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CLINICAL STUDIES

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

Kenneth G. Lehmann, MD, FACC^{* b}, Jeffrey J. Popma, MD, FACC^{* b}, Jeffrey A. Werner, MD, FACC^{* b}, Alexandra J. Lansky, MD^{* b} and Robert L. Wilensky, MD, FACC^{* b}

^* Division of Cardiology, University of Washington School of Medicine, Veterans Affairs Puget Sound Health Care System and Providence Health Group, Seattle, Washington, USA
^b the Washington Hospital Center, Washington, DC, USA
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

Manuscript received December 31, 1998; revised manuscript received October 14, 1999, accepted November 18, 1999.

Reprint requests and correspondence: Dr. Kenneth G. Lehmann, Section of Cardiology (111C), VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, Washington 98108

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.

Abbreviations and Acronyms   AHA = American Heart Association   ACC = American College of Cardiology   CAAS = coronary angiography analysis system   MLD = minimal lumen diameter   NHLBI = National Heart, Lung and Blood Institute   RD = reference diameter   PTCA = percutaneous transluminal coronary angioplasty

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