Rationale and Design of a Prospective, Open Label, Randomized, Multicentric Clinical Trial: Drug Coated Balloon for Side Branch Treatment vs. Conventional Approach in True Bifurcation Coronary Disease: PRO-DAVID

Bifurcation lesions (BL) on coronary arteries account for 15-20 % of all performed percutaneous coronary interventions (PCI). Preferred approach for treatment of most bifurcation lesions is the stepwise provisional stent strategy with main branch-only stenting followed by provisional balloon angioplasty with or without stenting of the side branch (SB). Stenting of the side branch is indicated when the angiographic result in SB is clearly suboptimal and when flow remains reduced. Upfront use of two stent techniques may be indicated in very complex lesions with large calcified side branches ( most likely to supply at least 10% of fractional myocardial mass), with a long ostial side branch lesion (>5mm) or anticipated difficulty in accessing an important side branch after main branch stenting, and true distal LM bifurcations.

For non-left main bifurcation lesions consensus is that there is no systematic advantage to a more complex dual-stent implantation technique. For true left main lesions EAPCI/EACTS revascularization guidelines gave a IIb recommendation for double-kissing crush two-stent strategy compared to the provisional approach, based on the results of DKCRUSH-V Trial. EBC perspectives, even for the stenting on left main coronary true bifurcation lesions, is that they are best treated with a planned single-stent strategy rather than a planned dual-stent strategy. When a two-stent strategy is used, this will become apparent during a provisional stepwise approach, and finalizing the procedure using a culotte technique or occasionally TAP is recommended.

PCI strategies for complex coronary bifurcation lesions should be individualized, taking into account the anatomical differentiation of coronary bifurcation lesion differences, disease burden and complexity, but also the technical skills and experience of the operator. In daily clinical practice where less experienced operators with limited number of true bifurcations annually are faced with the challenge of treating complex bifurcation lesions, it is imperative to find a standardized and universal approach which would be simple, quick and safe, with a high percentage of procedural success, with a small number of complications, good long term results, with small expenditure of material and contrast volumes, and shorter procedure and fluoroscopy times.

Drug-coated balloon (DCB) technology allows to bring high concentration of an antiproliferative drug with immediate and rapid local delivery even with short contact times between the balloon surface and the vessel wall, sufficient for effective drug delivery without a durable polymer and further permanent metal prosthesis. The application of DCB in SB is an attractive and intriguing solution in treating complex BL. Rationality of such an approach lies in the many theoretical advantages of DCB. The application of DCB in SB respects the original anatomy of bifurcation, which is especially important in the carina area, and allows for the homogeneous application of a high dose of antiproliferative drug on the entire blood vessel surface and avoids the risk of incomplete coverage of the bifurcation area. In the case of a successful DCB application in the SB, unnecessary use of the stent is avoided, obviating long-term problems such as stent malposition and fracturing, scaffolding of the SB ostium, overlapping and crushing of multiple metal layers and polymers with uncontrolled drug release, and therefore re-stenosis and thrombosis and reactions to a foreign body. Even for the simplest provisional technique, the application of DCB has a theoretical advantage over the application of a regular balloon, with the expected positive remodelling of the vessel and plaque stabilization, and better late angiographic results, as well as neoatherosclerosis.

From a technical point of view, we propose a "Provisional DCB approach" that differs from the standard provisional approach with obligatory SB predilation and good lesion preparation. In case of an adequate result of predilation, the procedure on the SB ends with the DCB deployment. This is followed by main branch stenting with DES, finished with POT. Final 'kissing' balloon dilation is generally not recommended because there is no advantage from final kissing with the one-stent technique. With this approach, there is no need for re-wiring, re-ballooning, side branching and wire jailing and final kissing. This technique is close to a contemporary approach to bifurcation lesions based on the fundamental philosophy of the European Bifurcation Club (EBC): keep it simple, systematic, and safe, with a limited number of stents that should be well apposed and expanded with limited overlap, with respect of the original bifurcation anatomy.