Thibaud Meurice

Restenosis rates in diabetic patients: a comparison of coronary stenting and balloon angioplasty in native coronary vessels.

BACKGROUND Diabetes is a major risk factor for restenosis after coronary balloon angioplasty. Recent studies have shown that coronary stenting significantly reduces restenosis compared with balloon angioplasty alone. However, limited information is available on the effect of coronary stenting in diabetic patients. METHODS AND RESULTS We designed this study to analyze the effect of diabetes on restenosis in patients treated with either balloon angioplasty or coronary stenting who were enrolled in a 6-month angiographic follow-up program. Three hundred consecutive patients, 19% of whom were diabetics, who underwent coronary stent implantation during a single-vessel procedure on native coronary vessels and who had 6-month angiographic follow-up constituted the study group (stent group). Three hundred consecutive patients who underwent 6-month angiographic follow-up after single-vessel conventional balloon angioplasty served as control patients (balloon group). Preprocedural, postprocedural, and follow-up angiograms were analyzed with quantitative angiography. In the balloon group, the restenosis rate was almost twofold higher in diabetic than in nondiabetic patients (63% versus 36%; P=.0002) owing to both a greater late loss (0.79+/-0.70 versus 0.41+/-0.61 mm, respectively; P<.0001) and a higher rate of late vessel occlusion (14% versus 3%, respectively; P<.001). In the stent group, restenosis rates were similar in diabetics and nondiabetics (25% versus 27%, respectively). Furthermore, in the stent group, late loss (0.77+/-0.65 versus 0.79+/-0.57 mm, respectively) and the rate of late vessel occlusion (2% versus 1%, respectively) did not differ significantly between diabetic and nondiabetic patients. CONCLUSIONS Although diabetics have increased rates of restenosis and late vessel occlusion after simple balloon angioplasty, they have the same improved outcome with coronary stenting that has been documented in nondiabetic patients.

Effects of coronary stenting on vessel patency and long-term clinical outcome after percutaneous coronary revascularization in diabetic patients.

OBJECTIVES We sought to compare coronary stent implantation with balloon angioplasty (BA), in a diabetic population, in terms of the six-month angiographic outcome and four-year clinical events. BACKGROUND Diabetic patients have a poor angiographic and clinical outcome after standard coronary BA. To date, it is still unclear whether stent implantation may improve this outcome. METHODS We investigated this issue by individual matching of 314 diabetic patients treated with either coronary stenting or standard BA. These two groups were derived from a population of consecutive diabetic patients (1993 to 1996). Matching criteria were gender, anti-diabetic regimen, stenosis location, reference diameter, and minimal luminal diameter (+/-0.4 mm). One lesion per patient was considered for matching. RESULTS Baseline characteristics were similar between the two groups of 157 patients. At six months, the rates of restenosis (27% vs. 62%; p < 0.0001) and occlusion (4% vs. 13%; p < 0.005) were lower in the stent group than in the BA group. This was associated with a significant decrease in ejection fraction at six months in the BA group (p = 0.02) while, during the same period, no change was observed in the stent group (p = NS). Subgroup analysis demonstrated that angiographic benefit was consistent among the subgroups. At four years, the combined clinical end point of cardiac death and non-fatal myocardial infarction was lower in the stent group (14.8% vs. 26.0%; p = 0.02), as was the need for repeat revascularization (35.4% vs. 52.1%; p = 0.001). CONCLUSIONS In a population of diabetic patients, coronary stent implantation was associated with a highly beneficial effect on the six-month angiographic outcome and four-year clinical events compared with standard BA.

Effect of ACE inhibitors on angiographic restenosis after coronary stenting (PARIS): a randomised, double-blind, placebo-controlled trial

BACKGROUND The DD genotype for the angiotensin-I converting enzyme (ACE I) deletion allele (D) polymorphism is a possible genetic risk factor for restenosis after coronary stent implantation. We aimed to establish whether or not blockade of ACE with high doses of ACE inhibitors could reduce this risk of angiographic restenosis. METHODS We characterised the ACE I/D polymorphism in 345 consecutive patients who were undergoing coronary stenting. 115 had the DD genotype. We assigned 91 of these 115 patients to quinapril 40 mg daily (n=46) or placebo (n=45). Treatment was started within 48 h after stent implantation and continued for 6 months. 79 patients complied with the protocol and underwent follow-up angiography after 6 months. FINDINGS Our primary endpoint of late loss in minimum lumen diameter (a quantitative index of restenosis) was significantly higher in the quinapril group than in the controls (mean 1.11 mm [SD 0.70] vs 0.76 mm [0.60]; p=0.018). Secondary endpoints also showed consistent trends towards increased angiographic restenosis in the treatment group. INTERPRETATION Contrary to our expectations, ACE inhibitor treatment did not reduce restenosis after coronary stent implantation in patients with DD genotype, but was associated with an exaggerated restenotic process when compared with administration of placebo.

