Effects of Combined Therapy with Ezetimibe Plus Simvastatin After Drug-Eluting Stent Implantation in a Porcine Coronary Restenosis Model

Abstract

The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin (E/S) after drug-eluting stent (DES) implantation in a porcine coronary restenosis model. Pigs were randomized into two groups in which the coronary arteries (23 pigs) had DES. Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Fifteen pigs were taken 10/20 mg of E/S and eight pigs were not taken E/S. Histopathologic analysis was assessed at 28 days after stenting. In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337±227 vs. 443±366 cells, P=0.292), but neointima area was significantly smaller (1.00±0.49 mm2 vs. 1.69±0.98 mm2, P=0.021) and percent area stenosis was significantly lower (23.3±10% vs. 39±19%, P=0.007) in E/S group compared with control group. There were no significant differences in fibrin score (1.99±0.79 vs. 1.81±0.88, P=0.49), endothelial score (1.75±0.66 vs. 1.80±0.59, P=0.79), and the percent of endothelium covered lumen (43±21% vs. 45±21%, P=0.84) between E/S group and control group. Combined therapy with ezetimibe and simvastatin inhibits neointimal hyperplasia, but does not inhibit inflammatory infiltration and arterial healing after DES implantation in a porcine coronary restenosis model.

Atorvastatin Accelerates Both Neointimal Coverage and Re-Endothelialization After Sirolimus-Eluting Stent Implantation in a Porcine Model

“…Cho et al found that combined therapy with ezetimibe and simvastatin further inhibited NIH in DES with no benefit for stent coverage after 28 days. 13 Neointima grows much more rapidly in the porcine model than in humans. 33 In the present study, neointimal coverage was almost complete in all 3 groups after 28 days.…”

“…Some previous studies have suggested that statins may assist re-endothelialization by enhancing the proliferation and migration of both mature endothelial cells and endothelial progenitor cells (EPCs). 9-12 However, other research shows inconsistent results 13 and the beneficial effects of statins on re-endothelialization after stent implantation are still controversial.…”

Effect of Pretreatment of Ezetimibe/Simvastatin on Arterial Healing and Endothelialization after Drug-Eluting Stent Implantation in a Porcine Coronary Restenosis Model

“… 27) In a porcine coronary restenosis model, combined therapy with ezetimibe and simvastatin inhibited neointimal hyperplasia after implantation of SES and PES but did not reduce inflammatory infiltration and arterial healing. 28) In a rabbit model of atherosclerosis induced by balloon de-endothelialization, ezetimibe reduced atherosclerotic lesion size and plaque inflammation when combined with simvastatin. 24) …”

Effectiveness of Drug-Eluting Stents versus Bare-Metal Stents in Large Coronary Arteries in Patients with Acute Myocardial Infarction

“…Furthermore, even though we used propensity score to adjust for treatment selection bias regarding the use of DES during PCI for acute MI, unmeasured confounders may have influenced the results. For instance, the use of long-term medical therapies that have potential efficacy of reducing restenosis might have affected the outcome ( 29 , 30 ). Finally, differences between the institutions involved in this research, although representative of the reality of the country's health system, may to some extent have introduced an unintentional bias.…”