Early Statin Treatment Research Articles

Abstract 91: Early Stroke Recurrence Is Not Reduced By Early Statin Initiation In The Point Trial Population

Objective: To discern effects of early statin treatment on early stroke recurrence in the POINT trial. Background: Benefits of statin therapy in reducing risk of ischemic stroke over the long-term are well-established, but the immediate effects of statin therapy on early stroke recurrence after an initial ischemic event are less clear. Design/Methods: In secondary analysis of the data of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, we evaluated the effects of statins on early stroke recurrence within 7 days of randomization using Cox proportional hazard regression analysis. We separately compared the effects in subgroups of subjects on and not on statins prior to the index event. Results: In the POINT trial, most recurrences of ischemic stroke were early, with 175 occurring within 7 days of trial entry, and only 105 occurring over the remainder of the 90 day trial. Overall, 39% were on statin treatment at time of enrollment which increased to 79% by 7 days post-index event. In Cox proportional hazard analysis for stroke recurrence over the 7 day period after index stroke or TIA, statin administration showed no significant effect in subjects not on statin at baseline (Adjusted p=0.34). In contrast, statin use prior to enrollment was associated with decreased hazard of early stroke recurrence (Adjusted H.R. 0.31, p=0.001). Conclusion: In the POINT trial population of patients with minor ischemic stroke or TIA, prior treatment with statins was associated with decreased risk of early stroke recurrence within 7 days following index stroke or TIA. There was no effect of initiating statin treatment in reducing risk of early stroke recurrence.

Mathematical modelling of the effects of statins on the growth of necrotic core in atherosclerotic plaque

A large necrotic core increases the risk of atherosclerotic plaque instability. Statins can delay the growth of necrotic core in plaques, but the kinetic mechanism of statins in slowing down the necrotic core has not yet been addressed in detail. In this paper, a mathematical model is governed by a system of advection-diffusion-reaction equations coupling of the porous nature of vessel wall is established and applied to illustrate the plaque growth with lipid-rich necrotic core (LRNC) with and without statins using finite element method. We study the influence of LRNC plaque growth for different drug concentrations at different time intervals. The results showed that the drug use at different time points has a significant impact on the treatment efficacy. Compared with short-term, low-dose treatment, early statin treatment with high dose showed more pronounced effects on reducing the low-density lipoprotein (LDL) cholesterol, decreasing the volume of necrotic core, changing the characteristics of plaques, and improving the plaque stability. The model is validated by comparing with the clinical data, and may be used to predict the progression of LRNC plaque and the effects of statin therapy.

Lipoprotein particle sizes in patients undergoing kidney transplantation.

Asymptomatic atherosclerotic disease is prevalent in the middle-aged group of kidney transplant recipients. In order to improve the estimation of their cardiovascular risk, dyslipidaemia pattern is very important to be evaluated. Knowledge of the lipid particle spectrum in patients undergoing kidney transplantation could help the clinicians to timely start intervention and prevention of atherosclerosis with an early hypolipidemic statin treatment (Tab. 2, Ref. 20).

Chronic statin treatment is a predictor of pre-interventional infarct-related artery patency in patients with ST elevation myocardial infarction treated with percutaneous coronary intervention.

