Results of a Meta-Analysis of Trapidil, a PDGF Inhibitor Ñ A Sufficient Reason for a Second Look to the Pharmacological Approach to Restenosis

Abstract

Restenosis in 30%Ð40% of patients remains the major limitation to the long-term success of balloon angioplasty (PTCA) in patients with coronary artery disease. So far, only coronary stent implantation has established its role as an effective strategy to prevent restenosis after PTCA. In contrast to numerous pharmacological strategies that all have failed to demonstrate a convincing reduction in the rate of restenosis, trapidil, a PDGF inhibitor, has shown promising and conclusive results in animal models as well as in three human trials published between 1992 and 1994. Although the results of the human trials showed trapidil to be capable of reducing restenosis after PTCA by 40%Ð53% compared to control patients, the compound is not well known and little used in interventional cardiology. Possible explanations for this situation may include trapidilÕs non-availability in the United States and most European countries, the small number of trapidil trials and treated patients, as well as a probable perception of the medical community that a pharmacological approach to restenosis prevention is unlikely to work. Additionally, clinical expert behavior has often shown not to be synchronized with accumulating evidence of efficacy. The results of this meta-analysis, however, demonstrate trapidilÕs efficacy. The rate of per-patient restenosis in the trapidil group was more than halved as compared to controls (odds ratio 0.44, 95% confidence interval 0.29Ð0.66). Tolerability with trapidil was good, and the rare adverse events observed included gastric intolerance, thrombocytopenia, headache, and increased serum AST and ALT levels which were transient or subsided with cessation of treatment.