Cutting vs standard balloon for lesion preparation in drug-coated balloon-only PCI: the NATURE randomised trial

Abstract The success of drug-coated balloon (DCB) therapy for de novo coronary lesions relies on optimal lesion preparation. However, evidence supporting the use of cutting balloons (CBs) for lesion preparation in DCB-only strategies remains limited. The NATURE trial assessed the effectiveness of CB compared with standard balloon (SB) predilatation in achieving optimal lesion preparation for a DCB-only strategy. The NATURE trial was a prospective, multicentre, randomised study conducted at 19 Japanese centres. Patients with de novo coronary lesions suitable for a DCB-only strategy were randomised (1:1) to lesion preparation with CB or SB. Post-predilatation assessment included coronary angiography, intravascular ultrasound (IVUS), and fractional flow reserve (FFR). The primary endpoint was optimal lesion preparation, defined as the simultaneous presence of: (1) no flow-limiting dissection, (2) residual diameter stenosis ≤ 30% by quantitative coronary angiography, and (3) FFR > 0.80. Among 201 patients included in the intention-to-treat population, optimal lesion preparation was achieved in 35.6% of the CB group and 30.0% of the SB group (adjusted risk ratio 1.19, 95% confidence interval 0.87–1.65; p = 0.28). Avoidance of flow-limiting dissection was high in both groups (98.0% vs 97.0%). CB predilatation resulted in lower residual diameter stenosis (30.8 ± 11.8% vs 34.5 ± 13.3%; p = 0.04) and less acute recoil (1.18 ± 0.36 vs 1.31 ± 0.50 mm; p = 0.03). Trends towards larger lumen dimensions on IVUS were also observed with CB. In patients undergoing DCB-only PCI for de novo coronary lesions, CB predilatation provided modest angiographic advantages compared with SB but did not significantly increase the rate of optimal lesion preparation. Optimal lesion preparation is essential for successful drug-coated balloon (DCB) therapy because DCBs do not provide mechanical scaffolding to maintain vessel patency. In this multicentre randomised trial, cutting balloon predilatation resulted in greater acute luminal expansion and less recoil than standard balloon predilatation, although it did not significantly increase the overall rate of optimal lesion preparation defined by angiographic and physiological criteria. These findings suggest that cutting balloons may offer modest mechanical advantages during lesion preparation in DCB-only PCI. However, the clinical significance of these acute angiographic advantages requires confirmation in larger trials and through longer-term follow-up. Graphical Abstract This central illustration summarises the study design, procedural workflow, and key findings of the NATURE trial. Patients with de novo coronary lesions were randomised to lesion preparation with a cutting balloon or a standard balloon before a drug-coated balloon (DCB)–only strategy. Multimodality assessments using quantitative coronary angiography (QCA) and fractional flow reserve (FFR) were performed serially from pre–percutaneous coronary intervention through post-predilatation and post-DCB treatment, and intravascular ultrasound (IVUS) was performed after predilatation. The primary endpoint—achievement of optimal lesion preparation defined as the absence of flow-limiting dissection, residual diameter stenosis ≤ 30%, and FFR > 0.80—was achieved in 35.6% of patients in the cutting balloon group and 30.0% in the standard balloon group. Cutting balloon use was associated with less aggressive predilatation and more favorable acute angiographic outcomes, including greater minimum lumen diameter and lower acute recoil, whereas the overall achievement of optimal lesion preparation and the DCB-only strategy without bailout stenting was comparable between the groups. DCB = drug-coated balloon; FFR = fractional flow reserve; IVUS = intravascular ultrasound; MLD = minimum lumen diameter; MLA = minimum lumen area; PCI = percutaneous coronary intervention; QCA = quantitative coronary angiography.