Drug-coated balloons reduce major adverse cardiac events in select coronary bifurcation lesionsDrug Coated Balloons Show Promise for Coronary Artery Disease

Coronary bifurcation lesions account for approximately 15%–20% of all percutaneous coronary interventions (PCI) and remain among the most technically demanding scenarios in interventional cardiology. Provisional stenting—stenting the main vessel and intervening on the side branch (SB) only when necessary—is the default strategy, yet SB ballooning's role remains contested and is frequently applied reflexively. This review advances a single, evidence-based argument: SB ballooning should be deployed selectively, governed by physiology and intracoronary imaging rather than angiographic appearance, and reserved for the anatomical subsets in which it confers genuine benefit. We marshal the supporting evidence along four lines. First, mechanism: carina shift, rather than plaque shift, is a frequent and often dominant contributor to ostial SB compromise and is generally well managed without routine ballooning. Second, randomized data on strategy: in SMART-STRATEGY a conservative SB approach did not worsen long-term outcomes relative to an aggressive one and was associated with lower 3-year target-vessel failure (11.7% vs. 20.8%; a modest, single-centre, borderline-significant trial), with less periprocedural injury; EBC MAIN found no significant difference between stepwise provisional and systematic two-stent treatment in less-complex left-main bifurcations, supporting stepwise provisional stenting as default, whereas a planned two-stent strategy reduced target-lesion failure in the more complex, DEFINITION-defined subset (DEFINITION II)—so these trials should not be conflated. Third, technique optimization under imaging: the proximal optimization technique and judicious kissing-balloon inflation refine the result, and intracoronary imaging improves procedural assessment, rewiring verification, balloon sizing and optimization, while randomized trials support the clinical benefit of imaging-guided PCI in complex lesions (OCTOBER for OCT-guided bifurcation PCI; RENOVATE-COMPLEX-PCI for imaging-guided complex PCI generally)—neither trial randomized distal-cell rewiring or side-branch ballooning itself. Fourth, the device decision when the SB must be treated: the DCB-BIF randomized trial and a 2025 meta-analysis (pooled odds ratio for major adverse cardiac events 0.48) show a drug-coated balloon is a promising, evidence-supported option outperforming plain (uncoated) balloon angioplasty in appropriately selected compromised side branches, not a default for every side branch requiring dilatation. Integrating these strands, we propose a practical, lesion- and physiology-specific framework and identify principal evidence gaps future trials should address.