Coronary heart disease is a kind of heart disease that is caused by atherosclerosis. The lipid deposition in the vessel wall results in occlusion of coronary artery and stenosis, which could induce myocardial ischemia and oxygen deficiency. Intervention therapies like percutaneous coronary intervention (PCI) and coronary stent improve myocardial perfusion using catheter angioplasty to reduce stenosis and occlusion of coronary artery lumen. Accordingly, intervention therapies are widely applied in clinic to treat ischemic cardiovascular disease, arterial intima hyperplasia and other heart diseases, which could save the patients' life rapidly and effectively. However, these interventions also damage the original endothelium, promote acute and subacute thrombosis and intimal hyperplasia, and thus induce in-stent restenosis (ISR) eventually. Studies indicated that the rapid reendothelialization of damaged section determined postoperative effects. In this review, reendothelialization of implants after intervention therapy is discussed, including the resource of cells contributed on injured artery, the influences of implanted stents on hemodynamic, and the effects of damaged degree on reendothelialization.
Angioplasty, Balloon, Coronary ; Cardiac Catheterization ; Coronary Artery Disease ; therapy ; Coronary Restenosis ; prevention & control ; Endothelium, Vascular ; pathology ; Humans ; Myocardial Ischemia ; prevention & control ; Stents ; Thrombosis ; prevention & control

Restenosis following vascular revascularization remains an important clinical problem. Local drug delivery which can provide enough drug concentration in the lesion location without causing adverse systemic effect is an excellent solution for this question. We conducted a systematic literatory search on PubMed and CKNI through May 2014. After reviewing all related papers, we provided a comprehensive overview of the available drugs and techniques for local drug delivery that have been developed to prevent restenosis after peripheral vascular interventions, including innovations that have been tested only in animals as well as those already approved for clinical use. In brief, anti-proliferative drugs such as paclitaxel and sirolimus are the most used and suitable drugs for local delivery system. Additionally, some promising drugs including anti-inflammatory drugs, antioxidant drugs and drugs inhibiting cell proliferation and migration are already being tested in pre-clinical trials or animal models. At the same time, intraluminal and extraluminal delivery devices have also got a rapid development during the past decades. The efficacy of drug-eluting stent, drug-eluting balloon, porous and microporous balloon and the most recent drug-eluting bioresobable scaffold for preventing of restenosis in peripheral vessels have been demonstrated in humans or in animals, some of them even have received the CE mark in Europe. Endovascular microinfusion catheter and drug-loaded perivascular wraps have only been tested in animal models, more researches are needed. With the development of pharmacology and bioengineering, great strides will be made in the prevention of restenosis in the near future.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; Antibiotics, Antineoplastic ; administration & dosage ; Arteries ; Coronary Restenosis ; prevention & control ; Drug Delivery Systems ; Drug-Eluting Stents ; Humans ; Myocardial Revascularization ; Paclitaxel ; Sirolimus

OBJECTIVETo discuss whether asiaticosides could effectively reduce the endothelial cell damage as a biochemical modulator, so as to further inhibit the post-stenting intima-media membrane hyperplasia.

METHODHuman aortic smooth muscle cells and aortic fibroblasts were selected and divided into the blank group, the rapamycin group and the asiaticoside group and the rapamycin and asiaticoside group. The expressions of muscle cells and fibroblasts TGF-beta1, Smad7 and I-collagen gene were determined by RT-PCR. The expression quantity of I-collagen protein was assayed by ELISA. The coefficient of drug interaction (CDI) between rapamycin and asiaticoside was calculated. Additionally, 16 Chinese mini-swines were randomly divided into group A and group B. One sirolimus drug-eluting stent of the same type was implanted after the high-pressure pre-expansion of anterior descending artery balloon. After the operation, the group A was intravenously injected with normal saline 30 mL x d(-1). Whereas the group B was intravenously injected with asiaticoside 30 mg x kg(-1) x d(-1)(diluted to 30 mL). The expressions of plasma vWF of the two groups were measured at the 7th and 14th days after the operation. At the 28th day after the operation, tissues of the stented vessel segments were sliced and stained to calculate the vessel area, inner stent area, lumen area and neointima area

RESULTCompared with the control group, the combination group showed significant up-regulation in smooth muscle cells and fibroblast Smad7 gene, down-regulation in TGF-beta, and obvious inhibition of I-collagen gene expression (P < 0.01). As for smooth muscle cells, there was no difference in the expression of I-collagen between the combination group and the rapamycin group, with CDI at 0. 83. As for fibroblasts, there was a significant difference in the expression of I-collagen between the combination group and the rapamycin group (P < 0.05), with CDI at 0.77. Plasma vWF of the group B was significantly lower than that of the group A (P < 0.05) at the 7th and 14th days after the operation. At the 28th day after the operation, no difference was observed in vessel area and stent area between the two groups. However, the lumen area in the group B was significantly larger than that of the group A(P < 0.05), and the neointima area of the group B was significantly smaller than that of the group A (P < 0.05).

