Early Statin Research Articles

Impact of prior chronic statin therapy and high-intensity statin therapy at discharge on circulating endothelial progenitor cell levels in patients with acute myocardial infarction: a prospective observational study.

Endothelial progenitor stem cells (EPCs) are mobilized to the peripheral circulation in response to myocardial ischemia, playing a crucial role in vascular repair. Statins have been shown to stimulate EPCs. However, neither the impact of previous statin therapy on EPC response of acute myocardial infarction (AMI) patients nor the effect of post-AMI high-intensity statin therapy on the evolution of circulating EPC levels has yet been addressed. Therefore, we aimed to compare circulating EPC levels between patients receiving long-term statin therapy before the AMI and statin-naive patients and to assess the impact of high-intensity statin therapy at discharge on the evolution of circulating EPCs post-AMI. This is a prospective observational study of 100 AMI patients. Circulating EPCs (CD45dimCD34 + KDR + cells) and their subpopulation coexpressing the homing marker CXCR4 were quantified by the high-performance flow cytometer FACSCanto II in whole blood, in two different moments: within the first 24h of admission and 3months post-AMI. Patients were followed up clinically for 2years. Patients previously treated with statins had significantly higher levels of EPCs coexpressing CXCR4 (1.9 ± 1.4 vs. 1.3 ± 1.0 cells/1,000,000 events, p = 0.031) than statin-naive patients. In addition, the subanalysis of diabetics (N = 38) also revealed that patients previously on statins had significantly greater numbers of both CD45dimCD34 + KDR + CXCR4+ cells (p = 0.024) and CD45dimCD34 + KDR + CD133+ cells (p = 0.022) than statin-naive patients. Regarding the evolution of EPC levels after the AMI, patients not on a high-intensity statin therapy at discharge had a significant reduction of CD45dimCD34 + KDR + and CD45dimCD34 + KDR + CXCR4+ cells from baseline to 3months follow-up (p = 0.031 and p = 0.005, respectively). However, patients discharged on a high-intensity statin therapy maintained circulating levels of all EPC populations, presenting at 3months of follow-up significantly higher EPC levels than patients not on an intensive statin therapy. Moreover, the high-intensity statin treatment group had significantly better clinical outcomes during the 2-year follow-up period than patients not discharged on a high-intensity statin therapy. Chronic statin therapy prior to an AMI strongly enhances the response of EPCs to myocardial ischemia, even in diabetic patients. Furthermore, high-intensity statin therapy after an AMI prevents the expected decrease of circulating EPC levels during follow-up. These results reinforce the importance of an early and intensive statin therapy in AMI patients.

Protective effects of some statins on epileptogenesis and depressive-like behavior in WAG/Rij rats, a genetic animal model of absence epilepsy.

Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) exert cholesterol-independent pleiotropic effects that include antithrombotic, antiinflammatory, and antioxidative properties. Moreover, both in vitro and in vivo studies have shown neuroprotective, antiseizure, and antiexcitotoxic effects of statins, suggesting their potential role in the treatment of neurologic diseases. Only a few studies have investigated whether statins modulate absence seizure activity and epileptogenesis. We investigated the effects of atorvastatin (5 and 10 mg/kg/day), simvastatin (10 mg/kg/day), and pravastatin (10 and 30 mg/kg/day), given orally for 17 consecutive weeks (starting at 45 days of age), on the development of absence seizures (electroencephalography [EEG] recordings), depressive-like behavior (forced swimming test [FST]), and anxiety levels (open field test [OF]) in Wistar Albino Glaxo/Rijswijk rats (WAG/Rij) rats at the age of 6 months (1 month after suspension). WAG/Rij rats are a genetic animal model of absence epilepsy, epileptogenesis, and mild-depression comorbidity. The effects of statins were also studied after acute intraperitoneal injection for 4 h after administration of various doses in 6-months-old rats. Plasma cholesterol levels were measured throughout drug treatment. We found that early long-term statin treatment possesses antiepileptogenic properties, reduced immobility time in the FST, and reduced anxiety in the OF, whereas they were not effective against established absence seizures when acutely administered. The observed effects were not related to changes in plasma cholesterol levels, which remained unchanged during drug treatment. Our results suggest that statins administration might be a possible intervention and promising strategy for preventing the epileptogenesis and/or behavioral comorbidity.

