ECLIPSE Study Research Articles

Changes in Body Composition in Patients with Chronic Obstructive Pulmonary Disease: Do They Influence Patient-Related Outcomes?

Aims: The follow-up of the ECLIPSE study, a prospective longitudinal study to identify and define parameters that predict disease progression over 3 years in chronic obstructive pulmonary disease (COPD), allows the examination of the effect of body composition changes on COPD-related outcomes. Methods: Body composition and health status were established in 2,115 COPD patients, 327 smoking and 239 nonsmoking controls at baseline and 3 years, while mortality was recorded in year 2 and 3 in the COPD patients. Associations between fat free mass index (FFMI) and fat mass index (FMI) changes to deterioration in health status and mortality were determined. Results: Change in FFMI and FMI over 3 years was small and comparable between the groups. Underweight and obese patients had the worst health status. Worsening health status was associated with FFMI decrease in underweight patients and FMI increase in overweight/obese patients. While overweight patients had the lowest mortality, FFMI or FMI decrease was associated with a higher mortality. Conclusion: Changes in body composition over 3 years were small and comparable in COPD patients and control subjects. Nevertheless, muscle mass decline in underweight and fat mass increase in overweight/obese patients is associated with worsening health status. Overweight is associated with decreased mortality, but muscle mass and fat mass decline are detrimental for mortality.

Exacerbation history in COPD patients with and without Expiratory Flow Limitation (EFL) measured by forced oscillometry technique (FOT)

Within-breath change in reactance at 5 Hz (DX5) during tidal breathing reliably detects EFL in patients with COPD1. We used this method to determine the presence of EFL in 268 stable COPD patients from the Bergen cohort of the Eclipse study. Our aim was to examine the association between EFL and history of exacerbations. The Eclipse study was a multi-centre, three-year observational, non-interventional, case-control study with a total of 8 visits. For further characterization, see Agusti et al2. We compared the self-reported exacerbation history 12 months before visit 1 in COPD patients without EFL compared with those who experienced EFL during the duration of the study. A COPD patient with 2 or more exacerbations was defined as a frequent exacerbator. FOT measurements were performed using a Masterscreen IOS. Within-breath reactance, DX5 was estimated as mean inspiratory X5 – mean expiratory X5 over a period of 30s, and EFL defined when the mean of 3 such measurements exceeded 0.28kPa/L/s, the threshold proposed by Dellaca et al.1 We found that despite having similar levels of spirometric impairment COPD patients with an EFL≥75% of the visits had a significantly worse exacerbation history and a much higher percentage of frequent exacerbators than those without EFL. In GOLD stage 2 those with frequent flow limitation had a considerably higher exacerbation history while there was little difference between the non-EFL and those with EFL<75% of the visits. The presence of EFL at rest may be a useful way to identify patients at greater risk of these events.

Economic Assessment of Home-Based COPD Management Programs

Home-based exacerbation management programs have been proposed as an approach to reducing the clinical and financial burden of COPD. We demonstrate a framework to evaluate such programs in order to guide program design and performance decisions towards optimizing cost and clinical outcomes. This study models the impact of hypothetical exacerbation management programs through probabilistic Markov simulations. Patients were stratified by risk using exacerbation rates from the ECLIPSE study and expert opinion. Three scenarios were modeled, using base, worst and best case parameters to suggest potential telehealth program performance. In these scenarios, acute exacerbations could be detected early, with sensitivity and specificity ranging from 60–90%. Detected acute exacerbations could be diverted to either a sub-acute pathway (12.5–50% probability), thus entirely avoiding hospitalization, or a lower cost pathway through length-of-stay reduction (14–28% reduction). For a cohort of patients without prior hospitalization, the base case telehealth scenario results in a cumulative per-patient lifetime savings of $2.9K over ∼12 years. For a higher risk cohort of patients with a prior admission and 1 to 2 acute exacerbations per year, a cumulative $16K per patient was saved during the remaining ∼3 life-years. Acceptable prices for home-based exacerbation detection testing were highly dependent on patient risk and scenario, but ranged from $290–$1263 per month for the highest risk groups. These results suggest the economic viability of exacerbation management programs and highlight the importance of risk stratification in such programs. The presented model can further be adapted to model specific programs as trial data becomes available.

Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort

Comorbidities, are common in COPD, have been associated with poor outcomes and are thought to relate to systemic inflammation. To investigate comorbidities in relation to systemic inflammation and outcomes we recorded comorbidities in a well characterized cohort (ECLIPSE study) for 2164 clinically stable COPD subjects, 337 smokers and 245 non-smokers with normal lung function. COPD patients had a higher prevalence of osteoporosis, anxiety/panic attacks, heart trouble, heart attack, and heart failure, than smokers or nonsmokers. Heart failure (Hazard Ratio [HR] 1.9, 95% Confidence Interval [CI] 1.3-2.9), ischemic heart disease (HR 1.5, 95% CI 1.1-2.0), heart disease (HR 1.5, 95% CI 1.2-2.0), and diabetes (HR 1.7, 95% CI 1.2-2.4) had increased odds of mortality when coexistent with COPD. Multiple comorbidities had accumulative effect on mortality. COPD and cardiovascular disease was associated with poorer quality of life, higher MRC dyspnea scores, reduced 6MWD, higher BODE index scores. Osteoporosis, hypertension and diabetes were associated with higher MRC dyspnea scores and reduced 6MWD. Higher blood concentrations of fibrinogen, IL-6 and IL-8 levels occurred in those with heart disease. Comorbidity is associated with poor clinical outcomes in COPD. The comorbidities of heart disease, hypertension and diabetes are associated with increased systemic inflammation.

Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort.

The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifies patients with chronic obstructive pulmonary disease (COPD) into four groups (A to D). We explored the characteristics, stability and relationship to outcomes of these groups within the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) (n = 2101). Main results showed that: 1) these groups differed in several clinical, functional, imaging and biological characteristics in addition to those used for their own definition; 2) A and D groups were relatively stable over time, whereas groups B and C showed more temporal variability; 3) the risk of exacerbation over 3 years increased progressively from A to D, whereas that of hospitalisation and mortality were lowest in A, highest in D and intermediate and similar in B and C, despite the former having milder airflow limitation. The prevalence of comorbidities and persistent systemic inflammation were highest in group B. The different longitudinal behaviour of group A versus B and C versus D (each pair with similar forced expiratory volume in1 s (FEV1) values supports the 2011 GOLD proposal of assessing COPD patients by more than FEV1 only. However the assumption that symptoms do not equate to risk appears to be naïve, as groups B and C carry equally poor clinical outcomes, though for different reasons.

Chronic Obstructive Pulmonary Disease: More Imaging, More Phenotyping...Better Care?

Chronic Obstructive Pulmonary Disease: More Imaging, More Phenotyping...Better Care?

Systemic Biomarkers in the Evaluation and Management of COPD Patients: Are We Getting Closer to Clinical Application?

Chronic obstructive pulmonary disease (COPD) is a complex, multicomponent disease at the clinical, cellular, and molecular levels. Over the past few years there has been a growing interest in the field of biomarkers in COPD and a large number of studies have evaluated potential candidate molecules in different patient settings. Data on systemic biomarkers from large cohorts, including the well-characterized population of the ECLIPSE study, are now available and provide exciting information on the association of biomarkers with clinically important outcomes, including exacerbations, hospitalizations and mortality. Moreover, recent research has provided proof for the existence of distinct "systemic inflammatory" phenotypes. This review summarizes the currently available evidence on systemic biomarkers in COPD, providing clinically relevant information on the possible role of systemic biomarkers in the evaluation of disease activity and severity, phenotypes, outcomes, COPD exacerbations and treatment response and guidance. Despite the fact that no single biomarker is currently ready to characterize sufficiently the status of COPD patients, guide treatment options, and predict future events, recent studies have rendered our current knowledge definitely more advanced than a few years ago and the possible use of biomarkers in the diagnosis and management of COPD patients looks even more promising.

