaxel-DCB (IN.PACT Falcon) versus paclitaxel-DES (Taxus Liberte) in SvCAD patients during three year follow up [26]. Also, RESTORE SVD study showed that the Restore DCB was not inferior to a new generation DES regarding diameter stenosis with also no significant differences regarding LLL during one year follow up. This dramatic benefit of this newer DCB generation could be related to balloon pre-dilatation [27].
Concurrently, the present study revealed a favourable long term angiographic outcomes resulting from DCB, compared to DES in SvCAD patients. During one year follow up, the in-lesion LLL was significantly lower in patients treated with DCB in comparison to those with PCI using DES (P < 0.001). This could be explained by the fact that DCB delivers anti-proliferative drugs into vascular wall without implanting a stent mediating a suppression role on intimal hyperplasia and inflammation. Moreover, the use of DCB may theoretically overcome the risk of negative vascular remodelling obtained with plain balloon angioplasty, and both the immediate encumbrance and the subsequent neointimal proliferation after stent implantation may be reduced [28].
The PICCOLETO II study also confirmed this angiographic superiority evidenced by LLL, with comparable clinical outcomes at one year follow up. This could be attributed to a favourable effect of paclitaxel delivery by means of DCB with subsequent late lumen enlargement [29].
Regarding long term clinical outcomes resulting from the use of DCB compared to DES in SvCADs patients, the BELLO [26] and RESTORE SVD [27] studies showed a significant MACE reduction during three and one year follow up respectively in favour of DCB compared to DES. The BASKET-SMALL II trial was the largest RCT evaluating the safety and efficacy of DCB (Sequent Please DCB), versus DES (72% Xience, 28% Taxus) in SvCAD and showed comparable MACE rates between DCB (7.3%) and DES (7.5%) after one year follow-up [30]. Moreover, PICCOLETO II trial [29] supported these clinical findings and did not show any safety signal concerning DCB related to DES in SvCAD at mid-term follow-up, and was consistent with the data provided by BASKET SMALL II [30] and RESTORE SVD trials [27].
Interestingly, this study didn`t show only comparable findings concerning long term clinical outcomes resulting from DCB in treating SvCADs compared to DES, but also showed a significant composite MACE reduction during one year follow up (P < 0.001), specifically in terms of non-fatal MI (P = 0.04), TLR (P < 0.001), and major bleeding (P = 0.03).
In the meta-analysis conducted by Li et al [31], the efficacy of DCB and DES in SvCAD patients was compared and indicated that the DCB strategy was associated with decreased risk of non-fatal MI compared with the DES strategy, but there was no significant difference. The present study supported this finding with a significant difference, where non-fatal MI during one year follow up was more frequent in patients with PCI using DES compared to those treated with DCB (P = 0.04).
Recently, PEPCAD NSTEMI and REVELATION trials investigated the risk of TLR in DCB versus DES in an ACS setting during nine months follow up. The PEPCAD NSTEMI trial [32] stated that DCB treatment was non-inferior to stent treatment with a TLR rate of 3.8% versus 6.6%. The REVELATION trial [33] also stated that the mean fractional flow reserve was not different between DCB and DES at nine months follow up confirming this non-inferiority of a DCB in relation to DES in ACS patients.
Our study results are in line with the findings of the above mentioned trials; but supported these findings in SvCAD setting, where the risk of TLR was more frequent in DES compared to DCB during one year follow up (P < 0.001). This finding could be explained by the avoidance of permanent implants during DCB strategy and therefore preventing stent-related complications [34]. Accordingly, compared with DES, DCB was associated with a decreased risk of stent under expansion, ST, stent fracture, polymer damage, and stent gap.
The two and three year follow-up data were recorded for BASKET-SMALL II trial and showed a statistically significant reduction in the risk of major bleeding at two years follow up, with no difference at three years and a trend towards the DEB arm [35]. In line with these findings, the present study showed that the risk of major bleeding was more noted in SvCAD patients with PCI using DES, compared to those treated with DCB (P = 0.03).
This is mainly related to the need of long term anticoagulation after DES implantation because the arterial injury resulting from DES implantation could lead to subsequent vaso-proliferative cascade involving smooth muscle cell proliferation and migration and result in neointimal hyperplasia and even ST [34]. Thus, DCB could be a great alternative modality to deliver anti-proliferative materials without using metals and accordingly shorten the anticoagulation period and reduce the risk of major bleeding.
Limitations
The present study had some limitations. First, it is a single-centre study including a relatively small number of certain patients with SvCAD. Thus, multicentre studies with larger study populations will be needed to confirm the clinical relevance and efficacy of DCB in treating patients with SvCAD. Second, due to cross-sectional nature of this study, some ascertainment bias couldn`t be completely excluded. However, data processing and statistical analyses were performed by independent clinicians and statisticians. Third, these results have been obtained in a centre certified a strong leadership in the use of DCB, therefore it is possible that the results are not reproducible in a different scenario. Finally, the duration of the follow up is relatively short and a longer follow up period is recommended to better assess long term clinical and angiographic outcomes.