BackgroundThe economic impact of drug-eluting stent (DES) in-stent restenosis (ISR) is substantial, highlighting the need for cost-effective treatment strategies. HypothesisCompared to plain old balloon angioplasty (POBA) or repeat DES implantation, drug-coated balloon (DCB) angioplasty is a cost-effective therapy for DES-ISR. MethodsA Markov state-transition model was used to compare DCB angioplasty with POBA and repeat DES implantation. Model input parameters were obtained from the literature, and the cost analysis was conducted from a German healthcare payer's perspective. Extensive sensitivity analyses were performed. ResultsInitial procedure costs amounted to Euro3488 for DCB angioplasty and to Euro2782 for POBA. Over a 6-month time horizon, the DCB strategy was less costly (Euro4028 vs Euro4169) and more effective in terms of life-years (LYs) gained (0.497 versus 0.489) than POBA. The DES strategy incurred initial costs of Euro3167 and resulted in 0.494 LYs gained, at total costs of Euro4101 after a 6-month follow-up. Thus, DCB angioplasty was the least costly and most effective strategy. Base-case results were influenced mostly by initial procedure costs, target lesion revascularization rates, and the costs of dual antiplatelet therapy. ConclusionsDCB angioplasty is a cost-effective treatment option for coronary DES-ISR. The higher initial costs of the DCB strategy compared to POBA or repeat DES implantation are offset by later cost savings.