Low molecular weight heparin in prevention of restenosis after angioplasty. Results of Enoxaparin Restenosis (ERA) Trial.

Faxon, David P.; Spiro, Theodore E.; Minor, Steven T.; Côté, Gilles; Douglas, John S.; Gottlieb, Ronald H.; Califf, Robert M.; Dorosti, Khosrow; Topol, Eric J.; Gordon, John B.

doi:10.1161/01.cir.90.2.908

Cited by 164 publications

(71 citation statements)

References 32 publications

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“…19 Some agents that tested positive and then failed to show benefit in the clinic include heparin, calcium-channel blockers, antiplatelet drugs and angiotensin-converting enzyme (ACE) inhibitors. 19,[62][63][64][65][66][67] When tested in the baboon model, ACE inhibitors did not decrease intimal thickening after balloon angioplasty or endarterectomy. 23 Heparin, the only other of these agents tested in baboons, did not inhibit lesion formation at the usual antithrombotic doses that were effective in the rat.…”

Section: Discussionmentioning

confidence: 99%

The Role of Alpha and Beta Platelet-Derived Growth Factor Receptor in the Vascular Response to Injury in Nonhuman Primates

Giese

Marijianowski²,

McCook³

et al. 1999

ATVB

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Abstract-Restenosis remains a significant clinical problem associated with mechanical interventional procedures for arterial revascularization or repair, including coronary angioplasty and stenting. Studies with rodents have established that platelet-derived growth factor (PDGF), a potent chemotactic and mitogenic agent for vascular smooth muscle cells, is a key mediator of lesion formation after vascular injury. To further explore this hypothesis in a more clinically relevant model, neutralizing monoclonal antibodies (mAbs) were used to examine the effect of selective inhibition of alpha or beta PDGF receptor (PDGFR) on neointima formation in nonhuman primates. Carotid arteries were injured by surgical endarterectomy and femoral arteries by balloon catheter dilatation. Immunostaining revealed that both injuries induced cell proliferation and the upregulation of beta PDGFR but not alpha PDGFR. By 7 days after injury, beta PDGFR staining was limited to the luminal region of the media, the small areas of neointima, and the adventitia. Nearly all bromodeoxyuridine-positive cells were found in these regions as well. After 30 days, a concentric neointima that stained strongly for beta PDGFR had formed in the carotid and femoral arteries. Treatment of baboons with anti-beta PDGFR mAb 2A1E2 for 6 days after injury reduced the carotid artery and femoral artery lesion sizes by 37% (PϽ0.05) and 48% (PϽ0.005), respectively, when measured at 30 days. Under the same conditions, treatment with anti-alpha PDGFR mAb 2H7C5 had no effect. These findings suggest that PDGF mediates neointima formation through the beta PDGFR, and that antagonism of this pathway may be a promising therapeutic strategy for reducing clinical restenosis.

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Section: Discussionmentioning

confidence: 99%

The Role of Alpha and Beta Platelet-Derived Growth Factor Receptor in the Vascular Response to Injury in Nonhuman Primates

Giese

Marijianowski²,

McCook³

et al. 1999

ATVB

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“…Heparin and aspirin have not reduced restenosis rates in nonhuman primates 44 or in human beings, 45 but potential combined effects with c7E3 may need to be considered. Our treatment protocol also differed from dosing strategies of other ␤3 inhibitors that are effective at inhibiting intimal hyperplasia in nonprimate animal models.…”

Section: ␤3 Integrins and Restenosis: Contrasts Among The Current Stumentioning

confidence: 99%

Effects of β3-Integrin Blockade (c7E3) on the Response to Angioplasty and Intra-Arterial Stenting in Atherosclerotic Nonhuman Primates

Deitch

Williams

Adams

et al. 1998

ATVB

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Abstract-Because the ␤3-antagonist abciximab (c7E3 Fab) has significantly improved late outcomes after coronary angioplasty, the ␤3 integrins have been implicated in the arterial response to injury. However, the mechanisms underlying this benefit are unknown. The observation that c7E3 binds ␤3 integrins on vascular cells (␣v␤3) with affinity equal to that for the platelet glycoprotein IIb/IIIa integrin has led to the hypothesis that c7E3 may act directly on the artery wall to prevent restenosis after angioplasty. To test this hypothesis, we studied the effects of c7E3 on structural changes within the artery wall after angioplasty or stent angioplasty in 23 male cynomolgus monkeys with established atherosclerosis. Animals were randomly assigned to receive either a bolus of c7E3 (0.4 mg/kg IV, nϭ11) followed by a 48-hour infusion (0.2 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) or an equal volume of vehicle (nϭ12). Animals received weight-adjusted aspirin and heparin and then underwent unilateral iliac artery experimental angioplasty and subclavian artery stent angioplasty (Palmaz). Iliac artery lumen diameter (LD) was determined by angiography at baseline (LD Pre ), after angioplasty (LD Post ), and 35 days later (LD Day35 ). Arteries were then fixed by perfusion and removed for analysis. Lumen, intima, media, and external elastic lamina (EEL) areas were measured in iliac artery cross sections. Values from each injured iliac artery were normalized to the contralateral uninjured iliac artery to control for interanimal variability in baseline artery size and atherosclerosis extent. Intimal area was also measured in subclavian stent cross sections. c7E3 blocked platelet aggregation and prolonged the bleeding time from 2.8Ϯ1.1 to 19.8Ϯ2.5 minutes, PϽ0.001. Experimental angioplasty increased LD Post an average of 28%, and the initial gain was similar in both groups (PϭNS). Despite an anti-platelet effect, c7E3 did not inhibit iliac lumen narrowing (LD Day35

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“…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.…”

Section: What Are Restenosis and Vein Graft Disease?mentioning

confidence: 99%

Targeted Treatments for Restenosis and Vein Graft Disease

Thomas

2012

ISRN Vascular Medicine

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Surgery to restore blood flow in arteries blocked by atherosclerotic plaque is a common treatment in cardiovascular disease. Longterm complications of surgical treatment are vein graft disease and restenosis, a renarrowing of the blood vessel after bypass or removal of the culprit atherosclerotic plaque. Attempts to prevent or treat these complications by systemic pharmacological approaches have been largely unsuccessful in the clinic. This has led to an interest in developing targeted or locally delivered strategies. This paper discusses many of the various site-delivered therapies that are under examination as potential antirestenotic and antivein graft disease agents (including antithrombotic, antiproliferative, and anti-inflammatory agents) and why many therapies developed in animal models fail in clinical trials. Techniques of targeted delivery (including stents, "magic bullets," and adventitial delivery) and delivery systems (including nanoparticles and the use of gene therapy) are also discussed.

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Low molecular weight heparin in prevention of restenosis after angioplasty. Results of Enoxaparin Restenosis (ERA) Trial.

Abstract: Enoxaparin (40 mg/d SC for 1 month) following successful angioplasty did not reduce the incidence of angiographic restenosis or the occurrence of clinical events over 6 months. The treatment was well tolerated, although in-hospital minor bleeding was more common with active treatment.

Cited by 164 publications

References 32 publications

The Role of Alpha and Beta Platelet-Derived Growth Factor Receptor in the Vascular Response to Injury in Nonhuman Primates

The Role of Alpha and Beta Platelet-Derived Growth Factor Receptor in the Vascular Response to Injury in Nonhuman Primates

Effects of β3-Integrin Blockade (c7E3) on the Response to Angioplasty and Intra-Arterial Stenting in Atherosclerotic Nonhuman Primates

Targeted Treatments for Restenosis and Vein Graft Disease

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