Background: Native vessel coronary artery disease represents 1 of the most attractive fields of application for drug-coated balloons (DCBs). To date, several devices have been compared with drug-eluting stents (DESs) in this setting with different outcomes.

Objectives: The authors sought to compare the short- and long-term performance of the paclitaxel DCB with the everolimus-eluting stent in patients with de novo lesions in small coronary vessel disease.

Methods: PICCOLETO II (Drug Eluting Balloon Efficacy for Small Coronary Vessel Disease Treatment) was an academic, international, investigator-driven, multicenter, open-label randomized clinical trial in which patients were allocated to a DCB (n=118) or DES (n=114). We previously reported the superiority of DCBs regarding in-lesion late lumen loss at 6 months. Herein we report the final 3-year clinical follow-up with the occurrence of major adverse cardiac events (MACEs), a composite of cardiac death, nonfatal myocardial infarction, target lesion revascularization, and its individual components. Results: The 3-year clinical follow-up (median 1,101 days; IQR: 1,055-1,146 days) was available for 102 patients allocated to DCB and 101 to DES treatment. The cumulative rate of all-cause death (4% vs 3.9%; P=0.98), cardiac death (1% vs 1.9%; P=0.56), myocardial infarction (6.9% vs 2%; P=0.14), and target lesion revascularization (14.8% vs 8.8%; P=0.18) did not significantly differ between DCBs and DESs. MACEs and acute vessel occlusion occurred more frequently in the DES group (20.8% vs 10.8% [P=0.046] and 4% vs 0% [P= 0.042], respectively).

Conclusions: The long-term clinical follow-up of the PICCOLETO II randomized clinical trial shows a higher risk of MACEs in patients with de novo lesions in small vessel disease when they are treated with the current-generation DES compared with the new-generation paclitaxel DCB. (Drug Eluting Balloon Efficacy for Small Coronary Vessel Disease Treatment [PICCOLETO II].