CONCLUSIONAs an effective biochemical modulator for rapamycin, asiaticosides could inhibit TGF-beta expression, significantly decrease the synthesis and secretion of extracellular matrix, further inhibit the post-stenting intima-media membrane hyperplasia and reduce the endothelial cell damage by effectively up-regulate the expression of Smad7 protein.

Animals ; Collagen ; genetics ; metabolism ; Coronary Restenosis ; drug therapy ; prevention & control ; surgery ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hyperplasia ; drug therapy ; genetics ; metabolism ; prevention & control ; Smad7 Protein ; genetics ; metabolism ; Stents ; adverse effects ; Swine ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Triterpenes ; administration & dosage

BACKGROUNDDrug-eluting stents (DES) with durable polymer have significantly reduced restenosis and target vessel revascularization compared with bare metal stents. Durable polymer has been linked with persistent inflammation of vessel wall and delayed endothelial healing that may increase the risk of late and very late stent thrombosis. This study sought to evaluate the efficacy and safety of HELIOS completed biodegradable polymer sirolimus-eluting stent (SES) in de novo coronary lesions.

METHODSTotally, 287 patients with one or two de novo coronary lesions (lesion length ≤ 38 mm and reference vessel diameter 2.5-4.0 mm) were enrolled in the HOPE study, a prospective, multicenter, randomized, non-inferiority trial. Patients were randomized to treatment either with HELIOS completed biodegradable polymer SES (n = 142) or PARTNER durable polymer SES (n = 145). The primary endpoint was angiographic in-stent late lumen loss (LLL) at 9-month follow-up. The secondary endpoint included stent thrombosis and major adverse cardiac events including cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR).

RESULTSThe 9-month in-stent LLL in the HELIOS group was similar to the PARTNER group, (0.16 ± 0.22) mm vs. (0.19 ± 0.30) mm (P = 0.28). The difference and 95% confidence interval were -0.03 (-0.09, 0.04), and the P value for non-inferiority <0.01. Major adverse cardiovascular event (MACE) occurred in 7.9% vs. 8.2%, MI in 2.4% vs. 3.0%, TLR in 5.5% vs. 3.0%, and stent thrombosis in 0 vs. 1.5%; and events were comparable between the HELIOS group and PARTNER group at three-year follow-up (all P > 0.05). The three-year cardiac death was lower in the HELIOS group, but with no significant difference, 0 vs. 3.0% (P = 0.12).

CONCLUSIONSIn the HOPE trial, the novel completed biodegradable polymer SES HELIOS was non-inferior to the durable polymer SES PARTNER with respect to nine-month in-stent LLL in de novo coronary lesions. The incidence of other clinical endpoints was low for both of the stents in three-year follow-up.

Adult ; Aged ; Angiography ; Coronary Artery Disease ; surgery ; Coronary Restenosis ; prevention & control ; Drug-Eluting Stents ; Humans ; Middle Aged ; Percutaneous Coronary Intervention ; Polymers ; chemistry ; therapeutic use ; Sirolimus ; therapeutic use ; Titanium ; chemistry ; Treatment Outcome ; Young Adult

BACKGROUNDSirolimus-eluting stents (SES) are reported to be associated with reduced late lumen loss (LLL), resulting in less frequent restenosis when compared to bare-metal stent. The current study aimed to assess the difference in LLL between SES with biodegradable and with permanent polymer.

METHODSFrom March 2010 to June 2011, 300 consecutive patients having only biodegradable polymers or permanent polymer SES for all diseased vessels were included. Serial quantitative coronary analysis was performed on both the "in-stent" and "segment" area, including the stented segment, as well as both five mm margins proximal and distal to the stent. The primary endpoint was the LLL defined as the minimal lumen diameter (MLD) post-stenting minus the MLD at nine-month after the indexed procedure.

RESULTSLLL was comparable between the two stents. Importantly, LLL for the distal segment (median 0.05 mm, interquartile 0 to 0.09 mm) was less severe compared with in-stent (median 0.13 mm, interquartile 0.08 to 0.18 mm) and proximal segment LLL (median 0.12 mm, interquartile 0.06 to 0.14 mm, all P < 0.001). In general, the LLL was associated with the post-procedure MLD (b = 0.28, P = 0.002), hyperlipidemia (b = 0.14, P = 0.021), and calcified lesions (b = 0.58, P = 0.001). The R(2) and Radj of the multiple regression model were 0.651 and 0.625, respectively.

CONCLUSIONSSES with either biodegradable or permanent polymer had lower value of LLL. The small amount of LLL at the distal segment possibly contributed to the less distal edge stenosis.