P213 The Prevalence and Impact of Gastro-Oesophageal Reflux Symptoms in Stable COPD Patients

IntroductionGastro-oesophageal reflux disease (GORD) has been associated with increased COPD exacerbation frequency (Terada et al, Thorax 2008) and was independently associated with the frequent exacerbator phenotype in the ECLIPSE study...

P214 Gastro-Oesophageal Reflux Symptoms During COPD Exacerbations

IntroductionGastro-oesophageal reflux disease (GORD) has been associated with increased COPD exacerbation frequency (Terada et al, Thorax 2008) and was independently associated with the frequent exacerbator phenotype in the ECLIPSE study...

Desmosine, a biomarker for COPD: old and in the way

In the assessment of clinical presentation and response to therapy in chronic obstructive pulmonary disease (COPD), there is a major need for the identification of suitable and reproducible parameters to evaluate disease progression and changes during interventional trials [1]; in other words, parameters (or markers) associated with clinical outcome. To date, this need has been met by forced expiratory volume in 1 s (FEV1), a robust physiological marker that, although a comprehensive and predictive tool, has numerous limitations [2]. The ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) exemplifies attempts made to find surrogate markers that are superior to FEV1 [3]. In ECLIPSE, subtypes from a large number of COPD patients and a variety of predictive/surrogate disease markers are being collected, including longitudinal data on lung physiology, imaging, health outcomes, genetics and biomarkers. Biomarkers have a special role in this setting. According to the US National Institutes of Health, a biomarker is defined as a “characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention” [4], and usually refers to a molecule or material, such as a cell or tissue [5]. As knowledge on the pathogenic processes of COPD broadens, an increasing number of putative biomarkers have been suggested and investigated, but enthusiasm over preliminary results is frequently followed by disappointment due to the lack of reproducibility and frustration due to the increasing number of biomarkers that have failed to live up to initial promises. Consequently, a useful biomarker for COPD is still lacking. …

Metabolic profiling detects biomarkers of protein degradation in COPD patients

There is a paucity of biomarkers for chronic obstructive pulmonary disease (COPD). Metabolomics were applied to a defined COPD patient cohort from the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points). Results were correlated with accepted biomarkers for the disease. Baseline control serum (n=66) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II (n=70), III (n=64) and IV (n=44) COPD patients were analysed by proton nuclear magnetic resonance ((1)H NMR). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to confirm amino acid changes detected by (1)H NMR. Data were correlated with body composition, emphysema and systemic inflammation. (1)H NMR identified decreased lipoproteins, N,N-dimethylglycine, and increased glutamine, phenylalanine, 3-methylhistidine and ketone bodies in COPD patients with decreased branched-chain amino acids (BCAAs) observed in GOLD stage IV patients. BCAAs, their degradation products, 3-methylhistidine, ketone bodies, and triglycerides were correlated negatively with cachexia and positively with systemic inflammation. Emphysema patients also displayed decreased serum creatine, glycine and N,N-dimethylglycine. LC-MS/MS confirmed (1)H NMR findings relating to BCAAs, glutamine and 3-methylhistidine in GOLD stage IV patients. NMR-based metabolomics characterised COPD patients based on systemic effects and lung function parameters. Increased protein turnover occurred in all COPD patients with increased protein degradation in individuals with emphysema and cachexia.

Genetics of Sputum Gene Expression in Chronic Obstructive Pulmonary Disease

Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus.

