Use of locally delivered conventional drug therapies.
Coronary artery restenosis remains the major limitation of balloon angioplasty and occurs in 30-50% of initially successful procedures. Our current understanding of pathophysiology of restenosis suggests that it involves three inter-related phases; (1) acute effects of thrombosis, (2) neointimal proliferation, and (3) acute recoil and chronic remodelling. In an attempt to prevent vessel restenosis both systemic and site-specific pharmacotherapy have been investigated. Although successful in animal models, systemically administered pharmacological agents for the prevention of restenosis in humans have not been effective. The local administration of compounds such as heparin, anti-thrombin agents, colchicine, angiopeptin, antineoplastic agents, calcium antagonists, nitrates, forskolin, cytochalasin B, protein kinase inhibitors and dexamethasone have been shown to reduce neointimal formation in animal models of restenosis. Clinical trials have demonstrated the feasibility of the local administration of heparin using both InfusaSleeve and Dispatch drug delivery catheters. Preliminary results on long-term prevention of restenosis by heparin appear promising using the Dispatch delivery device. In addition, a multicentre trial investigating the effectiveness of cytochalasin B delivered using the Microporous Infusion Catheter for the prevention of restenosis is currently underway. Rapid progress in our understanding of the complex pathophysiology of restenosis and the development of more effective pharmacological agents and atraumatic site specific delivery modalities ensure a promising future for local delivery strategies.
Camenzind
E
E
Cathelerization Laboratory, Thoraxcenter, Erasmus University, Rotterdam, The Netherlands.
Kutryk
M J
MJ
Serruys
P W
PW
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use; D002404:Catheterization; D003327:Coronary Disease / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007261:Infusions, Intra-Arterial / Q000379:methods*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D055502:Secondary Prevention; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use
D000925:Anticoagulants; D000970:Antineoplastic Agents; D000991:Antithrombins; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents