Abstract 3036: Effect of High-Dose Quinapril on In-Stent Restenosis Rate and Association with Apoptosis Indices
The regulation of apoptotic processes has been implicated in the evolution of restenosis after percutaneous coronary interventions (PCI) and angiotensin II has been shown to increase proliferation of vascular smooth muscle cells, while its blockade could result in increased apoptosis of the cellular components of restenotic plaques. We studied 60 symptomatic patients with significant obstructive (> 70%) lesions of the left anterior descending artery (LAD), submitted to elective PCI. The patients were randomly assigned to receive 40 mg of quinapril qd, starting one week before PCI and continued for 6 months, or placebo, in addition to standard treatment. Anti-hypertensive treatment (with the exception of angiotensin converting enzyme [ACE] and angiotensin receptor inhibitors) was administered as required to maintain desired blood pressure levels in both groups. Coronary angiography (CAG) was performed 6 months after the PCI to assess restenosis (at least 50% of lumen diameter). Plasma levels of apoptotic mediators soluble Fas and Fas ligand were measured (ELISA) in blood samples drawn during catheterization from the LAD artery (at the time of PCI and 6 months later). Restenosis rates in the quinapril-treated and in the control group were 21.2% and 29.7% respectively (p < 0.05, odds ratio 1.84, 95% CI 1.38 –2.5) and the late loss in minimum lumen diameter was 0.88 ± 0.4 mm and 1,05 ± 0.6 mm, respectively (p = 0.001). Plasma concentrations of Fas and Fas ligand in the LAD blood were significantly increased in the quinapril group at the 6-month CAG compared to baseline (4.8 ± 0.3 ng/ml vs 2.9± ng/ml for Fas and 54.4±3.3 pg/ml vs 32.5±1.9 pg/ml for Fas ligand, respectively), while no significant difference was observed in the control group. We report a potential effect of a relatively high dose of the ACE inhibitor quinapril on apoptotic markers in blood drawn form the LAD, which may be linked to the observed difference of in-stent restenosis, following PCI in the LAD. Increased apoptotic activity may be associated with inhibition of the neo-intimal hyperplasia and the overall atherogenic process, resulting in reduction of in-stent restenosis.