Novel Outcomes and End Points: Biomarkers in Chronic Obstructive Pulmonary Disease Clinical Trials

Biomarker development in chronic obstructive pulmonary disease (COPD) is a nascent field, in part because of the complexity underlying COPD pathogenesis. The objective of this review is to provide examples of how biomarkers may be effectively applied in clinical trials of COPD by limiting their use to specific contexts and using them to answer well delineated questions. Types of novel outcomes or "biomarkers" that may be useful in clinical trials in COPD include analyses performed on bronchoscopically obtained samples, sputum, exhaled gases, blood, and urine and "ex vivo" assays performed using biological samples obtained from trial participants. These novel biological outcomes are rarely useful as primary end points in phase III clinical trials in COPD, because they are not typically recognized by the U.S. Food and Drug Administration or other regulatory agencies. More commonly, the applications of these outcomes include "proof-of-concept" decisions, demonstration that the intervention had the intended pharmacologic or biological effect, identification of patient subgroups that benefit most, and safety monitoring. Examples given in this review include outcomes used in a phase IIA study of an inhaled small molecule inhibitor of epidermal growth factor receptor. Large observational studies of COPD, including the ECLIPSE, COPDGene, and SPIROMICS studies will further inform our use of biomarkers in COPD clinical trials. To encourage the application of novel biomarkers in clinical trials, the Food and Drug Administration has developed a new process for biomarker "qualification." This process has been designed to be more efficient and to promote consensus building and sharing of preclinical data.

Empirical comparison of three metrics suites for fault prediction in packages of object-oriented systems: A case study of Eclipse

► We empirically compared three suites of package-level metrics (Martin, MOOD and CK). ► We evaluated their accuracy in fault prediction in packages of Eclipse system. ► Seven prediction models were built using different combinations of the three suites. ► Prediction models that include subset of Martin metrics outperform the others. Packages are important high-level organizational units for large object-oriented systems. Package-level metrics characterize the attributes of packages such as size, complexity, and coupling. There is a need for empirical evidence to support the collection of these metrics and using them as early indicators of some important external software quality attributes. In this paper, three suites of package-level metrics (Martin, MOOD and CK) are evaluated and compared empirically in predicting the number of pre-release faults and the number of post-release faults in packages. Eclipse, one of the largest open source systems, is used as a case study. The results indicate that the prediction models that are based on Martin suite are more accurate than those that are based on MOOD and CK suites across releases of Eclipse.

Phenotypes of chronic obstructive pulmonary disease and the ECLIPSE study: preliminary results

Фенотипы больных хронической обструктивной болезнью легких и исследование ECLIPSE: первые результаты.

ECLIPSE: a French Study Concerning the Diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH)

