Colchicine and antineoplastic therapy for the prevention of restenosis after percutaneous coronary interventions.
The complexity of the events that culminate in intimal proliferation after arterial injury and similarities between this response and benign neoplasia suggest that conventional medical therapies will continue to be unsuccessful in preventing recurrent stenosis after percutaneous coronary revascularization. By preventing cell division after smooth muscle cell activation, antimitogenic therapy may inhibit the final common pathway in this complex chain of events and offset the apparent loss of local growth control. Colchicine, which causes metaphase arrest of cell division, has been shown in experimental studies to decrease the extent of atheromatous plaque formation and reduce the severity of arterial restenosis after balloon angioplasty. However, preliminary results from a randomized placebo-controlled clinical trial suggest that low dose colchicine (0.6 mg twice a day orally) does not prevent restenosis. The use of more potent antineoplastic agents is limited by the potential for life-threatening side effects. It is possible that these adverse effects can be averted by using novel drug delivery systems to administer antimitogenic therapy locally at the site of arterial injury or by using low dose synergistic combinations of antiproliferative agents. This review examines the potential role of antimitogenic therapy in the prevention of restenosis after coronary interventions and considers the possibility of an overlap of the therapeutic realms of interventional cardiology and medical oncology.
Muller
D W
DW
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0022.
Ellis
S G
SG
Topol
E J
EJ
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002986:Clinical Trials as Topic; D003078:Colchicine / Q000494:pharmacology / Q000627:therapeutic use*; D003327:Coronary Disease / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D012008:Recurrence
D000970:Antineoplastic Agents; D003078:Colchicine