Impact of statin usage patterns on outcomes after percutaneous coronary intervention in acute myocardial infarction: Korea Working Group on Myocardial Infarction registry (KorMI) study.

BackgroundThe benefit of statin use after acute ST-segment elevation myocardial infarction (STEMI) has been well established, however, the influence of the timing of statin administration has not been elucidated. The objective of this study focused on early clinical outcomes after percutaneous coronary intervention (PCI).MethodsThis analysis of the Korea Working Group on Myocardial Infarction registry (KorMI) study included 3,584 STEMI patients (mean age, 63 ± 13 years; male, 2,684, 74.9%) undergoing PCI from January 2008 to June 2009. Rates of major adverse cardiac events (MACE: all-cause death, recurrent MI, and target lesion revascularization) were compared among patients grouped according to statin therapy timing: I, both during and after hospitalization (n = 2,653, 74%); II, only during hospitalization (n = 309, 8.6%); III, only after discharge (n = 157, 4.4%); and IV, no statin therapy (n = 465, 13%). Mean follow-up duration was 234 ± 113 days.ResultsMultivariate factors of statin use during hospitalization included prior statin use, multiple diseased vessels, final thrombolysis in myocardial infarction flow grade III, and low-density lipoprotein cholesterol level. At 6-month follow-up, groups III and IV had the highest MACE rates (2.3%, 3.9%, 5.1%, and 4.9% for groups I-IV, respectively, P = 0.004). After adjusting for confounders, groups II-IV had a higher MACE risk than group I [hazard ratio (HR): 3.20, 95% confidence interval (95%CI): 1.31–7.86, P = 0.011; HR: 3.84, 95%CI: 1.47–10.02, P = 0.006; and HR: 3.17, 95%CI: 1.59–6.40, P = 0.001; respectively].ConclusionsThis study, based on the national registry database, shows early and continuous statin therapy improvs early outcomes of STEMI patients after PCI in real-world clinical practice.

Applicated value of rosuvastatin in the treatment of coronary heart disease patients with diabetes

Objective To compare main adverse cardiac events of patients with coronary heart disease and diametes,but normal lipids after statin on lowering lipids , and to bring out necessity of early lowering lipids . Methods A total of 324 patients with coronary heart disease and diametes were enrolled ,LDL-C was measured in-hospital for all patients and LDL-C〈3.36mmol/L suitable for the experiment .They were divided into statin group （n=176,rosuvastatin 10 mg/d）and control group（n=148）randomly,all patients received second prevention for cor-onary heart disease including anti-platelet,anti-myocardial ischemia,smoke quitting,adjust diets and exercise,the CAG or PTCA（and stent implanting）,CABG.the end events were main adverse cardiac events （cardiac events,recur-rent angina and target vessel reconstruction ）.The mean follow-up time was（13 ±6）months.Results The fasting plasma glucose,LDL-C,hs-CRP in statin group were all significantly lower than those of control group [FPG：（5.3 ± 0.9）vs.（6.7 ±1.2）mmol/L,P=0.042;LDL-C：（1.7 ±0.6）mmol/Lvs.（3.9 ±1.6）mmol/L,P〈0.01;hs-CRP：（1.4 ±0.5）mmol/L vs.（3.8 ±1.2）mg/L,P 〈0.01],MACE were less（15.6% vs.37.1%,P =0.032）. Conclusion Early statin on patient with coronary heart disease and diametes ,though normal lipids ,which can down-regulate main adverse cardiac events significantly . Key words: Statin; coronary heart disease ; diametes ; LDL-C ; hs-CRP;