Beyond lipid-lowering effects, early statin treatment has beneficial effects on prognosis after acute coronary syndrome. Infarct-related artery (IRA) patency before percutaneous coronary intervention (PCI) is known to be a strong pre-dictor of improved clinical outcome. We aimed to investigate the effects of chronic statin treatment before admission on IRA patency after myocardial infarction. In this study, 938 ST elevation myocardial infarction (STEMI) patients admitted to the hospital within the first 12 h of symptom onset were prospectively enrolled (male, n = 682; female, n = 256; mean age 58.6 ± 12.4 years). All patients underwent emergent primary PCI. Patients were divided into two groups based upon angiographic IRA patency. Impaired IRA patency was defined as Thrombolysis In Myocardial Infarction (TIMI) grade 0 and 1 flow (non-patent IRA group). Angiographic IRA patency was defined as TIMI 2 and 3 flow (patent IRA group). Previous statin usage was more frequent in the patent IRA group (n = 138; 71.9%), than in the non-patent IRA group (n = 110; 14.7%; p < 0.001). Pre-PCI IRA patency was independently associated with body mass index (odds ra-tio [OR] = 1.087, 95% confidence interval [CI] 1.005-1.176, p < 0.001), previous chronic statin use (OR 0.065, 95% CI 0.043-0.098, p = 0.039), ejection fraction (OR 1.041, 95% CI 1.018-1.064, p < 0.001), and SYNTAX score (OR 0.927, 95% CI 0.899-0.957, p < 0.001) in multivariate logistic regression analysis. Chronic pre-treatment with statins is a significant predictor of the IRA patency in patients with STEMI.

Effects of Intensive Statin Therapy on Left Ventricular Function in Patients with Myocardial Infarction and Abnormal Glucose Tolerance

Objectives: Abnormal glucose tolerance in patients with acute myocardial infarction (AMI) is associated with greater mortality and adverse cardiovascular effects. As statins possess a range of beneficial pleiotropic effects on the cardiovascular system, we sought to assess the cardioprotective effects of statins on left ventricular function in patients with AMI in relation to glycometabolic state. Methods: In a prospective, randomized trial, 140 patients with AMI were randomized to intensive statin therapy receiving statin loading with 80 mg of rosuvastatin followed by 40 mg daily or standard statin therapy. Patients were assessed with an oral glucose tolerance test and their left ventricular (LV) function was assessed with speckle-tracking echocardiography measuring regional longitudinal systolic strain (RLSS) in the infarct area. Results: Overall RLSS in the infarct area improved by a mean (±SD) of -4.22% (±5.19) in the intensive-care group and -2.48% (±4.01) in the usual-care group after 1 month (p = 0.047). In patients with abnormal glucose tolerance, RLSS improved by -5.01% (±5.28) in the intensive-care group and -2.15% (±4.22) in the usual-care group (p = 0.01). Conclusions: Early high-dose statin treatment improved RLSS in the infarct area in patients with AMI, and a trend of greater improvement was seen in patients with abnormal glucose tolerance.

Abstract 11806: Early, Intensive Atorvastatin Treatment Reduces First and Recurrent Hard Cardiovascular Events After Acute Coronary Syndrome

Background: Early, intensive statin treatment is standard of care after acute coronary syndrome (ACS), but only one placebo (PBO)-controlled trial has demonstrated an early benefit of such treatment. In the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial, the primary outcome of time to first occurrence of death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina (UA) was reduced with atorvastatin (ATV) 80 mg/day, compared with PBO. However, this result was borderline significant (HR 0.84, 95% CI 0.70-1.00, p=0.048) and driven largely by reduced UA, leading some to argue that early intensive statin treatment does not modify early “hard” events after ACS. On the other hand, the efficacy of an intervention after ACS is only partially accounted for by time to first event because patients may experience multiple events of similar importance, especially when competing risk for death is relatively low. Objective: In a post-hoc analysis of MIRACL, we evaluated the efficacy of ATV to reduce total (first and recurrent) hard cardiovascular events after ACS. Hard events were defined as death, MI, stroke, and resuscitated cardiac arrest. Methods: 3086 patients were randomly assigned to treatment with ATV or PBO, beginning 1-4 days after ACS and continuing for 16 weeks. Time to first event was assessed by Cox regression. Total events were analyzed by Cox regression with model-based variance estimation to determine correlation between events within a subject. Results: ATV did not significantly reduce time to first hard event (HR 0.89, 95% CI 0.72-1.11, P=0.27), but did significantly reduce total hard events ( Table ). To prevent 1 hard event, only 10.6 patient-years of treatment with ATV were required. The HR for total events was minimally affected by inclusion or exclusion of UA. Conclusion: Intensive treatment with ATV reduces total hard events over 16 weeks following ACS, and is an efficient secondary prevention intervention.

A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles.

BackgroundCumulative evidence indicates that statins induce myotoxicity. However, the lack of understanding of how statins affect skeletal muscles at the structural, functional, and physiological levels hampers proper healthcare management. The purpose of the present study was to investigate the early after-effects of lovastatin on the slow-twitch soleus (Sol) and fast-twitch extensor digitorum longus (EDL) muscles.MethodsAdult C57BL/6 mice were orally administrated with placebo or lovastatin [50 mg/kg/d] for 28 days. At the end of the treatment, the isometric ex vivo contractile properties of the Sol and EDL muscles were measured. Subtetanic and tetanic contractions were assessed and contraction kinetics were recorded. The muscles were then frozen for immunohistochemical analyses. Data were analyzed by two-way ANOVA followed by an a posteriori Tukey’s test.ResultsThe short-term lovastatin treatment did not induce muscle mass loss, muscle fiber atrophy, or creatine kinase (CK) release. It had no functional impact on slow-twitch Sol muscles. However, subtetanic stimulations at 10 Hz provoked greater force production in fast-twitch EDL muscles. The treatment also decreased the maximal rate of force development (dP/dT) of twitch contractions and prolonged the half relaxation time (1/2RT) of tetanic contractions of EDL muscles.ConclusionsAn early short-term statin treatment induced subtle but significant changes in some parameters of the contractile profile of EDL muscles, providing new insights into the selective initiation of statin-induced myopathy in fast-twitch muscles.

Prediction and prevention of hypertensive disorders of pregnancy.

The most common classifications of hypertensive disorders of pregnancy consist of chronic hypertension, gestational hypertension, preeclampsia (PE) and superimposed PE. A common final pathophysiology of PE is endothelial dysfunction. The most successful translational research model for explaining the cause-effect relationship in the genesis of PE is the angiogenic/angiostatic balance theory, involving soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and soluble endoglin (sEng). In a systematic review of articles on the prediction of early-onset PE using angiogenesis-related factors, we revealed that the prediction of early-onset PE in the first trimester is clinically possible, but the prediction of early-onset PE in the early third trimester might be ideal. In addition, an onset threshold or a serial approach appeared to be clinically useful for predicting the imminent onset of PE, with onset at <4 weeks after blood sampling in the second and early third trimesters, because the positive likelihood ratio was >10 and the positive predictive value was >20%. The National Institute for Health and Care Excellence guidelines state that the Triage PlGF testing and Elecsys immunoassay for the sFlt-1/PlGF ratio could help to exclude PE in women with suspected PE at 20-34 weeks of gestation. Until now, we have not found any effective therapies to prevent PE. However, low-dose aspirin treatment starting at ⩽16 weeks of gestation might be associated with a marked reduction in PE. In addition, early statin treatment might prevent the occurrence of PE. Currently, a clinical trial using pravastatin for the prevention of PE is ongoing.

GPi vs STN deep brain stimulation for Parkinson disease: Three-year follow-up.

Editors' Note: In reference to “GPi vs STN deep brain stimulation for Parkinson disease: Three-year follow-up,” Drs. Sidiropoulos and LeWitt suggest that the study findings could be due to suboptimal globus pallidus internus (GPi) programming and targeting imprecision. Odekerken et al., authors of the study, disagree and offer several arguments to support their findings, which showed superiority of subthalamic nucleus (STN) over GPi deep brain stimulation. Commenting on “Statin pretreatment is associated with better outcomes in large artery atherosclerotic stroke,” Dr. Goldstein further discusses the benefit of statin on cerebrovascular events and functional outcome, citing 2 exploratory analyses based on data from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Tsivgoulis et al., authors of the study, suggest further research to establish the safety and efficacy of early statin treatment on the …

Development of Human-Like Advanced Coronary Plaques in Low-Density Lipoprotein Receptor Knockout Pigs and Justification for Statin Treatment Before Formation of Atherosclerotic Plaques.

