imidapril and Coronary-Disease

Angiotensin-converting enzyme (ACE) inhibitors are reported to prevent neointimal formation after balloon injury in animal models, but in most prospective studies in humans, ACE inhibitors failed to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA). The ACE genotype assigned by an insertion/deletion (I/D) polymorphism is known to affect the potency of ACE inhibitors in several renal diseases. The authors attempted to clarify whether the effect of ACE inhibitors on restenosis might be modified by the ACE genotype. A total of 126 patients was randomly and prospectively assigned to the control group and the imidapril group. In the imidapril group, patients received 5 mg imidapril daily, starting 1 day before PTCA and continuing for 3 to 6 months. Forty-six control (65 vessels) and 32 imidapril patients (43 vessels) completed the study. The minimal lumen diameter before and after the procedure did not differ significantly among the groups with the three genotypes (II, ID, and DD) in both the control and imidapril groups. Late luminal loss during the follow-up period was not related to the ACE genotype in the control group but was significantly related in the imidapril group (II, 0.63+/- 0.19 mm; ID + DD, 1.12+/-0.14 mm, p<0.05). Furthermore, in the II genotype, imidapril significantly reduced late loss and restenosis rate as defined by most of the frequently used definitions. In conclusion the ACE I/D polymorphism may influence the effect of ACE inhibitors in preventing restenosis after PTCA.

Topics: Aged; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Coronary Angiography; Coronary Disease; Female; Follow-Up Studies; Gene Deletion; Gene Expression Regulation, Enzymologic; Genotype; Humans; Hyperplasia; Imidazoles; Imidazolidines; Male; Middle Aged; Mutagenesis, Insertional; Peptidyl-Dipeptidase A; Pharmacogenetics; Polymorphism, Genetic; Prospective Studies; Recurrence; Tunica Intima

For this study, we used (NZW x BXSB)F1 male mice as a model of myocardial infarction. The animals were kept on water containing imidapril or enalapril at 60 mg/kg/day from 10 to 27 weeks of age. Imidapril and enalapril significantly reduced the blood pressure. Imidapril reduced the mortality rate more significantly than enalapril did. In the second experiment where imidapril, enalapril and captopril were administered to the mice at 5 mg/kg/day, p.o., both imidapril and captopril significantly reduced the mortality, but enalapril did not. Blood pressure was slightly reduced by these ACE inhibitors. These data suggest that imidapril and captopril are efficacious for the treatment of myocardial infarction and blood pressure reduction hardly contributes to its mechanism of action.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Coronary Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Heart Rate; Imidazoles; Imidazolidines; Male; Mice; Mice, Inbred Strains; Myocardial Infarction