Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty

Abstract

Colchicine, an antimitogenic agent, has shown promise in preventing restenosis after coronary angioplasty in experimental animal models. A prospective trial was conducted involving 197 patients randomized in a 2:1 fashion to treatment with oral colchicine, 0.6 mg twice daily (130 patients), or placebo (67 patients) for 6 months after elective coronary angioplasty. Treatment in all patients began between 12 h before angioplasty and 24 h after angioplasty. Compliance monitoring revealed that 96% of all prescribed pills were ingested. Demographic characteristics were similar in colchicine- and placebo-treated groups. A mean of 2.7 lesions/patient were dilated. Side effects resulted in a 6.9% dropout rate in the colchicine-treated patients. Complete quantitative angiographic follow-up was obtained in 145 patients (74%) with 393 dilated lesions. Quantitative angiographic measurements were obtained in two orthogonal views at baseline before angioplasty and immediately and at 6 months after angioplasty. The quantitative mean lumen diameter stenosis before angioplasty was 67% both in the 152 lesions in the placebo-treated group and in the 241 lesions in the colchicine-treated group; this value was reduced to 24% immediately after angioplasty in the lesions in both treatment groups. At the 6-month angiogram, lesions had restenosed to 47% lumen diameter narrowing in the placebo-treated group compared with 46% in the colchicine-treated group (p = NS). Forty-one percent of colchicine-treated patients developed restenosis in at least one lesion compared with 45% of the placebo-treated group (p = NS). In conclusion, colchicine was ineffective for preventing restenosis after coronary angioplasty.

Gamma irradiation inhibits neointimal hyperplasia in rats after arterial injury.

“…13 A variety of pharmacologic means have been tested in an attempt to control SMC proliferation after vascular injury. Clinical trials of drugs including antiplatelet agents, 1415 anticoagulants, 16 corticosteroids, 17 calcium channel blocking agents, 18 and colchicine 19 have proven unsuccessful in reducing restenosis rates. Heparin has been consistently successful in controlling SMC proliferation in experimental models, both systemically administered 20 - 21 and locally applied to the vessel.…”

Increased Expression of Membrane-Type Matrix Metalloproteinase and Preferential Localization of Matrix Metalloproteinase-2 to the Neointima of Balloon-Injured Rat Carotid Arteries

“…[1][2][3][4] Numerous attempts to modify the fibroproliferative response to arterial injury, either through pharmacological interventions or mechanical devices, have met with very limited success. [5][6][7][8][9] This failure reflects, in part, the complexity of the pathophysiological process of neointima formation after balloon injury and the difficulty in identifying the appropriate cellular or molecular target(s) for therapeutic intervention. 10 -12 An understanding of the events involved in ECM remodeling, which is required for VSMC migration and, possibly, proliferation, 13 may provide additional targets for modifying restenosis.…”

Targeted Treatments for Restenosis and Vein Graft Disease

“…Colchicine is quickly cleared after systemic administration, and this may account for its lack of clinical effect in clinical studies. There was a high patient drop-out rate in the clinical trials, due to adverse side effects (despite a reduction in dose from that found optimal in animal studies) [23,73,76,229,231]. While an infusion of colchicine via a balloon catheter did not have a long dwell time in rabbit artery walls, its retention was improved by containment within microparticles, resulting in a decrease in neointimal thickening [232].…”

“…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.…”