BackgroundAlthough clinical trials have proved that statin can be used prophylactically against cardiovascular events, the direct effects of statin on plaque development are not well understood. We generated low‐density lipoprotein receptor knockout (LDLR −/−) pigs to study the effects of early statin administration on development of atherosclerotic plaques, especially advanced plaques.Methods and Results LDLR −/− pigs were generated by targeted deletion of exon 4 of the LDLR gene. Given a standard chow diet, LDLR −/− pigs showed atherosclerotic lesions starting at 6 months of age. When 3‐month‐old LDLR −/− pigs were fed a high‐cholesterol, high‐fat (HCHF) diet for 4 months (HCHF group), human‐like advanced coronary plaques developed. We also fed 3‐month‐old LDLR −/− pigs an HCHF diet with pitavastatin for 4 months (Statin Prophylaxis Group). Although serum cholesterol concentrations did not differ significantly between the 2 groups, intravascular ultrasound revealed 52% reduced plaque volume in statin‐treated pigs. Pathological examination revealed most lesions (87%) in the statin prophylaxis group were early‐stage lesions, versus 45% in the HCHF diet group (P<0.01). Thin‐cap fibroatheroma characterized 40% of the plaques in the HCHF diet group versus 8% in the statin prophylaxis group (P<0.01), intraplaque hemorrhage characterized 11% versus 1% (P<0.01), and calcification characterized 22% versus 1% (P<0.01).ConclusionsResults of our large animal experiment support statin prophylaxis before the occurrence of atherosclerosis. Early statin treatment appears to retard development of coronary artery atherosclerosis and ensure lesion stability. In addition, the LDLR −/− pigs we developed represent a large animal model of human‐like advanced coronary plaque suitable for translational research.

Early Use of Statin in Patients Treated with Alteplase for Acute Ischemic Stroke.

Studies have reported that statin usage before stroke can increase the incidence of intracerebral hemorrhage after thrombolytic treatment. However, whether the administration of statin at an early stage of ischemic stroke increases hemorrhage occurrence is unknown. The aim of this study was to assess the effect of statin on neurological imaging and functional outcomes after intravenous alteplase treatment, within 24 h of acute ischemic stroke attack. A total of 119 consecutive acute ischemic stroke patients treated by intravenous alteplase were recruited, of which 71 patients (59.7 %) were given statin therapy within 24 h of stroke onset. The physiological parameters, including demography, vascular risk factors, and clinical characteristics were recorded. The occurrence of intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day functional outcomes, and mortality in the patients were further analyzed. There were 24 occurrences of ICH after alteplase treatment (20.2 %) and there was no difference when patients were treated with statin (p = 0.280). Multivariate logistic regression analysis showed no significant correlation between the administration of statin and the occurrence of ICH (p = 0.230) or sICH (p = 0.949). There was a trend toward better neurological function with higher statin dose. The use of statin in the early stage of ischemic stroke is safe and does not increase the risk of intracerebral hemorrhage after alteplase treatment, suggesting that a clinical trial of early statin treatment on a large scale following thrombolysis is needed for further evaluation.

Abstract 13244: Is Early Statin Treatment Justified Before Formation of Atherosclerotic Plaques?