Update on the efficacy of statin treatment in acute coronary syndromes

The natural history of atherosclerosis might involve coronary plaque rupture/erosion, thrombus formation and vessel lumen occlusion, clinically recognized as acute coronary syndrome (ACS). International guidelines strongly recommend early statin administration in patients admitted for ACS. In addition to lowering circulating levels of low-density lipoprotein cholesterol (LDL-c), statin treatment was shown to promote plaque stabilization or regression in several ways, including reduction in necrotic lipid core, anti-inflammatory effects and improvement in endothelial function. The aim of this review is to summarize clinical evidence on the role of statins in secondary prevention of ACS. This narrative review is based on the material found on medline and pubmed up to August 2013. We looked for the terms 'statin, acute coronary syndromes' in combination with 'atherosclerosis, acute myocardial infarction, pathophysiology'. This review article emphasizes the relevance of the timing of statin administration to improve the outcomes after ACS. Early and continuous statin administration has emerged as key features to prevent adverse events, especially in patients admitted for ACS undergoing percutaneous coronary intervention. Clinical trials matching the improved clinical outcome with the imaging of atherosclerotic plaque stabilization/regression, further supporting the effectiveness of statin therapy. However, the achievement of these goals requires high dose of statins, thus increasing the risk of adverse events. Although clinical trials and meta-analyses have provided conflicting results, it is likely that in clinical practice, the rate of adverse events is higher, so that many concerns still remain about a statin high-dose approach in ACS patients.

Efficacy of Early Intensive Rosuvastatin Therapy in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (ROSEMARY Study)

The purpose of the study was to investigate whether early high-dose potent statin therapy in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention can reduce infarct size compared with conventional low-dose statin therapy. In a randomized placebo-controlled multicenter trial, 185 patients were assigned either to an early high-dose rosuvastatin group (n= 92, rosuvastatin 40mg before treatment plus maintenance for 7days) or to a conventional low-dose rosuvastatin group (n= 93, placebo before treatment plus rosuvastatin 10-mg maintenance for 7days). Serial cardiac magnetic resonance imaging (MRI) was performed during the acute (3 to 7days) and chronic (3months) phases. The primary end point was relative infarct volume assessed by MRI at 3months. Baseline characteristics were similar between the 2 groups, except hypertension, which was more prevalent in the high-dose group. Serial MRI data were available for 121 patients (high-dose group n= 54 and low-dose group n= 67). The relative infarct volumes in the acute (23.0 ± 9.5% vs 20.5 ± 11.7%, p= 0.208) and chronic (15.9 ± 8.3% vs 15.8 ± 9.7%, p= 0.943) phases were not different between the groups. No differences between groups were observed for periprocedural microvascular circulation evaluated by Thrombolysis In Myocardial Infarction flow grade, myocardial blush grade, ST-segment resolution, microvascular obstruction on cardiac MRI, or clinical outcomes. In conclusion, early high-dose rosuvastatin therapy in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention did not improve periprocedural myocardial perfusion or reduce infarct volume measured by MRI compared with the conventional low-dose rosuvastatin regimen.

Effect of Chronic Statin Treatment on Vascular Remodeling Determined by Intravascular Ultrasound in Patients With Acute Myocardial Infarction

Early statin treatment of patients with acute coronary syndrome results in vascular changes and improved clinical outcomes. However, the influence of chronic statin treatment on the culprit vessel in acute coronary syndrome is not fully understood. The aim of this study was to investigate the morphologic features of the culprit vessel in acute myocardial infarction by comparing patients with and without chronic statin treatment. We enroled consecutive patients with AMI, who had hyperlipidemia and primary percutaneous coronary intervention guided by intravascular ultrasound within 24 hours of symptom onset. Of 155 patients, 73 patients were stratified to the chronic statin group and 82 to the nonstatin group. Intravascular ultrasound in both the groups showed that positive remodeling was significantly less frequent in the chronic statin group (46.6%) compared with the nonstatin group (70.7%; p = 0.001). Necrotic core area was significantly smaller in the chronic statin group (2.2 ± 1.3 mm(2)) compared with the nonstatin group (3.2 ± 2.1 mm(2); p <0.001). Multivariate logistic regression analysis revealed that chronic statin treatment was significantly associated with less positive remodeling (odds ratio 0.283, 95% confidence interval 0.111 to 0.723, p = 0.008). In conclusion, chronic statin treatment reduced positive remodeling in the culprit lesions of patients with acute myocardial infarction.

