Background-In patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty, abciximab reduces major adverse cardiac events (MACE). Clinical trials have studied intravenous administration only. Intracoronary bolus application of abciximab causes very high local drug concentrations and may be more effective. We studied whether intracoronary bolus administration of abciximab is associated with a reduced MACE rate compared with the standard intravenous bolus application. Methods and Results-We stratified 403 consecutive patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty according to the type of application of abciximab. A 20-mg bolus of abciximab was given intravenously in 109 patients and intracoronarily in 294 patients. There were no differences between the groups with regard to diabetes mellitus, cardiogenic shock, successful intervention, or preprocedural and postprocedural TIMI flow. At 30 days, the incidence of MACE (death, myocardial infarction, urgent revascularization) was significantly lower in the patients with intracoronary compared with intravenous administration of abciximab (10.2% versus 20.2%; PϽ0.008), which was independent from stenting in multivariate analysis. The effect was most pronounced in patients with preprocedural TIMI 0/1 flow (MACE: intracoronary 11.8% versus intravenous 27.5%, PϽ0.002; nϭ273). Conclusions-In patients with acute myocardial infarction or unstable angina undergoing emergency coronary angioplasty, intracoronary bolus application of abciximab is associated with a reduction of MACE compared with the standard intravenous bolus application of abciximab. Prospective, randomized trials are warranted to further assess intracoronary application of abciximab.

No abstract

Background-Restenosis requiring reintervention limits the long-term success after coronary stent implantation.Thiazolidinediones, like pioglitazone or rosiglitazone, are oral antidiabetic drugs with additional antirestenotic properties. In a randomized, placebo-controlled, double-blind trial, we examined the effect of 6-month pioglitazone therapy on neointima volume after coronary stenting in nondiabetic coronary artery disease patients. Methods and Results-Fifty nondiabetic patients after coronary stent implantation were randomly assigned to pioglitazone (30 mg daily; pio) or placebo (control) treatment in addition to standard therapy, and neointima volume was assessed by intravascular ultrasound at the 6-month follow-up. Both groups were comparable with regard to baseline characteristics, angiographic lesion morphology, target vessel, and length of the stented segment. In addition, there were no statistical differences in minimal lumen diameter before and after intervention, as well as reference diameter after stent implantation. In this study population of nondiabetic patients, pio treatment did not significantly change fasting blood glucose, fasting insulin, or glycosylated hemoglobin levels, as well as lipid parameters. In contrast, pio treatment significantly reduced neointima volume within the stented segment, with 2.3Ϯ1.1 mm 3 /mm in the pio group versus 3.1Ϯ1.6 mm 3 /mm in controls (Pϭ0.04). Total plaque volume (adventitia-lumen area) was significantly lower at follow-up in the pio group (11.2Ϯ3.2 mm 3 /mm) compared with controls (13.2Ϯ4.2 mm 3 /mm; Pϭ0.04). Moreover, the binary restenosis rate was 3.4% in the pio group versus 32.3% in controls (PϽ0.01). Conclusions-Thus, 6-month treatment with pio significantly reduced neointima volume after coronary stent implantation in nondiabetic patients. These data bolster the hypothesis that antidiabetic thiazolidinediones, in addition to their metabolic effects, exhibit direct antirestenotic effects in the vasculature.

The present study examined the association of myocardial perfusion reserve index (MPRI) in cardiovascular magnetic resonance (CMR) with coronary microvascular dysfunction (CMD) and serum levels of markers of inflammation or endothelial activation. Twelve patients with typical angina pectoris without coronary artery disease were enrolled in this study, and CMR perfusion was analyzed using a steady-state-free-precession sequence with 3 short axis slices per heartbeat during first pass of 0.025 mmol Gadolinium-DTPA/kg body weight. The upslope of myocardial signal intensity curves was used to calculate MPRI. CMD was assessed by intracoronary Doppler flow measurement and biplane angiography. Both MPRI and CMD were assessed during endothelium-independent stimulation with intravenous adenosine and during endothelium-dependent stimulation with intracoronary infusion of acetylcholine. Serum values of soluble CD40 ligand (sCD40L), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), and C-reactive protein (CRP) were measured. Impaired MPRI correlated significantly with a decrease in coronary blood flow reserve after both endothelium-dependent (p = 0.033) and endothelium-independent (p = 0.022) stimulation. Serum levels above the median of all normal ranged biomarkers sCD40L, TNF-alpha, IL-6, sICAM-1 and CRP were associated with an impaired MPRI for stimulation with adenosine as well as acetylcholine. In multivariable analyses, sCD40L (p < 0.001) and TNF-alpha (p = 0.011) were significantly associated with a decrease in MPRI on adenosine, as were TNF-alpha (p = 0.016) and sICAM-1 (p = 0.022) for a decrease in MPRI on acetylcholine. MPRI on adenosine significantly correlated with MPRI on acetylcholine (p < 0.001). Therefore, the present study demonstrates safety and feasibility of an intracoronary infusion of acetylcholine during CMR perfusion analysis, thus allowing direct assessment of endothelial dependent vasomotor function at the myocardial level by CMR. Furthermore, we show that an impaired myocardial perfusion reserved in CMR is associated with established biomarkers of early atherosclerosis and significantly correlated with CMD. CMR combined with adenosine could be proposed as a non-invasive tool to evaluate CMD.

We conclude that the use of the slow-release Taxus-Express stent has the potential to be superior regarding angiographic and clinical outcome compared with its bare-metal counterpart for treatment of SVG lesions within a 12-month follow-up. A large, randomized trial including a long follow-up period is now required to prove the results of the meta-analysis.