Objective: Although statin is recommended for secondary prevention of acute coronary syndrome regardless of the baseline LDL-cholesterol level, statin administration in the pre-intervention phase has not been established as a routine strategy because of lack of sufficient evidence. We conducted an animal study comparing the results of early statin administration vs. no such administration in pigs susceptible to atherosclerosis. Methods and Results: Three-month-old LDL receptor knockout (LDLR-/-) pigs with no atherosclerosis were divided into two groups: those fed an atherosclerotic diet consisting of 15% fat and 1.5% cholesterol for 4 months (control group) and those fed the same diet but given oral pitavastatin (40 mg/day) (early treatment group). Human-like unstable plaques developed in the coronary arteries of the control pigs. After in vivo intravascular ultrasound (IVUS) examination, pigs’ coronary arteries were harvested and cut into 1-cm sections for pathological analyses. Blood cholesterol levels (mg/dL) did not differ significantly between the control group and early treatment group: total cholesterol, 931±45 vs 881±81; VLDL, 539±26 vs 514±59; LDL, 277±35 vs 245±36; HDL, 89±3 vs 95 ± 6, respectively). IVUS and pathological examination revealed similar lumen areas but a significant reduction in plaque and vessel volume in the early treatment group. The proportion of atherosclerotic lesions was 80% in the control group and 67% in the early treatment group (P=0.01). Most lesions (87%) in the early treatment group were early-stage lesions (Stary types I-III), whereas 45% of lesions in the control group were early-stage lesions (P&lt;0.01). Only 1% of lesions were considered unstable plaques (Stary type VI lesions) in the early treatment group (vs 10% in the control group) (P&lt;0.01). With respect to instability, thin-cap fibroatheroma was 40% in the control group vs. 8% in the early treatment group (P&lt;0.01), intraplaque hemorrhage was 11% vs 1% (P&lt;0.01), and calcification was 22% vs 1% (P&lt;0.01). Conclusions: Our large-animal experiment provides support for early statin treatment before occurrence of atherosclerosis. Early statin treatment appears to retard development of coronary artery atherosclerosis and maintain lesion stability.

Effects of intensive lipid-lowering therapy on coronary plaques composition in patients with acute myocardial infarction: Assessment with serial coronary CT angiography.

Statins have been shown to possess favourable effects on the cardiovascular system with stabilization of the vulnerable plaque. We sought to assess the effects of early aggressive statin treatment on plaque composition in patients with acute myocardial infarction (AMI), using serial assessment with coronary CT-angiography (CTA). In a prospective randomized blinded endpoint trial patients with AMI were randomized to an intensive lipid lowering treatment receiving statin loading with 80mg rosuvastatin followed by 40mg daily or standard statin therapy according to current guidelines. Patients were assessed with CTA at baseline and after 12 months with evaluation of plaque volume and composition. In total, 140 patients with AMI were randomized and plaque composition was assessed in 96 patients. In the intensive care group LDL-level was median 1.3 [0.9; 1.5] mmol/l at 12 months follow-up and 2.0 [1.7; 2.4] mmol/l in the usual care group, p<0.001. Plaque volume increased over 12 months with 43.5 (±225.8) mm(3) in the intensive care group and 19.1 (±190.2) mm(3) in the usual care group, p=0.57. Plaque composition changed over 12 months with an increase in total dense calcium volume by 11.1 (±39.6) mm(3), corresponding to a 23% increase, in the intensive care group and a decreased by-0.4 (±26.6) mm(3) in the usual care group, p<0.001. Necrotic core volume increased 26.8 (±122.1) mm(3) in the intensive care group and 25.2 (±80.1) mm(3) in the usual care group, p=0.94. Early aggressive lipid lowering therapy significantly increases dense calcium volume in patients with AMI.

Statins for acute coronary syndrome.

