Local Delivery of Enoxaparin to Decrease Restenosis After Stenting: Results of Initial Multicenter Trial

Abstract

This is the first prospective randomized trial in which the local delivery of a drug, enoxaparin, resulted in significant reduction in late luminal loss and restenosis after stent implantation in de novo coronary lesions.

Adeno-Associated Viral Vectors Based on Serotype 3b Use Components of the Fibroblast Growth Factor Receptor Signaling Complex for Efficient Transduction

“…One of the primary causes of vein graft failure is vascular smooth muscle cell (VSMC) proliferation. Studies in cell culture and animal models have shown that heparin is capable of inhibiting vascular smooth muscle proliferation, and human clinical trials have suggested that low molecular weight forms of heparin can inhibit intimal hyperplasia associated with vein graft failure (Kiesz et al, 2001;Wilensky et al, 2000). Perhaps an SASTG vector codelivered with heparin may synergistically confer higher levels of gene expression and prevent initial onset of intimal hyperplasia.…”

Targeted Treatments for Restenosis and Vein Graft Disease

“…Restenosis has been characterised as a return to ≥70% stenosis and loss of ≥50% of initial gain; the loss of ≥0.7 mm of the vessel diameter; ≥50% stenosis; loss of 50% of initial gain; 50-75% stenosis; % loss of initial gain; change from <50% to ≥50% stenosis; ≥50% stenosis and >50% of initial gain or >20% luminal diameter; or the recurrence of clinical symptoms or adverse events. Binary stenosis divides the cohort of patients (or blockages) into those with <50% stenosis and those with ≥50% stenosis (regardless of initial gain) [5,8,14,21,22,46,53,[73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88]. Vein graft disease is usually measured as % stenosis.…”

“…Clinically, systemic high dose LMWHs (with or without pretreatment) may improve patency in peripheral bypass grafts [39], but may not prevent restenosis [74,78,80,81]. Further clinical studies of locally delivered LMWH pinned in place with a stent after drug administration showed a decreased the degree of restenosis [82], but a study on "unsecured" LMWH delivered in a similar manner found that the drug was not effective [164]. It may be that LMWH needs to be held in place in order to act as an antirestenotic agent.…”

“…Therapies that require systemic administration have been found wanting, and this has led to considerable interest in developing new delivery systems and improving established targeting techniques. It is also becoming apparent that antirestenotic agents must not just be locally delivered to the appropriate site, but also be supported by some kind of mechanism to hold it in place, whether mechanical as in stents [23,82,100], or physiological, as in the binding of antibodies to fibrin formed at the angioplasty site [106,107] or incorporation into the artery wall [123,288] for a sufficient time. However, restenosis and vein graft disease are multifaceted diseases, and administration of a single drug directed at a single aspect of treatment may not be effective at limiting vessel closure [12], particularly if administered for a short time.…”

Transplant Renal Artery Stenosis

“…Hung Su reported on 9 cases of TRAS treated with primary stenting after PTA without any evidence of any recurrence after a 4 year follow-up [13]. A novel development to reduce stent occlusion was the introduction of stents that release agents like rapamycin and enoxaparin locally to inhibit intimal hyperplasia [36].…”