Mechanisms and prevention of restenosis: from experimental models to clinical practice

Percutaneous transluminal coronary angioplasty (PTCA) was first introduced by Andreas Gruentzig in 1977 [l] as an alternative form of myocardial revascularization for patients with coronary artery disease. During the early years of its application, PTCA was limited to patients with single proximal coronary artery disease, well preserved left ventricular function, and stable angina refractory to medical treatment. Almost twenty years later, PTCA has become a well established technique for myocardial revascularization of patients with unstable angina [2], patients with an evolving myocardial infarction [3], patients with multivessel disease [4], and patients with depressed left ventricular function [5]. However, PTCA remains limited by restenosis that occurs in 30-60% of cases despite a successful procedure [6-g]. Assuming 500000 PTCA procedures per year in the United States [lo], more than 150000 patients develop restenosis every year. Although some restenoses may be silent, most of these patients present with recurrent angina and a significant proportion will need a new revascularization procedure. Decreasing the rate of restenosis would sharply lower the long-term cost of PTCA; in the United States, a reduction of the rate of restenosis from an hypothetical 33% to 25% might save as much as

Prognosis of patients with stable coronary artery disease (from the CORONOR study).

750 million annually [IO]. Numerous agents have been used to prevent restenosis, and the results of more than 40 multicenter randomized clinical trials have now been published [11,12]. Despite intensive investigation in this area, no pharmacological therapy has yet been found to be useful in preventing restenosis. The purpose of this report is twofold: first, to review the available information relevant to the mechanisms of restenosis, and, second, to review the strategies currently being explored as possible approaches to the control of coronary restenosis after PTCA.

Effects of Coronary Stenting on Restenosis and Occlusion After Angioplasty of the Culprit Vessel in Patients With Recent Myocardial Infarction

There are limited data on the prognosis of patients with stable coronary artery disease (CAD) in modern clinical practice. We conducted a multicenter study enrolling 4,184 outpatients with stable CAD defined as previous myocardial infarction (>1 year ago), previous coronary revascularization (>1 year ago), and/or ≥50% coronary stenosis by angiography. Clinical follow-up was performed after 2 years. All cases of death were adjudicated and the mortality rate was compared with expected mortality of persons of the same age and gender in the same geographical area. Mean age was 66.9±11.6 years; 77.7% were men. There was a wide prescription of secondary prevention drugs: antithrombotic drugs, 99.3%; β blockers, 79.4%; statins, 92.2%; and antagonists of the angiotensin system, 81.9%. Two-year follow-up was obtained for 99.2% of the patients. There were 271 deaths (3.3/100 patient-years). The mortality rate was similar to the expected mortality in the general population (p=0.93). Most deaths were noncardiovascular (1.8/100 patient-years). Among cardiovascular deaths, the leading causes were heart failure death (0.4/100 patient-years) and sudden death (0.4/100 patient-years); in contrast, there were few deaths related to vascular causes (stroke, 0.2/100 patient-years and myocardial infarction, 0.1/100 patient-years). Age, diabetes, multivessel CAD, the absence of previous coronary revascularization, previous hospitalization for decompensated heart failure, a low ejection fraction, a low estimated glomerular filtration rate, and the absence of statin treatment were independent predictors of mortality. In conclusion, the mortality rate of patients with stable CAD in modern clinical practice is similar to that of the general population and is mostly due to noncardiovascular causes.

Basic Fibroblast Growth Factor Restores Endothelium-Dependent Responses After Balloon Injury of Rabbit Arteries

BACKGROUND PTCA of an infarct-related lesion is associated with a high rate of restenosis and/or vessel occlusion. Recent studies have shown that coronary stenting in patients with stable or unstable angina is associated with a significant reduction in the restenosis rate compared with conventional balloon angioplasty. However, no information is available concerning the long-term effect of coronary stenting at infarct-related lesions compared with balloon angioplasty alone. METHODS AND RESULTS One hundred consecutive patients undergoing stent implantation at an infarct-related lesion and systematic 6-month angiographic follow-up were matched for major pre-PTCA clinical and angiographic variables with a group of patients undergoing conventional angioplasty. Preprocedural, postprocedural, and 6-month follow-up angiograms were analyzed with quantitative angiography. Coronary stenting was performed as a bailout procedure after failed balloon angioplasty in 20%, for a suboptimal result after balloon angioplasty in 71%, and electively in 9%. Stent implantation was associated with a higher acute gain than balloon angioplasty. At follow-up, the minimal lumen diameter was significantly (P<.0001) larger in the stent group (1.72+/-0.69 versus 1.23+/-0.72 mm). Restenosis (>50% DS at follow-up) occurred in 27% of the stent group versus 52% of the balloon group (P<.005). At follow-up, total occlusion at the dilated site occurred in 1% of the stent group versus 14% of the balloon group (P<.005). CONCLUSIONS Coronary stenting of infarct-related lesions is associated with a highly beneficial effect on 6-month angiographic outcome compared with balloon angioplasty alone. Further studies are needed to establish whether the beneficial effect of coronary stenting on long-term vessel patency is associated with an improvement in left ventricular function or in clinical outcome.

