Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans.

OBJECTIVES This study sought to determine the safety, feasibility and outcome of local delivery of cytochalasin B at the site of coronary angioplasty. BACKGROUND Previous failures in the pharmacologic prevention of restenosis may have been related to inadequate dosing at the angioplasty site as a result of systemic drug administration. Alternatively, although previous experimental protocols have typically targeted control of excess tissue growth (intimal hyperplasia), it now appears that overall arterial constriction (vascular remodeling) is the major contributor to late lumen loss. Cytochalasin B inhibits the polymerization of actin and has proved to be a potent inhibitor of vascular remodeling in animal models. METHODS In this phase I, multicenter, randomized, controlled trial, cytochalasin B (or matching placebo) was administered to the site of a successful balloon angioplasty using a microporous local delivery infusion balloon. RESULTS The rate of drug delivery at a constant infusion pressure varied significantly from patient to patient (range 1.7 to 20.2 ml/min), perhaps related to a variable constricting effect of the atherosclerotic plaque on the infusion balloon. The minimal stenosis diameter after the procedure was slightly better in the active drug group (1.86 +/- 0.44 vs. 1.49 +/- 0.63 mm, p < 0.03), but this difference was not seen at four to six weeks. Although the study was not powered for clinical outcomes (n = 43), the combined end point (death, nonfatal infarction or repeat revascularization) was encountered in 20% of the patients receiving cytochalasin B and in 38% of the patients receiving placebo. Clinical restenosis occurred in 18% of the treatment group and 22% of the placebo group. There were no significant differences between groups in biochemical or electrocardiographic variables. CONCLUSIONS Cytochalasin B can be safely administered by local delivery after successful coronary angioplasty and warrants further study of its efficacy in reducing restenosis.