Publications

No abstract is provided for this article.

Background: In the main publication for LIPS (Lescol Intervention Prevention Study), a 22% relative risk (RR) reduction for major adverse cardiac events (MACE) was found among those who used fluvastatin after a successful first percutaneous coronary intervention (PCI). However, intent-to-treat (ITT) analysis of clinical studies generally provides an observed treatment effect that is likely to underestimate what the treatment effect would be if compliance were perfect, because compliance in a clinical trial is invariably <100% during long-term follow-up. Objective: The aim of this study was to analyze the relationship between compliance and treatment effect in LIPS. Methods: In LIPS, patients who had undergone a successful first PCI were randomized to receive fluvastatin 40 mg BID or placebo BID for 3 to 5 years. The primary end point was survival time free of MACE (ie, cardiac death, nonfatal myocardial infarction, or reintervention procedure), and a Cox proportional hazards regression model with time-dependent covariates was used to predict the effect that fluvastatin would have had if trial medication had been continued. Logistic regression was used to determine factors influencing discontinuation of trial medication. Results: A total of 1677 patients were enrolled in LIPS: 844 in the fluvastatin group and 833 in the placebo group. In the fluvastatin group, 294 patients (34.8%) discontinued taking trial medication and 73 (8.6%) switched to another lipid-lowering medication, compared with 353 (42.4%) and 187 (22.4%) patients in the placebo group, respectively. The risk factor-adjusted RR of MACE with fluvastatin treatment was 0.74 (P = 0.004; 95% CI, 0.61–0.91). When also adjusted for noncompliance, the RR for fluvastatin versus placebo was 0.68 (P = 0.002; 95% CI, 0.53–0.86). Discontinuing fluvastatin without switching to another lipid-lowering medication increased the risk of MACE compared with that of patients who stayed on fluvastatin (RR = 2.27; P < 0.001; 95% CI, 1.60–3.23) and the increase in the risk of MACE was greater than that associated with discontinuing placebo (P = 0.032). Conclusions: The present study found a 32% RR reduction for experiencing MACE during fluvastatin treatment after a successful PCI in LIPS, when analysis allowed for noncompliance. This suggests that the ITT analysis discussed in the main LIPS publication underestimated the benefit of fluvastatin treatment. Our survival model also provided tentative evidence that discontinuing lipid-lowering medication might lead to a potentially harmful rebound effect in this patient group.

Background: While the utilization of integrated backscatter intravascular ultrasound (IB-IVUS) for the quantitative in vivo assessment of coronary plaque continues to grow, the validity of IB-IVUS images obtained from newly developed and conventional systems remains uncertain. Methods and Results: To assess the accuracy and reliability of a newly developed IB-IVUS system (VISIWAVE) as compared to the conventional system (Clearview), we compared quantitative IB-IVUS plaque characteristics in the 2 systems using 125 post-mortem specimens from 26 coronary arteries in 11 cadavers, as well as using 200 clinical plaques in 32 patients undergoing coronary intervention. The overall agreement between the histological and IB-IVUS diagnoses using VISIWAVE (Cohen's κ=0.82, 95%CI: 0.73-0.90) was similar to that using Clearview (Cohen's κ=0.80, 95%CI: 0.71-0.89). The 2 systems also demonstrated comparably high sensitivity and specificity. In the direct comparison, the overall agreement between IB-IVUS diagnoses using VISIWAVE and Clearview was also excellent (Cohen's κ=0.87, 95%CI: 0.78-0.95). In the clinical comparison, measured plaque dimensions were similar (VISIWAVE: 8.27±3.46mm2 vs. Clearview; 8.31±3.46mm2, P=0.44) and there was strong concordance between both greyscale and IB-IVUS parameters. Conclusions: There was close agreement of analyzed results in both systems when compared with the gold standard of histology. Both systems are able to reliably and accurately characterize coronary plaque and thereby make a valuable contribution to our understanding of atherosclerosis. (Circ J 2012; 76: 1678–1686)

No abstract is provided for this article.

Neutrophils are considered to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and severe asthma. Recent guidelines recommend the use of a combination of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA) in the treatment of COPD with exacerbations and asthma not adequately controlled by ICS alone. LABA have been proposed to have a synergistic effect with corticosteroids by activating glucocorticoid receptors. The aim of this study was to investigate the effect of β2-agonists on the inhibitory effects of corticosteroids on human neutrophil apoptosis. In addition, the effects of β2-agonists on spontaneous neutrophil apoptosis and on GM-CSF- and LTB4-afforded survival were also evaluated. Neutrophils were isolated from human blood under sterile conditions and cultured for 16 hours. Apoptosis was assessed by relative DNA fragmentation assay. Morphological analysis was used as a control method to confirm the occurrence of apoptosis. Salbutamol, formoterol and salmeterol prolonged the lifespan of budesonide- and fluticasone propionate-treated neutrophils by inhibiting apoptosis. Formoterol and salbutamol partly reversed the inhibitory effect of GM-CSF on neutrophil apoptosis. In contrast, the effects of β2-agonists on spontaneous neutrophil apoptosis and on LTB4-afforded survival were negligible. β2-agonists potentiate corticosteroid-induced neutrophil survival at clinically relevant drug concentrations. Whether these effects translate into clinically relevant changes in lung neutrophil numbers remains to be demonstrated.

Introduction: Acute ischemic stroke (AIS) is a common and lethal cerebral vascular disease. Early thrombus removal is crucial to the patient treatment and recovery. Clinical studies suggested that Direct Aspiration Thrombectomy (DAT) is a promising minimally invasive treatment option for AIS patients. It is necessary to summarize the hemodynamic studies about the DAT for further improvement of the technology. Methods: This paper reviewed the current in vitro and computer modelling studies of the hemodynamic response in the DAT, commenting on the merits and the deficiencies in the related research works reported in the literature. Results: Review of literature reveals that majority of current studies were focused on the comparison of the responses produced by using various suction systems on catheters of different calibers. For future technical improvement to facilitate clinical treatment, we suggest that further research to concentrate on more in-depth hemodynamic analysis of the DAT procedure, including replacement of the constant suction pressure with pulsatile suction pressure, comparison of contact aspiration and non-contact aspiration, and optimization of catheter tip design. Conclusions: This review summarized the concurrent technical development about the hemodynamic studies of the DAT technique and suggested directions for future improvement, which is helpful for the improvement of the AIS treatment planning and design optimization of next generation of interventional catheters.

AimsWe evaluated the feasibility and the acute performance of the everolimus-eluting bioresorbable vascular scaffolds (BVS) for the treatment of patients presenting with ST-segment elevation myocardial infarction (STEMI).

No abstract is provided for this article.