Aged ; Aspirin ; therapeutic use ; Coronary Restenosis ; prevention & control ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Polymers ; chemistry ; Regression Analysis ; Sirolimus ; therapeutic use ; Ticlopidine ; analogs & derivatives ; therapeutic use

It is well known that beta-elemene is a broadly effective antitumor drug. In recent years, many studies suggested that beta-elemene also has potential value in the treatment of atherosclerosis and restenosis. In this paper, the effect of beta-elemene in inhibition of angiogenesis, inhibition of thrombus formation, improvement of hemorheology, protection against oxidative injuries, anti-inflammation and suppression of restenosis after percutaneous transluminal coronary angioplasty (PTCA) are summarized and reviewed.
Anti-Inflammatory Agents ; pharmacology ; Antioxidants ; pharmacology ; Atherosclerosis ; prevention & control ; Coronary Restenosis ; prevention & control ; Humans ; Sesquiterpenes ; pharmacology

We aimed comparing two-year clinical outcomes of the Everolimus-Eluting Promus and Paclitaxel-Eluting TAXUS Liberte stents used in routine clinical practice. Patients with objective evidence of ischemia and coronary artery disease eligible for PCI were prospectively randomized to everolimus-eluting stent (EES) or paclitaxel-eluting stent (PES) groups. The primary end-point was ischemia-driven target vessel revascularization (TVR) at 2 yr after intervention, and the secondary end-point was a major adverse cardiac event (MACE), such as death, myocardial infarction (MI), target lesion revascularization (TLR), TVR or stent thrombosis. A total of 850 patients with 1,039 lesions was randomized to the EES (n=425) and PES (n=425) groups. Ischemic-driven TVR at 2 yr was 3.8% in the PES and 1.2% in the EES group (P for non-inferiority=0.021). MACE rates were significantly different; 5.6% in PES and 2.5% in EES (P = 0.027). Rates of MI (0.8% in PES vs 0.2% in EES, P = 0.308), all deaths (1.5% in PES vs 1.2% in EES, P = 0.739) and stent thrombosis (0.3% in PES vs 0.7% in EES, P = 0.325) were similar. The clinical outcomes of EES are superior to PES, mainly due to a reduction in the rate of ischemia-driven TVR.
Antineoplastic Agents, Phytogenic/administration & dosage/therapeutic use ; Coronary Artery Disease/*drug therapy/mortality ; Coronary Restenosis/prevention & control ; *Drug-Eluting Stents ; Female ; Humans ; Immunosuppressive Agents/administration & dosage/therapeutic use ; Male ; Middle Aged ; Paclitaxel/administration & dosage/*therapeutic use ; Percutaneous Coronary Intervention/*methods ; Prospective Studies ; Sirolimus/administration & dosage/*analogs & derivatives/therapeutic use ; Thrombosis ; Treatment Outcome

PURPOSE: Thiazolidinediones are insulin-sensitizing agents that reduce neointimal proliferation and the adverse clinical outcomes associated with percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM). There is little data on whether or not low dose pioglitazone reduces adverse clinical outcomes. MATERIALS AND METHODS: The study population included 121 DM patients with coronary artery disease and they were randomly assigned to 60 patients taking 15 mg of pioglitazone daily in addition to their diabetic medications and 61 patients with placebo after the index procedure with drug-eluting stents (DESs). The primary end points were rate of in-stent restenosis (ISR) and change in atheroma volume and in-stent neointimal volume. The secondary end points were all-cause death, myocardial infarction (MI), stent thrombosis and re-PCI. RESULTS: There were no statistical differences in the clinical outcomes and the rate of ISR between the two groups [all-cause death; n=0 (0%) in the pioglitazone group vs. n=1 (1.6%) in the control group, p=0.504, MI; n=2 (3.3%) vs. n=1 (1.6%), p=0.465, re-PCI; n=6 (10.0%) vs. n=6 (9.8%), p=0.652, ISR; n=4 (9.3%) vs. n=4 (7.5%), p=1.000, respectively]. There were no differences in changes in neointimal volume, percent neointimal volume, total plaque volume and percent plaque volume between the two groups on intravascular ultrasonography (IVUS) study. CONCLUSION: Our study demonstrated that low dose pioglitazone does not reduce rate of ISR, neointimal volume nor atheroma volume in DM patients who have undergone PCI with DESs, despite the limitations of the study.
Aged ; Coronary Artery Disease/drug therapy/radiography/*therapy ; Coronary Restenosis/*prevention & control ; *Drug-Eluting Stents ; Female ; Humans ; Hypoglycemic Agents/therapeutic use ; Male ; Middle Aged ; Thiazolidinediones/administration & dosage/*therapeutic use

OBJECTIVETo evaluate the safety and efficiency of local paclitaxel delivery using the double-balloon perfusion catheter to prevent restenosis in the canine coronary artery.