Early statin therapy reduces all-cause mortality in acute hemorrhagic stroke patients without prior statin use

Early statin therapy reduces all-cause mortality in acute hemorrhagic stroke patients without prior statin use

Retraction

Clinical CardiologyVolume 36, Issue 8 p. 494-494 RetractionFree Access Retraction This article retracts the following: Retracted: The Effect of Early and Intensive Statin Therapy on Ventricular Premature Beat or Nonsustained Ventricular Tachycardia in Patients With Acute Coronary Syndrome Xian-Zhi He, Sheng-Hua Zhou, Xin-Hong Wan, Hai-Yu Wang, Qing-Hua Zhong, Jian-Fang Xue, Volume 34Issue 1Clinical Cardiology pages: 59-63 First Published online: December 10, 2010 First published: 12 August 2013 https://doi.org/10.1002/clc.22174AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat The following article from Clinical Cardiology, “The Effect of Early and Intensive Statin Therapy on Ventricular Premature Beat or Nonsustained Ventricular Tachycardia in Patients With Acute Coronary Syndrome,”1 by Xian-Zhi He, MD; Sheng-Hua Zhou, MD; Xin-Hong Wan, MD; Hai-Yu Wang, MD; Qing-Hua Zhong, MD; and Jian-Fang Xue, MD, published online on December 10, 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Dr. A.J. Camm, and Wiley Periodicals, Inc. The retraction has been agreed due to significant overlap with a similar article2 previously published by the same authors in the Cardiology Journal. References 1He X.-Z., Zhou S.-H., Wan X.-H., Wang H.-Y., Zhong Q.-H. and Xue J.-F. The effect of early and intensive statin therapy on ventricular premature beat or nonsustained ventricular tachycardia in patients with acute coronary syndrome. Clin Cardiol. 34(1): 59– 63. doi: 10.1002/clc.20818 Wiley Online LibraryWeb of Science®Google Scholar 2He XZ, Zhou SH, Wan XH, Wang HY, Zhong QH, Xue JF. The effect of early and intensive statin therapy on ventricular premature beat or non-sustained ventricular tachycardia in patients with acute coronary syndrome. Cardiol J. 2010; 17(4): 381– 385. PubMedWeb of Science®Google Scholar Volume36, Issue8August 2013Pages 494-494 ReferencesRelatedInformation

Design and baseline data of a pediatric study with rosuvastatin in familial hypercholesterolemia

Statin therapy is recommended for children with familial hypercholesterolemia (FH), but most children do not reach treatment targets. Here we present the design and results at baseline of the ongoing CHARON study, to evaluate the safety and efficacy of rosuvastatin. This study comprises an international 2-year open label, titration-to-goal study in 198 children with heterozygous FH aged 6 to 18 years, with rosuvastatin in a maximum dose of 10 mg (<10 years of age) or 20 mg (older children). In addition, 64 unaffected siblings were enrolled as controls. The primary efficacy outcome is the change from baseline in low-density lipoprotein cholesterol, and the secondary outcome is the change in carotid intima-media thickness (c-IMT) in patients with FH compared with their siblings. The primary safety outcomes are growth and sexual maturation; secondary outcomes are the change in other lipoprotein levels and the incidence of adverse events, discontinuation rates, and abnormal laboratory values. At baseline, mean age of patients with FH was 12.1 ± 3.3 years, 44% were boys, and mean low-density lipoprotein cholesterol levels were 6.1 ± 1.3 mmol/L (235.9 ± 48.7 mg/dL). Mean c-IMT was 0.399 mm (95% CI, 0.392-0.406 mm) in children with FH versus 0.377 (95% CI, 0.366-0.388 mm) in unaffected siblings (P = .001). At baseline, as expected according to on previous observations, children with FH proved to have a greater c-IMT than their healthy siblings. These differences had already occurred at a very young age, which emphasizes the importance of considering early statin initiation in this high-risk population.

