Key result
Nine classes of pharmacologic agents inhibited intimal proliferation in >50 animal studies, but none reproducibly reduced human coronary restenosis due to interspecies differences.
Why the study?
Although experimental animal studies have suggested that at least nine pharmacologic classes inhibit the intimal proliferative response to arterial injury, no pharmacologic intervention has reproducibly reduced restenosis after coronary balloon angioplasty in humans. It remained unclear why animal models lacked specificity and which model most reliably predicts human efficacy.
Significant interspecies and intraspecies differences in neointimal thickening among experimental animal models help explain why pharmacologic agents that inhibit arterial injury responses in animals have failed to reproducibly reduce restenosis after coronary balloon angioplasty in humans.
Animal restenosis models are hypothesis-generating; human studies required before any translational relevance.
The study of potentially effective drug therapies and mechanical devices for the prevention of restenosis after percutaneous coronary revascularization has relied heavily on the use of experimental animal models. To date, greater than 50 experimental studies have been reported and have suggested that at least nine different classes of pharmacologic agents inhibit the intimal proliferative response to arterial injury. However, no pharmacologic intervention has yet been shown to reproducibly reduce the incidence of restenosis after coronary balloon angioplasty in humans. To identify the reasons for the apparent nonspecificity of the animal models and to determine which model should most reliably predict the efficacy of individual therapies in humans, the distinguishing characteristics of the experimental models were compared. Particular attention was paid to the size and morphologic structure of the treated artery, the susceptibility of the species to spontaneous and diet-induced arterial disease, the nature of the stimulus to intimal proliferation and several practical and logistic considerations. Finally, the reported efficacies of specific drug therapies in the respective animal models and in humans were compared. This review suggests that significant interspecies and occasionally intraspecies differences do exist among the respective animal models, particularly in the extent and composition of the neointimal thickening.(ABSTRACT TRUNCATED AT 250 WORDS)
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Muller et al. (1992) conducted a review in Coronary artery restenosis after percutaneous coronary revascularization. Pharmacologic agents (at least 9 classes) and mechanical devices vs. Different animal models vs. humans was evaluated on Prevention of restenosis / inhibition of intimal proliferative response to arterial injury. Nine classes of pharmacologic agents inhibited intimal proliferation in >50 animal studies, but none reproducibly reduced human coronary restenosis due to interspecies differences.
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