The role of drug coated balloons (DCB) in the landscape of interventional cardiology has been evolving and forthcoming several randomized clinical trials (RCT) are awaited to further define benefits and drawbacks, particularly in the treatment of de novo coronary artery disease compared to the commonly used drug-eluting stent (DES). The metal-free nature of DCB angioplasty may enhance vascular healing by preserving normal vasomotor function and facilitating positive vessel remodeling. One of the most appealing and attractive applications for DCB is small vessel coronary artery disease (SV-CAD) because of the well described lower performance of DES in this setting. The 1-year rate of TLR in SV-CAD is nearly doubled compared to lesions in larger vessels after DES implantation and, thus, an alternative is imperative to obviate this limitation and offer optimal strategies of coronary revascularization to patients [1]. Four RCT assessed the implication of using DCB in SV-CAD in comparison to DES [[2], [3], [4], [5]]. None of these trials was adequately powered to detect differences in clinical endpoints between treatment arms, with the exception of BASKET-SMALL 2, which was specifically designed to assess the non-inferiority of DCB. Nevertheless, the collective findings of these studies have reassured the interventional cardiology community regarding the safety and efficacy of DCB for the treatment of SVD-CAD, demonstrating outcomes at least comparable to those achieved with first- and second-generation DES. Moreover, the powered SVD subgroup analysis of REC-CAGEFREE I trial showed no difference between DCB and DES at 2-year follow up as pertains TLF (5.1 % vs. 4.4 %, p = NS) or other clinical endpoints [6].

In this issue of CRM, von Koch et al. report data from the Swedish Coronary Angiography and Angioplasty registry (SCAAR) focused on the comparison of DCB and DES for the treatment of SV-CAD [7]. This nationwide, retrospective, propensity score-adjusted analysis utilizes SCAAR data to assess outcomes between DCB and second- and third-generation DES in lesions less than 3 mm in diameter. The study evaluates 1439 pairs of DCB and DES treated segments with easy lesions (type A1/B) from 2016 through May 2024. Notably, the most treated vessels were: first diagonal branch, first obtuse marginal branch, distal left anterior descending artery, and right posterior descending artery, respectively. The primary outcome was a composite of TLR, target vessel myocardial infarction (TV-MI), and all-cause mortality at a mean follow-up of 3.5 years. Secondary outcomes included the individual components of the primary composite, as well as target vessel revascularization (TVR), any myocardial infarction (MI), and repeat PCI. Notably, DES demonstrated a statistically significant reduction in the primary outcome compared to DCB (14.7 % vs 19.2 % - HR, 0.76; 95 % CI, 0.61–0.95). Among the other endpoints, TV-MI was the only individual component found to be significantly lower in the DES group (3.4 % vs 1.3 % - HR, 0.52; 95 % CI, 0.29–0.94). Additionally, TVR (7.7 % vs 5.1 % - HR, 0.71; 95 % CI, 0.50–0.99) and any MI (9.5 % vs 7.0 % - HR, 0.72; 95 % CI, 0.53–0.98) were significantly lower in the DES group as well. No difference was accounted as pertains TLR, cardiac death, and repeat PCI. Additionally, no meaningful subgroup interactions were identified across any of the predefined patient characteristics.

The authors should be commended for their effort to provide novel evidence for such an important topic with current clinical relevance. The conduction and methodology of the study is consistent and reliable. This represents one of the larger retrospective analyses to date comparing DCB and DES in SV-CAD. Importantly, the study provides long-term follow-up data with an average follow-up of 3.5 years and data collected out to 5 years.

Nevertheless, several aspects of this study show major limitations and merit further discussion, and we deem of particular importance to put these findings into the context of a quite rich literature. First, it is important to acknowledge that this study is an observational, retrospective not prespecified cohort analysis, and thus inherently subject to limitations such as selection bias. Consequently, its findings should be interpreted in the context of existing evidence from several international, multicenter, prospective registries or RCT.

Second, many patients were treated before sufficient emphasis was given to a correct lesion interpretation (intravascular imaging use here is scant) and lesion preparation. In this study, the use of cutting balloons (0.7 %) intravascular lithotripsy (0.1 %) was negligible, and no data were provided on the pre-dilatation balloon-to-vessel or DCB-to-vessel ratios—key metrics for optimal lesion preparation [8,9]. This is particularly relevant given that heterogeneous lesion preparation may contribute to inconsistent device efficacy—especially considering the broad spectrum of DCB technologies employed in this study. To note, the lack of reported bail-out stenting rates limits our ability to assess the adequacy of lesion pre-dilatation, of which it is often an epiphenomenon. Third, the reported mean DCB inflation time of 31 s falls significantly below the generally recommended minimum of 60 s [[8], [9], [10]]. Notably, shorter inflation durations have been associated with higher rates of bail-out stenting with the beneficial effect of longer inflation that turns into reduced residual stenosis and atheroma volume [11,12]. Fourth, no independent core lab assessed all these items, including minimum lumen diameter and percent diameter stenosis, and no external clinical committee adjudicated the events.

Recently, the patient-level ANDROMEDA meta-analysis—which included individual data from three randomized trials and reconstructed time-to-event data from a fourth one—offered a more robust assessment of DCB efficacy in SV-CAD [13]. The analysis, encompassing 1384 patients and 1590 lesions, revealed a significant reduction in major adverse cardiovascular events in favor of DCB group compared to DES (18.5 % vs. 24.5 %, HR 0.75, CI 0.58–0.95) at 3-year clinical follow-up. These findings support the use of DCB angioplasty not only as a viable alternative to DES but potentially as a preferred strategy for managing SV-CAD, warranting renewed debates about formal inclusion of DCB in future clinical guideline recommendations.