Impact of early statin therapy in patients with ischemic stroke or transient ischemic attack

Statin therapy has demonstrated benefits in ischemic stroke patients. However, little is known about whether the timing of statin initiation affects clinical outcomes. The possible association of statin use and cerebral hemorrhage is also a concern for early statin therapy after stroke. The objective of this study was to evaluate the efficacy and safety of the initiation timing of statins in acute ischemic stroke. A cohort study was performed using 5-year National Health Insurance Research Database in Taiwan. Patients without prior statin therapy admitted for their new ischemic stroke or transient ischemic attack (TIA) were enrolled. Patients were recognized as inhospital use group (2019 patients, statin initiation during hospitalization), intermediate use group (2266 patients, statin initiation within 1 year after discharge) or late use group (2958 patients, statin initiation 1 year later after discharge). The study endpoint was the composite outcome of ischemic stroke, TIA, hemorrhagic stroke, or acute coronary event. As compared with inhospital use, patients with late use had a 49% increased risk (adjusted HR: 1.49, 95% CI: 1.26-1.76) of composite endpoint. In contrast, patients with intermediate use had similar risk of endpoint as those with inhospital use. The risk of cerebral hemorrhage was similar in patients receiving inhospital, intermediate, or late statin treatment. In acute ischemic stroke, patients receiving late statin treatment carried a poorer clinical outcome than those with earlier statin initiation. Inhospital statin use after an acute ischemic stroke did not increase the risk of cerebral hemorrhage.

Effect of pre-procedural statin therapy on myocardial no-reflow following percutaneous coronary intervention: a meta analysis

Background Successful revascularization of coronary artery disease, especially ST-elevation myocardial infarction (STEMI), does not always mean optimal myocardial reperfusion in a portion of patients because of no-reflow phenomenon. We hypothesized that statins might attenuate the incidence of myocardial no-reflow when used before percutaneous coronary intervention (PCI). The purpose of this study was to summarize the evidence of pre-procedural statin therapy to reduce myocardial no-reflow after PCI. Methods We searched the MEDLINE, Cochrane, and clinicaltrials.gov databases from inception to October 2012 for clinical trials that examined statin therapy before PCI. We required that studies initiated statins before PCI and reported myocardial no-reflow. A DerSimonian-Laird model was used to construct random-effects summary risk ratios. Results In all, 7 studies with 3086 patients met our selection criteria. The use of pre-procedural statins significantly reduced post-procedural no-reflow by 4.2% in all PCI patients (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.35 to 0.90, P=0.016), and attenuated by 5.0% in non-STEMI patients (RR 0.41, 95% CI 0.18 to 0.94, P=0.035). This benefit was mainly observed in the early or acute intensive statin therapy populations (RR 0.43, 95% CI 0.26 to 0.71, P=0.001). Conclusions Acute intensive statin therapy before PCI significantly reduces the hazard of post-procedural no-reflow phenomenon. The routine use of statins before PCI should be considered.

A review of statin use in patients with acute coronary syndrome in Western and Japanese populations

Early high-dose statin therapy to reduce low-density lipoprotein cholesterol (LDL-C) is associated with improved cardiovascular outcomes in Western patients with stable coronary heart disease or acute coronary syndromes (ACS), but many patients remain undertreated and do not attain LDL-C treatment goals. Early statin therapy has also been shown to improve cardiovascular outcomes in Japanese patients with ACS, and pretreatment with high-dose statin prior to percutaneous coronary intervention has been shown to reduce cardiovascular events in these patients. As is the case in Western populations, many Japanese patients may be undertreated and a residual cardiovascular risk remains. While differences in treatment practice, dosing and genetic factors exist between Japan and Western countries, similarities are also evident when Japanese statin studies are compared with those performed in Western populations. With the increasing prevalence of cardiovascular risk factors in Japan, aggressive statin treatment may be beneficial in achieving optimal cardiovascular outcomes.

Cholesterol levels and the association of statins with in-hospital mortality of myocardial infarction patients insights from a Chilean registry of myocardial infarction.

