Rationale of decreasing low-density lipoprotein cholesterol below 70 mg/dL in patients with coronary artery disease: A retrospective virtual histology-intravascular ultrasound study

Background: The associations between statin and coronary plaque compositional changes were re­ported according to the use of high dose or not. An evaluation of the impact of low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL by using real world dosages of statin on coronary plaque composition was undertaken. Methods: The study subjects consisted of 61 patients (mean 59.9 years old, 45 males) who underwent percutaneous coronary intervention, baseline and follow-up (F/U; mean 8.4 months) virtual histology- -intravascular ultrasound (VH-IVUS) examination. Change of plaque composition at peri-stent area, which was selected in order to measure the identical site at F/U study, was compared according to the F/U LDL-C level. Results: Body mass index, prevalence of dyslipidemia, baseline total cholesterol and baseline LDL-C were significantly lower in F/U LDL-C < 70 mg/dL group (14 segments in 10 patients) than F/U LDL-C ≥ 70 mg/dL group (79 segments in 51 patients). F/U high-density lipoprotein cholesterol (HDL-C, OR 1.06, 95% CI 1.00–1.11, p = 0.054) and F/U LDL-C < 70 mg/dL (OR 3.43, 95% CI 0.97–12.17, p = 0.056) showed strong tendency of regression of necrotic core volume (NCV) ≥ 10%. In multivariable logis­tic regression analysis, F/U HDL-C (OR 1.07, 95% CI 1.01–1.14, p = 0.020) and F/U LDL-C < 70 mg/dL (OR 8.02, 95% CI 1.58–40.68, p = 0.012) were the independent factors for regression of NCV ≥ 10%. Conclusions: Follow-up LDL-C level < 70 mg/dL with any types of statins and increase of HDL-C were associated with regression of NCV ≥ 10% in patients with coronary artery disease

In-stent restenosis-prone coronary plaque composition: A retrospective virtual histology-intravascular ultrasound study

  Background: The mechanism of in-stent restenosis (ISR) is multifactorial, which includes biological, mechanical and technical factors. This study hypothesized that increased inflammatory reaction, which is known to be an important atherosclerotic process, at a culprit lesion may lead to higher restenosis rates. Methods: The study population consisted of 241 patients who had undergone percutaneous coronary intervention with virtual histology-intravascular ultrasound (VH-IVUS) and a 9-month follow-up coronary angiography. Compared herein is the coronary plaque composition between patients with ISR and those without ISR. Results: Patients with ISR (n = 27) were likely to be older (66.2 ± 9.5 years vs. 58.7 ± 11.7 years, p = 0.002) and have higher levels of high-sensitivity C-reactive protein (hs-CRP, 1.60 ± 3.59 mg/dL vs. 0.31 ± 0.76 mg/dL, p < 0.001) than those without ISR (n = 214). VH-IVUS examination showed that percent necrotic core volume (14.3 ± 8.7% vs. 19.5 ± 9.1%, p = 0.005) was higher in those without ISR than those with ISR. Multivariate analysis revealed that hs-CRP (odds ratio [OR] 3.334, 95% con­fidence interval [CI] 1.158–9.596, p = 0.026) and age (OR 3.557, 95% CI 1.242–10.192, p = 0.018) were associated with ISR. Conclusions: This study suggests that ISR is not associated with baseline coronary plaque composition but is associated with old age and increased expression of the inflammatory marker of hs-CRP. (Cardiol J 2018; 25, 1: 7–13

Study design and rationale of 'Influence of Cilostazol-based triple anti-platelet therapy on ischemic complication after drug-eluting stent implantation (CILON-T)' study: A multicenter randomized trial evaluating the efficacy of Cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease

<p>Abstract</p> <p>Background</p> <p>Current guidelines recommend dual anti-platelet therapy, aspirin and clopidogrel, for patients treated with drug-eluting stent for coronary heart disease. In a few small trials, addition of cilostazol on dual anti-platelet therapy (triple anti-platelet therapy) showed better late luminal loss. In the real-world unselected patients with coronary heart disease, however, the effect of cilostazol on platelet reactivity and ischemic vascular events after drug-eluting stent implantation has not been tested. It is also controversial whether there is a significant interaction between lipophilic statin and clopidogrel.</p> <p>Methods/Design</p> <p>CILON-T trial was a prospective, randomized, open-label, multi-center, near-all-comer trial to demonstrate the superiority of triple anti-platelet therapy to dual anti-platelet therapy in reducing 6 months' major adverse cardiovascular/cerebrovascular events, composite of cardiac death, nonfatal myocardial infarction, target lesion revascularization and ischemic stroke. It also tested whether triple anti-platelet therapy is superior to dual anti-platelet therapy in inhibiting platelet reactivity in patients receiving percutaneous coronary intervention with drug-eluting stent. Total 960 patients were randomized to receive either dual anti-platelet therapy or triple anti-platelet therapy for 6 months and also, randomly stratified to either lipophilic statin (atorvastatin) or non-lipophilic statin (rosuvastatin) indefinitely. Secondary endpoints included all components of major adverse cardiovascular/cerebrovascular events, platelet reactivity as assessed by VerifyNow P2Y12 assay, effect of statin on major adverse cardiovascular/cerebrovascular events, bleeding complications, and albumin-to-creatinine ratio to test the nephroprotective effect of cilostazol. Major adverse cardiovascular/cerebrovascular events will also be checked at 1, 2, and 3 years to test the 'legacy' effect of triple anti-platelet therapy that was prescribed for only 6 months after percutaneous coronary intervention.</p> <p>Discussion</p> <p>CILON-T trial will give powerful insight into whether triple anti-platelet therapy is superior to dual anti-platelet therapy in reducing ischemic events and platelet reactivity in the real-world unselected patients treated with drug-eluting stent for coronary heart disease. Also, it will verify the laboratory and clinical significance of drug interaction between lipophilic statin and clopidogrel.</p> <p>Trial Registration</p> <p>National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT00776828).</p

Design and rationale of a randomized control trial testing the effectiveness of combined therapy with STAtin plus FENOfibrate and statin alone in non-diabetic, combined dyslipidemia patients with non-intervened intermediate coronary artery disease - STAFENO study

Background Despite the chronicled success of low-density lipoprotein cholesterol (LDLc)-lowering statin therapy, substantial residual cardiovascular (CV) disease risk remains a problem worldwide, highlighting the need to for combination therapies targeting non-LDLc factors, such as with fenofibrate. Methods/design The STAFENO trial is a prospective, randomized, open-label, multi-center trial to compare the effect of statin plus fenofibrate with statin alone on the reduction and stabilization of plaque in non-diabetic, combined dyslipidemia patients with non-intervened, intermediate coronary artery disease (CAD) using virtual histology-intravascular ultrasound at 12 months. A total of 106 eligible patients are planned to be randomized to receive either a combination therapy (rosuvastatin 10 mg plus fenofibrate 160 mg/day) or monotherapy (rosuvastatin 10 mg/day) for 12 months. The primary endpoint of this study is the percentage change in the necrotic core volume. Secondary endpoints include changes in tissue characteristics and 1-year major CV events, including all-cause mortality, CV mortality, nonfatal myocardial infarction, stroke, and revascularization of the intervened and non-intervened lesions. Discussion The STAFENO trial will address whether combination treatment of statin and fenofibrate has an additive beneficial effect compared to statin alone on the reduction and stabilization of plaque and CV events in non-diabetic, combined dyslipidemia patients with non-intervened intermediate CAD. Trial registration ClinicalTrials.gov, NCT02232360. Registered 9 February 2014. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0004ULE&selectaction=Edit&uid=U00023SZ&ts=2&cx=juppd2This is an investigator-initiated clinical trial with grant support from Daewoong Pharmaceutical Co. Ltd (Seoul, Korea). The sponsor has no role in the development of study protocols or study processes, including site selection, management, and data collection and analysis. The authors are solely responsible for the design and editing of this paper and its final content

Metronidazole-induced encephalopathy in a patient with liver cirrhosis

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis

Serum Levels of Advanced Glycation End Products Are Associated with In-Stent Restenosis in Diabetic Patients

The formation of advanced glycation end products (AGEs), in various tissues has been known to enhance immunoinflammatory reactions and local oxidant stresses in long standing diabetes. Recently, AGEs have been reported to play a role in neointimal formation in animal models of arterial injury. We attempted to determine whether the serum levels of AGEs are associated with coronary restenosis in diabetic patients. Blood samples were collected from diabetic patients with coronary artery disease undergoing stent implantation and the serum levels of AGEs were analyzed by the fluorescent intensity method. The development of in-stent restenosis (ISR) was evaluated by a 6-month follow-up coronary angiography. A total of 263 target lesions were evaluated, in 203 patients. The ISR rate in the high-AGE (>170 U/ml) group (40.1%) was significantly higher than in the low-AGE group (≤170 U/ml) (19.6%) (p<0.001). Furthermore, multivariate analysis revealed that a high level of serum AGEs is an independent risk factor for the development of ISR (odds ratio, 2.659; 95% CI, 1.431-4.940; p=0.002). The serum levels of AGEs constitute an excellent predictive factor for ISR, and should be one of the guidelines for medical therapy and interventional strategy to prevent ISR in diabetic patients