METHODSTwenty domestic canines underwent bare-mental stent implantation after balloon injure of the left coronary artery. A novel double-balloon perfusion catheter was used to deliver the drug locally in the canine coronary artery. In the treatment group (n = 15), paclitaxel (10 ml, 20 micromol/L) was delivered using the double-balloon perfusion catheter before stent implantation. In the control group (n = 5), 10 ml saline was delivered using the double-balloon perfusion catheter before stent implantation. The perfusion time in both groups was (26.45 +/- 5.18) s. Animals underwent coronary angiography and optical coherence tomography (OCT) 90 days after stent implantation and were sacrificed. Vessels were perfusion-fixed and morphometric analysis was performed using conventional techniques.

RESULTSCoronary angiography results showed restenosis rate in control group was significantly higher than that in treatment group (60% vs. 33.33%, P < 0.05). The parameters of OCT showed in treatment group and control group: the neointimal thickness was (0.19 +/- 0.08) mm and (0.38 +/- 0.03) mm, the neointimal area was (1.52 +/- 0.49) mm2 and (2.51 +/- 0.47) mm2, the lumen area was (3.50 +/- 0.66) mm2 and (2.78 +/- 0.57) mm2, the extent of stenosis was (30.13 +/- 8.56)% and (47.40 +/- 4.50)%, and all the variances above were significantly different between the two groups (P < 0.05). The histologic parameters showed in treatment group and control group: the neointimal thickness was (0.22 +/- 0.10) mm and (0.47 +/- 0.05) mm, the neointimal area was (1.85 +/- 0.78) mm2 and (3.43 +/- 0.25) mm2, the lumen area was (3.15 +/- 0.43) mm2 and (1.85 +/- 0.55) mm2, the extent of stenosis was (36.00 +/- 10.97)% and (65.40 +/- 8.23)%, and all the variances above were also significantly different between the two groups (P < 0.05). The stents of both the groups were fully endothelialized. No thrombus or aneurysm was found in stents.

CONCLUSIONLocal delivery of paclitaxel with the double-balloon perfusion catheter to prevent restenosis in coronary stents is safe and efficient.

Angioplasty, Balloon, Coronary ; Animals ; Catheters ; Coronary Restenosis ; prevention & control ; Disease Models, Animal ; Dogs ; Injections ; Paclitaxel ; administration & dosage ; therapeutic use ; Stents

OBJECTIVETo evaluate the safety and efficacy of Xiongshao Capsule (XS), consisting of Chuangxiongol and paeoniflorin, in preventing restenosis after percutaneous coronary intervention (PCI) in senile coronary heart disease (CHD) patients.

METHODSA multi-center, randomized, double-blind, placebo-controlled trial was conducted. A total of 335 CHD patients were randomly assigned to treatment with oral administration of XS, or a placebo for 6 months after successful PCI. A clinical follow-up was performed at 1, 3 and 6 months after PCI and an angiographic follow-up was scheduled at 6 months. The primary endpoint was angiographic restenosis defined as a luminal stenosis ≥ 50% in follow-up. The secondary endpoints were combined incidence of death, target lesion nonfatal myocardial infarction, repeat target-vessel angioplasty, and coronary artery bypass graft surgery (CABG). The follow-up for the above clinical endpoint events was continued to 1 year after PCI.

RESULTSThe subgroup analysis of 152 senile patients (68 cases angiographic follow-up) showed that the restenosis rates tended to reduce in the XS group as compared with that in the placebo group (24.32% vs. 38.71%, P > 0.05), and the minimum lumen diameter (MLD) significantly increased in the follow-up (2.15 ± 0.84 for XS vs. 1.73 ± 0.91 for placebo, P < 0.05). The incidence of recurrent angina at 3 and 6 months after PCI was also significantly reduced in the XS group (4.11% and 12.33%) as compared with those in the placebo group (17.72% and 43.04%), but there was no significant difference in the combined incidence of clinical outcomes (6.85% in the XS group vs. 11.39% in the placebo group, P > 0.05). No significant adverse reactions occurred within the 6-month follow-up period in the XS group.

CONCLUSIONAdministration of XS in addition to standardized Western medication for 6 months is demonstrated to be safe and effective in reducing post-PCI recurrent angina and inhibiting luminal restenosis after PCI in senile CHD patients.

Aged ; Angina Pectoris ; complications ; diagnostic imaging ; epidemiology ; Angioplasty, Balloon, Coronary ; adverse effects ; Capsules ; China ; epidemiology ; Coronary Angiography ; Coronary Restenosis ; diagnostic imaging ; drug therapy ; etiology ; prevention & control ; Double-Blind Method ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Endpoint Determination ; Female ; Humans ; Male ; Placebos ; Recurrence