Intravascular brachytherapy vs. drug-coated balloons for in-stent restenosis in patients with diabetes

Background: Patients who have diabetes mellitus experience significantly higher rates of in-stent restenosis following percutaneous coronary intervention compared to the general population. The underlying pathophysiology of restenosis is exacerbated by diabetes-specific mechanisms including endothelial dysfunction, enhanced inflammatory response, and accelerated smooth muscle cell proliferation. While both intravascular brachytherapy (IVB) and drug-coated balloons (DCB) have been used to treat this condition, their comparative effectiveness in this high-risk population has never been evaluated in a long-term study. Objectives: To compare the efficacy and safety of IVB vs. DCB for the treatment of in-stent restenosis specifically in patients with diabetes. Methods: This dual-center study compared 2-year outcomes between patients with diabetes treated with IVB at Houston Methodist Hospital (USA) and DCB at Kaplan Medical Center (Israel). Propensity score matching was performed for age, sex, vessel size, and ejection fraction. Primary outcomes included all-cause mortality and target lesion failure (TLF). Results: DCB treatment was associated with shorter procedure times (58.2 ± 26.1 vs. 83.4 ± 37.2 min, p < 0.01) and reduced contrast use (121.5 ± 53.2 vs. 158.7 ± 73.5 mL, p = 0.03). In the propensity-matched cohort, MACE rates were similar (46.8% vs. 50.2%, p = 0.62). DCB treatment demonstrated significantly lower TLF rates compared to IVB (5.2% vs. 21.3%, p < 0.01) and reduced target vessel myocardial infarctions (3.9% vs. 15.6%, p = 0.01). Cardiac death rates were similar between groups (7.8% vs. 5.2%, p = 0.48). The mortality signal was particularly pronounced among patients with diabetes aged ≥65 years (HR 4.82, 95% CI: 1.05–22.17) and those with reduced ejection fraction (HR 3.15, 95% CI: 1.03–9.64), while the TLF benefit was consistent across most subgroups within the diabetic population. Conclusions: In this first-ever comparison with 2-year follow-up in patients with diabetes, DCB was associated with similar MACE rates and cardiac mortality rates compared to IVB but demonstrated significantly lower target lesion failure. These findings suggest that while DCB offers superior efficacy for ISR treatment in patients with diabetes, careful patient selection is crucial, particularly considering diabetes-related comorbidities that strongly influence overall survival.