The early period following the onset of acute coronary syndrome (ACS) represents a critical stage of coronary heart disease, with a high risk of recurrent events and deaths. The short-term effects of early treatment with statins on patient-relevant outcomes in patients suffering from ACS are unclear. This is an update of a review previously published in 2011. To assess the effects, both harms and benefits, of early administered statins in patients with ACS, in terms of mortality and cardiovascular events. We updated the searches of CENTRAL (2013, Issue 3), MEDLINE (Ovid) (1946 to April Week 1 2013), EMBASE (Ovid) (1947 to 2013 Week 14), and CINAHL (EBSCO) (1938 to 2013) on 12 April 2013. We applied no language restrictions. We supplemented the search by contacting experts in the field, by reviewing the reference lists of reviews and editorials on the topic, and by searching trial registries. Randomized controlled trials (RCTs) comparing statins with placebo or usual care, with initiation of statin therapy within 14 days following the onset of ACS, follow-up of at least 30 days, and reporting at least one clinical outcome. Two authors independently assessed risk of bias and extracted data. We calculated risk ratios (RRs) for all outcomes in the treatment and control groups and pooled data using random-effects models. Eighteen studies (14,303 patients) compared early statin treatment versus placebo or no treatment in patients with ACS. The new search did not identify any new studies for inclusion. There were some concerns about risk of bias and imprecision of summary estimates. Based on moderate quality evidence, early statin therapy did not decrease the combined primary outcome of death, non-fatal myocardial infarction, and stroke at one month (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.80 to 1.08) or four months (RR 0.93, 95% CI 0.81 to 1.06) of follow-up when compared to placebo or no treatment. There were no statistically significant risk reductions from statins for total death, total myocardial infarction, total stroke, cardiovascular death, revascularization procedures, and acute heart failure at one month or at four months, although there were favorable trends related to statin use for each of these endpoints. Moderate quality evidence suggests that the incidence of unstable angina was significantly reduced at four months following ACS (RR 0.76, 95% CI 0.59 to 0.96). There were nine individuals with myopathy (elevated creatinine kinase levels more than 10 times the upper limit of normal) in statin-treated patients (0.13%) versus one (0.015%) in the control groups. Serious muscle toxicity was mostly limited to patients treated with simvastatin 80 mg. Based on moderate quality evidence, due to concerns about risk of bias and imprecision, initiation of statin therapy within 14 days following ACS does not reduce death, myocardial infarction, or stroke up to four months, but reduces the occurrence of unstable angina at four months following ACS. Serious side effects were rare.

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.

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.

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.

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.

The importance of atrial fibrillation/flutter as a cause of ischemic stroke

Int J Cardiol 2010;144:1–2. [9] Aronow HD, Topol EJ, Roe MT, et al. Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study. Lancet 2001;357:1063–8. [10] Newby LK, Kristinsson A, Bhapkar MV, et al. Early statin initiation and outcomes in patients with acute coronary syndromes. JAMA 2002;287:3087–95. [11] Spencer FA, Allegrone J, Goldberg RJ, et al. Association of statin therapy with outcomes of acute coronary syndromes: the GRACE study. Ann Intern Med 2004;140:857–66. [12] Stenestrand U, Wallentin L. Early statin treatment following acute myocardial infarction and 1-year survival. JAMA 2001;285:430–6. [13] Fonarow GC, Wright RS, Spencer FA, et al. Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol 2005;96:611–6. [14] Pan W, Pintar T, Anton J, Lee VV, Vaughn WK, Collard CD. Statins are associated with a reduced incidence of perioperative mortality after coronary artery bypass graft surgery. Circulation 2004;110:II45–9. [15] DiNapoli P, AntonioTaccardi A, Grilli A, Spina R, FelacoM,Barsotti A, et al. Simvastatin reduces reperfusion injurybymodulatingnitric oxide synthaseexpression: anexvivo study in isolated working rat hearts. Cardiovasc Res 2001;51:283–93. [16] Lefer AM, Campbell B, Shin YK, Scalia R, Hayward R, Lefer DJ. Simvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts. Circulation 1999;100:178–84. [17] Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495–504. [18] Leeper NJ, Ardehali R, deGoma EM, Heidenreich PA. Statin use in patients with extremely low low-density lipoprotein levels is associated with improved survival. Circulation 2007;116:613–8.

AS-242 Effect of Early Statin Treatment in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction

The 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.