Drug-coated Balloons for Small Coronary Disease—A Literature Review

Current Cardiology Reports (2021) 23: 173 https://doi.org/10.1007/s11886-021-01586-0 NEW THERAPIES FOR CARDIOVASCULAR DISEASE (AA BAVRY AND MR MASSOOMI, SECTION EDITORS) Drug‑coated Balloons for Small Coronary Disease—A Literature Review Ketina Arslani1 · Raban Jeger1 Accepted: 26 July 2021 / Published online: 14 October 2021 © The Author(s) 2021 Abstract Purpose of Review In the interventional treatment of coronary artery disease, new-generation drug-eluting stents (DES) currently are the standard treatment. In addition, drug-coated balloons (DCB) are a well-established option for the treatment of in-stent restenosis in both bare-metal stents (BMS) and DES, where DCBs deliver an antiproliferative drug without the necessity of re-implanting a stent. Since the field of use for DCB has increasingly been extended to other indications such as de novo lesions in small vessel disease (SVD), a review of literature may be useful. Recent Findings Recent randomized trial data show good efficacy and safety for DCB in de novo lesions, especially in small coronary arteries, and confirm long-term clinical efficacy and safety up to three years. Summary DCB are an attractive and safe option in the treatment of de novo lesions in SVD. Keywords Coronary artery disease · Small vessel disease · Drug-coated balloon · Drug-eluting balloon · Percutaneous coronary intervention Introduction Percutaneous coronary intervention (PCI) is the treatment of choice for patients with acute or chronic coronary artery disease (CAD) [1]. In the early days of PCI, the use of plain old balloon angioplasty (POBA) enabled the percutaneous treatment of CAD. Since then, the technique has evolved to the use of bare-metal stents (BMS), first-generation drug-eluting stents (DES), and second-generation and newer generation DES [2–5] as POBA was limited by elastic recoil, dissection, and restenosis. The development of these technologies eventually led to an optimization of efficiency and safety. However, in certain anatomical subsets such as small vessel disease (SVD), the use of DES is still challenging and seems to be associated with suboptimal results such as an increased risk This article is part of the Topical Collection on New Therapies for Cardiovascular Disease * Raban Jeger Ketina Arslani 1 Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH‑4031 Basel, Switzerland for in-stent restenosis (ISR) [6–10]. This constitutes a significant issue, as SVD is documented in up to 30% of patients with CAD undergoing PCI [11]. Drug-coated balloons (DCB) are an alternative treatment strategy for CAD based on the fast transfer of antiproliferative drugs into the vessel wall during balloon inflation and is an established option in patients with ISR [12, 13]. In de novo lesions in small coronary arteries, DCB has evolved to a valid alternative to DES as shown in several non-randomized trials and subsequently also in a large randomized multicenter study with similar rates of major adverse cardiac events (MACE) up to 3 years in patients treated either with DCB or secondgeneration DES [14••, 15•]. Methods After a detailed search of PubMed according to the established methods and in adherence to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement [16], this review includes only English language studies. The keywords used are as follows: “drug-eluting stents” OR “DES” OR “drug-eluting balloons” OR “drug-coated balloons” OR “DCB” OR “DEB”. Databases were screened up until 9 May 2021. The most 13 Vol.:(0123456789) 173 Page 2 of 7 recent and comprehensive data were used and, in addition, references from original and review articles were checked and included. Current Cardiology Reports (2021) 23: 173 Drug‑coated Balloons – Technology The International DCB Consensus Group suggested that a vessel of < 3 mm should be considered as “small”. SVD is therefore a lesion with a reference vessel diameter of < 3 mm [17]. SVD is fairly common and can be found in up to 30% of patients with symptomatic CAD. Specifically, patients with diabetes or chronic renal failure are more prone to develop SVD. Revascularization of SVD still represents a challenge due to the increased risk of adverse clinical events [8, 18]. Reference vessel diameter is defined as the average of diameter proximally and distally to the target lesion segment. A specific minimum lumen diameter (MLD) is aimed for when treating a vessel or lesion, which is based on the reference vessel diameter. MLD initially increases after the procedure and decreases at follow-up. Late lumen loss is defined as the difference between the postprocedural MLD and the MLD at follow-up (Fig. 1A). Preparation of the lesion and subsequent stent implantation leads to arterial injury and to neointimal hyperplasia. The quantity of neointimal hyperplasia is independent of the vessel size and thus the late lumen loss as an absolute number is similar in all vessel sizes [8]. Small vessels have a limited capacity to adapt to neointima formation without compromising blood flow after stent implantation and therefore restenosis occurs more often. It is natural that a minimal late lumen loss after treatment of SVD is crucial for optimal long-term results. DCBs are semi-compliant balloons with a coating of an anti-proliferative drug. The treatment strategy entails that the drug is rapidly and homogenously transferred to the vessel wall from a lipophilic matrix during single balloon inflation. Therefore, the vessel is treated without leaving any residue behind. The following factors are essential for the successful use of a DCB: choice of DCB, lesion preparation, and correct application of the specific balloon. The lipophilic matrix ensures an undamaged transfer through the vascular system to the site of application and makes a fast and homogeneous transfer of the medication into the vascular wall possible after inflation. Various DCBs are available for the treatment of coronary vessels. In most DCB, paclitaxel is still the most widely used antiproliferative drug with a dose between 2 and 3.5 μg/mm2. This highly lipophilic drug is embedded in a specific coating matrix and has proven to be effective as it is a potent antiproliferative agent and chemically stable. Successful drug transfer is dependent on coating formulation and technique of the procedure. Among others, carrier excipients such as iopromide, urea and shellac have been investigated for optimal drug delivery (Table 1) [19]. There has been some contradictory data on possible increased mortality in patients treated with paclitaxel-coated balloons and stents [20, 21]. However, the finding of increased mortality in patients with peripheral arterial occlusive disease treated with paclitaxel-coated balloons [20, 21] is based on a meta-analysis with major methodological limitations that prevent a reliable interpretation, while a large metaanalysis in patients with (...truncated)