Mechanism-guided therapy for in-stent restenosis: imaging and drug-coated balloons over anatomy aloneNewer strategies and imaging help treat blocked heart stents

This narrative review addresses the pathophysiology and treatment of coronary in-stent restenosis (ISR), arguing for a shift from anatomy-based management toward mechanism-guided, individualized therapy. The authors synthesize three main drivers of ISR: neointimal hyperplasia, neoatherosclerosis, and mechanical factors such as stent underexpansion or fracture. They emphasize that intravascular imaging with IVUS and OCT can enable mechanism-guided lesion preparation and device selection.

For treatment, the review identifies drug-coated balloons and repeat drug-eluting stent implantation as the principal strategies. It also notes that intravascular lithotripsy may help in severely calcified or resistant underexpanded lesions. Emerging biological factors, including sphingolipid metabolism, mitochondrial dysfunction, immune-inflammatory signaling, and systemic metabolic modulation, are discussed as potential future targets.

The authors acknowledge that the clinical relevance of these emerging biological factors requires validation. No quantitative estimates, comparative outcomes, or safety data are provided in this review. As a narrative synthesis, it does not offer pooled effect sizes or systematic assessments of study quality.

In practice, the review supports considering intravascular imaging to identify the dominant mechanism of restenosis and tailoring treatment accordingly, while recognizing that evidence for emerging biological targets remains preliminary.