Basic fibroblast growth factor increases tissue factor expression in circulating monocytes and in vascular wall

BACKGROUND After experimental angioplasty, partial or complete reendothelialization of the denuded surface occurs; the function of the regenerated endothelium has, however, been shown to be abnormal. Basic fibroblast growth factor (bFGF) is mitogenic for endothelial cells in vitro and in vivo. We investigated whether chronic administration of bFGF in a rabbit model of balloon denudation might not only improve endothelial regrowth but also restore normal physiological responses to endothelium-dependent agonists. METHODS AND RESULTS Thirty-nine New Zealand White rabbits underwent balloon denudation of the right iliac artery. Twenty rabbits received intravenous administration of bFGF (2.5 micrograms twice a week for 2 weeks). Nineteen rabbits receiving saline injections served as controls. Animals were killed on day 28 for assessment of reendothelialization and neointimal thickening and for analysis of in vitro vasoreactivity. Animals in the bFGF group had a significantly (P<.005) greater degree of reendothelialization than controls (115 +/- 13 versus 55 +/- 6 mm2). Neointimal thickening was similar in the two groups. Four weeks after denudation, endothelium-independent responses did not differ significantly between the two groups. In contrast, the maximal endothelium-dependent acetylcholine-induced relaxation of the bFGF-treated animals (Emax, 40 +/- 7%) was significantly greater than that of the control group (Emax, 11 +/- 9%; P<.05). CONCLUSIONS Systemic administration of bFGF restores, in large part, the responses of previously denuded arterial segments to endothelium-dependent vasodilators. Angiogenic growth factors may help to reestablish normal endothelial cell function in patients who have undergone angioplasty.

Prognostic impact of ß-blocker use in patients with stable coronary artery disease

BACKGROUND Basic fibroblast growth factor (bFGF) promotes vascular repair and angiogenesis and can induce in vitro tissue factor (TF), a potent agent initiating thrombogenesis, which probably plays a role in angiogenesis. We investigated whether bFGF administration induced TF expression by monocytes and vascular cells. METHODS AND RESULTS We studied TF expression in normally fed (n=16) and cholesterol-fed (2% for 6 weeks, n=16) rabbits. Animals were then randomized to receive intravenous bFGF (2.5 microg twice weekly for 3 weeks) or saline injections. TF expression was evaluated in mononuclear cells from arterial blood and in aortic sections by an immunohistochemical assay using a monoclonal anti-rabbit TF antibody (activator protein 1). Monocyte TF expression was increased by bFGF administration in both normal and hypercholesterolemic rabbits (129+/-45 versus 19+/-3 mU TF/1000 monocytes, P<0.05, and 31+/-12 versus 7+/-1 mU TF/1000 monocytes, P<0.005, respectively) and was further increased by stimulation of monocytes by endotoxin in vitro. TF expression was lower in hypercholesterolemic rabbits than in normal rabbits. In the media of the vascular wall, bFGF induced strong TF expression in normal rabbits and only weak TF expression in hypercholesterolemic ones. CONCLUSIONS This study demonstrates that systemic administration of bFGF induces an impressive increase of TF expression in circulating monocytes and in the vascular wall in normal and to a lower extent in hypercholesterolemic rabbits. The significance of this observation in terms of inducing thrombosis in vivo needs clarification.

Prevention of Restenosis: Future Directions

Objective To assess the association of ß-blocker use with cardiovascular mortality in patients with stable coronary artery disease (CAD). Methods We analysed the data of 4184 outpatients included in a prospective cohort study on stable CAD. Two groups were formed based on ß-blocker use at enrolment. Two propensity score analyses were performed to control for differences in covariates: one with adjustment among the entire cohort, and the other with propensity score matching. The outcome variable was cardiovascular mortality after a 2-year follow-up. Results There were 3320 patients with ß-blocker use. Younger age, hypertension, diabetes, prior myocardial infarction, multivessel CAD, prior coronary revascularisation, prior stroke, prior hospitalisation for heart failure and a low LVEF were associated with ß-blocker use. Clinical follow-up data were obtained for 4149 patients (99.2%). When adjusted on propensity score, ß-blocker use was associated with a HR for cardiovascular mortality of 0.64 (0.42–0.98) in the whole cohort (p=0.04). After one-to-one propensity score matching, both groups (n=839 in each group) were well matched on covariates. The cardiovascular mortality rate in the propensity-matched cohort was significantly lower in patients with ß-blocker use with a HR of 0.43 (0.22–0.82) (p=0.011). Non-cardiovascular mortality was similar in both groups. These results were consistent across different subgroups. Conclusions In this observational study of patients with stable CAD, the use of ß-blockers was associated with a lower risk of cardiovascular mortality.