Microcrystalline paclitaxel-coated balloon for revascularization of femoropopliteal artery disease: Three-year outcomes of the randomized BIOPAC trial.

The aim of the BIOPAC trial was to determine long-term safety and efficacy of a novel microcrystalline paclitaxel-coated balloon (mcPCB) with a biocompatible polymer as an excipient in the treatment of occlusive femoropopliteal lesions. In this first-in-human prospective controlled randomized trial, 66 patients with femoropopliteal, symptomatic (Rutherford stages 2B to 5) occlusive arterial disease were randomized to either mcPCB (study group) or POBA (plain old balloon angioplasty) (control group) on a 1:1 basis. Late lumen loss (LLL) at 6 months was the primary endpoint of the study and serious adverse events (SAE: death, amputation, repeated revascularization) were considered a composite secondary endpoint. Routine angiography was scheduled for all study subjects at 6-month follow-up; outpatient appointments were scheduled at 12 and 36 months after intervention. At 6 months, the LLL was 63% lower in the mcPCB group compared to the POBA group (0.52 ± 1.2 vs 1.39 ± 1.1 mm; psup < 0.01). Binary restenosis occurred in 23% vs 52% of patients (p = 0.02). At 3 years, the prevalence of SAE was significantly lower in the mcPCB group (33.3 vs 63.3%; p = 0.02), which mainly resulted from a twofold reduction in target vessel revascularization rate (28.6 vs 59.3%; p = 0.02). The difference in mortality was nonsignificant (7.4 vs 14.3%; p = 0.42). Patients with mcPCB were less symptomatic and less likely to adhere to secondary prevention measures. In this pivotal trial, a novel mcPCB proved superior to POBA concerning LLL at 6-month follow-up, and SAE at 12 months. This result was sustained up to 3 years. There was no difference between groups regarding mortality. ClinicalTrials.gov Identifier: NCT02145065.

Local intravascular delivery of low-density-lipoprotein cholesterol corresponds with increased intimal thickening in a healthy porcine coronary model. A prelude to development of a model of atherosclerosis.

INTRODUCTION: Preclinical, vascular response studies are limited due to lack of underlying disease. The available cholesterol-diet-based and genetic atherosclerotic models are not satisfactory due to long breeding, unpredictable lesion formation, low plaque volume and degree of stenosis. AIM: To evaluate the vascular response to local, intramural delivery of human, highly atherogenic lipids into healthy domestic swine (DS) coronary arteries. MATERIAL AND METHODS: A total of 24 coronary artery segments of 10 DS were enrolled. Following balloon injury (plain old balloon angioplasty - POBA), segments were assigned to local delivery of 2 ml of human LDL from apheresis (400 mg/dl, n = 9), 0.9% NaCl (control, n = 7) or to POBA alone. The solutions were infused with a modified, triple micro-needle catheter into the vessel wall. After 28 days, optical coherence tomography (OCT), virtual histology IVUS (VH-IVUS) and near-infra-red spectroscopy (NIRS) were performed. Following euthanasia, vessel segments were harvested for pathological evaluation. RESULTS: At 28 days the % area stenosis in OCT was highest in the LDL group (23.6 ±13 vs. 10.8 ±7 vs. 8.1 ±7%; p = 0.02). The presence of necrotic core (LDL: 55.5%, control: 37.5% and POBA: 42.8%; p = 0.77) and dense calcium (LDL: 33.3%, control: 28.5%, POBA: 37.5%; p = 0.94) in VH-IVUS were comparable between groups. The lipid core burden index in NIRS was negative in all cases. In pathology, the injury was comparable between groups (LDL: 1.6 ±0.4, control: 1.7 ±0.8, POBA: 1.7; p = 0.8) and specimens showed no signs of necrotic or lipid core. The tissue consisted of smooth muscle cells (SMC)/proteoglycan-rich lesions and inflammatory cells. CONCLUSIONS: Local delivery of saturated human LDL into the coronary artery wall was feasible and resulted in a higher degree of stenosis caused by intimal thickening. A discrepancy between histopathological findings and virtual histology intravascular ultrasound (VH-IVUS) was also noted.