Hypercholesterolemia is a strong risk factor for myocardial infarction (MI). There is scarce information regarding lipoprotein levels among patients with MI in Latin America as well as about the association of very early statin therapy during the course of acute MI. Very early statin prescription might be associated with a reduction on in-hospital mortality in MI patients with nearly normal lipid levels. Prospective registry database analysis of MI patients admitted between 2001 and 2007 at a single university hospital from which demographics, treatments, clinical variables, and mortality were assessed. Patients naïve to statin therapy were divided in 2 groups, according to whether they received (group A) or did not receive (group B) statins during the first 24 hours after admission. In the 1465 patients analyzed, mean plasma levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) were 197, 117, and 44 mg/dL, respectively, and 41.8% had HDL-C ≤40 mg/dL. Among statin naïve patients (n = 1272), 67% were classified in group A and 33% in group B. Overall in-hospital mortality was 4.1%: 1.8% in group A and 8.5% in group B. In the multivariate analysis, including propensity score for statin prescription, the odds ratio for in-hospital mortality for group A was 0.971 (95% confidence interval: 0.944-0.999, P = 0.04). In the Chilean registry of MI patients, low HDL-C was the main lipid disturbance. Very early statin use after MI appears to be associated with a borderline significant and independent reduction of in-hospital mortality.

STATINS LOADING BEFORE PCI ON STEMI

Early statin loading before coronary angiography has shown to reduce ischemic complications in patients undergoing PCI in the course of ACS, and to improve indices of reperfusion in STEMI patients undergoing primary PCI (PPCI) in small prospective randomized studies. The purpose of this study was to

Fish Oils, Coronary Heart Disease, and the Environment

Clinical trials continue to produce conflicting results on the effectiveness of fish oils for the primary and secondary prevention of coronary heart disease. Despite many large, well-performed studies, questions still remain, made even more complex by the addition of early revascularization and statins in our coronary heart disease armamentarium. This is complicated by the reality that fish oil production has a measureable impact on reducing fish populations, which in turn has a negative impact on creating a sustainable product. We review the current data for fish oil usage in the primary and secondary prevention of coronary heart disease with an eye toward future studies, and the effects fish oil production has on the environment and efforts that are currently under way to mitigate these effects.

Evaluation of Serial Changes in Tissue Characteristics During Statin-Induced Plaque Regression Using Virtual Histology-Intravascular Ultrasound Studies

Treatment of all coronary arteries is important to improve the prognosis of acute coronary syndrome after early reperfusion of the culprit lesion. Early statin treatment has been reported to cause regression of plaques away from the site of the culprit lesion in patients with acute coronary syndrome. However, the precise mechanism of coronary plaque regression is not well understood. We studied the effects of statins on the regression of coronary plaques away from the culprit lesions in 120 patients with acute coronary syndrome. We used virtual histology-intravascular ultrasound studies to evaluate nonpercutaneous coronary intervention lesions at admission and short-term (2 to 3 weeks) and medium-term (8 to 10 months) follow-up. According to the medium-term evaluation findings, the subjects were divided into 2 groups: a plaque regression group (n = 94) and a plaque progression group (n = 26). In the regression group, the fibrofatty component had decreased at the short-term (-20.0% vs baseline) and had decreased further at the medium-term (-26.7%) evaluations. The fibrous component had also decreased at the short-term (-5.1%) and medium-term (-8.5%) evaluations. In contrast, the necrotic core component showed a tendency to increase in the short term (+12.5%) but then decreased at the medium-term evaluation (-6.3%). In the progression group, the fibrofatty and fibrous components had increased at the short-term (+37.5%, +11.3%) and medium-term (+50.5%, +13.2%) evaluations; however, the necrotic core had decreased at the short-term (-19.0%) and medium-term (-23.8%) evaluations. In conclusion, regarding the course of coronary plaque regression by statin therapy, the plaques began to reduce the volume of fibrofatty and fibrous components in the early phase, associated with a transiently increased necrotic core component. Furthermore, even in the case of plaque progression, statins caused a reduction in the necrotic core.

Abstract WP60: Can Early Statin Administration in the Acute Stage of Ischemic Stroke Intensify the Effect of Thrombolysis?

