Regional Differences Between Drug-Coated Balloons and Drug-Eluting Stents in De Novo Coronary Disease

Abstract

Background: Randomized trials of drug-coated balloons (DCBs) versus drug-eluting stents (DESs) for de novo coronary artery disease (dnCAD) are confined to Europe and Asia, raising the question of whether outcomes vary by region. We aimed to examine whether outcomes differ between regions and, if so, whether any difference reflects geography itself or trial-level confounding.

Methods: PubMed, Embase, and Cochrane Central were searched for randomized trials comparing DCB with DES in dnCAD. Incidence rate ratios (IRRs) were pooled with a random-effects model (DerSimonian-Laird; Hartung-Knapp confidence intervals (CIs)). The pre-specified primary question was regional (Europe vs Asia) subgroup comparison of a harmonized device-oriented composite outcome (DOCO). To determine whether any regional signal reflected geography itself or trial-level confounding, we performed subgroup-aware leave-one-out analysis and examined two alternative explanations post-hoc: vessel-size inclusion and dominance of the single largest trial. We also descriptively examined comparator-DES generation across trials.

Results: Thirteen trials (4,673 randomized patients) were included; the primary DOCO analysis comprised 12 trials (4,396 patients). DOCO did not differ overall (IRR = 1.00; 95% CI, 0.70–1.44; I² = 49.1%). The pre-specified regional difference was statistically significant (Europe IRR = 0.83; 95% CI, 0.44–1.57; Asia IRR = 1.48; 95% CI, 1.04–2.11; subgroup P = 0.04) but was not robust on subgroup-aware leave-one-out analysis: the subgroup-interaction P value rose above 0.05 in eight of 12 iterations, most prominently on omission of REC-CAGEFREE I (about 49% of randomized patients; subgroup P value from 0.04 to 0.46), indicating a regional contrast driven by trial-level imbalance rather than geography. Vessel size and comparator-DES generation differed systematically between regions. No secondary endpoint differed overall, including cardiac death (IRR = 1.20; 95% CI, 0.94–1.52). All 13 trials used paclitaxel-coated balloons.

Conclusions: The apparent regional difference appears largely attributable to trial-level confounding (vessel size, comparator generation, single-trial dominance) rather than to geography itself. Because the randomized evidence comes only from Europe and Asia, these findings show that the Europe–Asia difference is not robust, but do not rule out geographic effects in other regions. Because all current randomized evidence is paclitaxel-specific and confined to Europe and Asia, globally representative trials of limus-coated balloons against contemporary DES are required.