Local delivery of nadroparin for the prevention of neointimal hyperplasia following stent implantation: results of the IMPRESS trial. A multicentre, randomized, clinical, angiographic and intravascular ultrasound study.

BACKGROUND: We hypothesized that intramural delivery of nadroparin, a low molecular weight heparin, would prevent in-stent restenosis by inhibiting neointimal hyperplasia in an angioplasty model free of arterial remodelling. METHODS AND RESULTS: In a prospective randomized multicentre trial, 250 patients submitted to balloon angioplasty followed by stent implantation were randomized into control group (no local drug delivery) or intramural delivery of nadroparin (2 ml of 2500 anti-Xa-units/ml with a microporous catheter). An ancillary intravascular ultrasound substudy was performed to supplement angiographic data with specific measurements of in-stent neointimal hyperplasia. The primary end-point was the late loss in minimal luminal diameter on the 6 month follow-up angiogram. Secondary end-points included feasibility and safety of local nadroparin delivery, and major adverse cardiac events at 8 weeks and 6 months follow-up. Local delivery of nadroparin was successful in 124 patients (99.2% success rate) and was not associated with an increase in stent thrombosis, coronary artery dissection, side branch occlusion, distal embolization or abrupt arterial closure. At angiographic follow-up, the late loss in lumen diameter was 0.84 +/- 0.62 mm in the control group compared to 0.88 +/- 0.63 mm in the nadroparin group (P=0.56). Angiographic restenosis rate (defined as a >50% diameter stenosis) did not differ in the control group (20%) compared to the nadroparin group (24%). The average area of neointimal tissue within the stent was 2.86 +/- 0.64 mm(2) vs 2.90 +/- 0.53 mm(2) (P=0.57), control vs nadroparin groups. There was no difference in major adverse cardiac events at any time (88.8% vs 89.6% event free survival at 6 months, control vs nadroparin). CONCLUSION: Intramural delivery of nadroparin with a microporous catheter after stent deployment was feasible and safe but had no effect in reducing restenosis or the occurrence of major adverse clinical events over 6 months.