Objective: We aimed to determine whether early statin use improves functional outcome and reduces post-thrombolytic symptomatic intracerebral hemorrhage (sICH) in acute symptomatic steno-occlusion of major cerebral arteries. Method: Using a prospective stroke registry, we identified a consecutive series of 337 patients who arrived within 6 h of stroke onset, had symptomatic stenosis (&gt;50%) or occlusion, received thrombolysis, and were followed up at 3 months. We compared the 3-month modified Rankin Scale (mRS) score and sICH incidence during hospitalization according to post-thrombolytic statin use. Statin use was categorized into early use (≤1 day of onset; EU), late use (&gt; 1 day of onset, LU), and no use (NU). sICH was defined as type-2 parenchymal hemorrhage with a more than 4 point decrease in NIHSS or death. Result: The patients’ mean age was 6e8.8 years (55.8% males; median baseline NIHSS, 13). Thrombolysis modalities were as follows: intravenous only (25.5%), intra-arterial only (31.2%), and combined (43.4%). EU was 34.1% (N = 115); LU, 15.4% (N = 52); and NU, 50.4% (N = 170). Percentages of favorable outcome (mRS, 0-1) differed significantly by statin use (39.1% in EU, 34.6% in LU, and 22.4% in NU; P = 0.007); sICH rates also differed (2.6%, 0.0%, and 10.0%, respectively; P = 0.005). Multivariable analyses showed an independent increase in the odds of favorable outcome and decrease in those of sICH after early stain use (Figure). Conclusion: Early statin use may improve functional outcome and reduce the occurrence of post-thrombolytic sICH.

Relationship between Advanced Glycation End Products and Plaque Progression in Patients with Acute Coronary Syndrome: The JAPAN-ACS Sub-study

BackgroundThe Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial demonstrated that early aggressive statin therapy in patients with ACS significantly reduces plaque volume (PV). Advanced glycation end products (AGEs) and the receptors of AGEs (RAGE) may lead to angiopathy in diabetes mellitus (DM) and may affect on the development of coronary PV. The present sub-study of JAPAN-ACS investigates the association between AGEs and RAGE, and PV.MethodsIntravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment (either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin), in patients with ACS. In the 208 JAPAN-ACS subjects, PV using IVUS in non-culprit segment > 5 mm proximal or distal to the culprit lesion and, serum levels of AGEs and soluble RAGE (sRAGE) were measured at baseline and 8–12 months after PCI.ResultsAt baseline, no differences in the levels of either AGEs or sRAGE were found between patients with DM and those without DM. The levels of AGEs decreased significantly with statin therapy from 8.6 ± 2.2 to 8.0 ± 2.1 U/ml (p < 0.001), whereas the levels of sRAGE did not change. There were no significant correlations between changes in PV and the changes in levels of AGEs as well as sRAGE. However, high baseline AGEs levels were significantly associated with plaque progression (odds ratio, 1.21; 95% confidence interval, 1.01 - 1.48; p = 0.044) even after adjusting for DM in multivariate logistic regression models.ConclusionsHigh baseline AGEs levels were associated with plaque progression in the JAPAN-ACS trial. This relationship was independent of DM. These findings suggest AGEs may be related to long-term glucose control and other oxidative stresses in ACS.Trial registrationNCT00242944

Effect of Early Statin Treatment in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction

Background and ObjectivesThe benefit of early statin treatment following acute myocardial infarction (MI) complicated with cardiogenic shock (CS) has not been well studied. We sought to assess the effect of early statin therapy in patients with CS complicating acute MI.Subjects and MethodsWe studied 553 statin-naive patients with acute MI and CS (Killip class IV) who underwent revascularization therapy between November 2005 and January 2008 at 51 hospitals in the Korea Acute Myocardial Infarction Registry. Patients were divided into 2 groups: those who received statins during hospitalization (n=280) and those who did not (n=273). The influence of statin treatment on a 12-month clinical outcome was examined using a matched-pairs analysis (n=200 in each group) based on the propensity for receiving statin therapy during hospitalization.ResultsBefore adjustment, patients receiving statin, compared to those not receiving statin, had a more favorable clinical profile, were less likely to suffer procedural complications, and more likely to receive adequate medical therapy. Patients receiving statin had lower unadjusted in-hospital mortality and composite rate of mortality, MI, and repeat revascularization at 12 months, which remained significantly lower after adjustment for patient risk, procedural characteristics, and treatment propensity.ConclusionIn CS patients with acute MI undergoing revascularization therapy, early statin treatment initiated during hospitalization was associated with lower rates of in-hospital death and 12-month adverse cardiac events.