AbstractAbstract 5134 Aim:PNH is a rare disease with prevalence between 7.3 and 15.9 cases/million. PNH is a life-threatening disease that affects mostly young adults with median age at diagnosis being 33 years. Diagnosis is difficult and often delayed because of the clinical polymorphism of the disease. ECLIPSE is a French study which aimed to evaluate the delay between the onset of PNH symptoms and the date of diagnosis, to identify the clinical signs leading to diagnosis and to determine which medical specialists are seen first by PNH patients (pts). Patients and Methods:4920 physicians were asked to participate in the study: 992 haematologists, 1638 internists, 1155 gastroenterologists, 697 nephrologists, 438 neurovascular physicians. Physicians were divided into 3 groups: (a) physicians having diagnosed PNH at least once, (b) having suspected a PNH without having confirmed the diagnosis, (c) neither having suspected nor diagnosed a PNH. The response rate was analysed by medical speciality and was defined by the number of physicians responding divided by the number of physicians invited to participate. Results:528 physicians accepted to participate in the study (overall response rate: 10.7%). In total, 507 answers were analysed. Among the 507 physicians, 108 (21 %) had diagnosed PNH at least once (group a), 213 (42 %) had suspected PNH without confirming the diagnosis (group b) and 186 (37 %, CI95% [32.49 % - 41.05 %]) neither had suspected nor diagnosed PNH (group c). In group (a), the clinical signs and symptoms which led to diagnosis were: pancytopenia 44%, anaemia 37%, haemolysis 23%, peripheral venous thrombosis 18%, hepatic vein thrombosis 14% and hemoglobinuria 14%. The physicians of group (a) were also asked to describe the clinical situations which raised the suspicion for PNH diagnosis: unexplained thrombosis (86%), hemoglobinuria (84%), aplastic anaemia (83%), Coombs negative anaemia (80%), cytopenias (71%) were the most frequent symptoms triggering the test for PNH. Physicians of group (a) were also asked to describe the circumstances of their latest PNH diagnosis. The patient was referred to the physician most frequently by the Emergencies (23%), a haematologist (22%) or by an internist (21%). The most frequent functional symptoms of their latest diagnosed pts were: fatigue (39%), anaemia (24%), abdominal pain (20%) and thrombosis (14%). Seven percent of PNH pts did not report any functional symptom before diagnosis. PNH diagnosis was confirmed in a mean time of 9.32±11.46 months after the onset of symptoms, and a maximum delay between first symptoms and diagnosis being 60 months. Biological signs which raised the suspicion for a PNH were: anaemia (80%), increase of LDH (60%), increase of biluribin (44%), thrombocytopenia (41%) and/or neutropenia (28%). Confirmation of PNH diagnosis was made by flow cytometry in 87% of the cases. Two hundred and thirteen physicians belong to group (b), having at least once suspected PNH without confirming diagnosis. Half of them (50%) had suspected at least 5 times a PNH diagnosis, without confirmation. Clinical and biological signs which prompted physicians of group (b) to suspect PNH were: Coombs negative anaemia (48%), pancytopenia (42%) and/or aplastic anaemia (38.5%), myelodysplastic syndrome (18%), hemoglobinuria (15.5%), increase level of LDH associated with venous or arterial thrombosis (15%), abdominal pain (14%), dark urine (12%) or jaundice (11%). Finally, 186 physicians declared having neither suspected nor diagnosed any PNH pts. Furthermore, 6.5% of physicians have never heard about PNH. Conclusions:PNH diagnosis is usually difficult and delayed as its signs and symptoms are diverse and non-specific. The ECLIPSE study aimed to better understand the diagnostic procedures for PNH, to evaluate the delay between onset of symptoms and diagnosis and to determine the medical specialists involved in the diagnosis and management of PNH pts. PNH is mainly diagnosed by hematologists. Frequent symptoms leading to diagnosis were unexplained thrombosis, hemoglobinuria, Coombs negative anaemia, but also aplastic anaemia, unexplained cytopenias and myelodysplastic syndrome. Flow cytometry, the gold standard for PNH testing, was only used in 87% of cases. Diagnosis was usually delayed with a maximum of 5 years between onset of PNH symptoms and diagnosis. Fatigue and abdominal pain were commonly reported symptoms and should therefore be more routinely assessed. Disclosures:No relevant conflicts of interest to declare.

Sputum neutrophils as a biomarker in COPD: findings from the ECLIPSE study

IntroductionThe percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation. We studied the relationships between sputum neutrophils and FEV1, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.MethodsSputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits. Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays. Low-dose CT scans evaluated emphysema.ResultsSputum neutrophil % increased with GOLD stage. There was a weak association between % sputum neutrophils and FEV1 % predicted (univariate r2 = 0.025 and 0.094 at baseline and year 1 respectively, p < 0.05 after multivariate regression). Similar weak but significant associations were observed between neutrophil % and health status measured using the St Georges Respiratory Questionairre. There were no associations between neutrophils and exacerbation rates or emphysema. Associations between sputum neutrophils and systemic biomarkers were non-significant or similarly weak. The mean change over 1 year in neutrophil % was an increase of 3.5%.ConclusionsSputum neutrophil measurements in COPD are associated weakly with FEV1 % predicted and health status. Sputum neutrophil measurements were dissociated from exacerbation rates, emphysema and systemic inflammation.

SPECTRAL MAPPING OF THE INTERMEDIATE POLAR DQ HERCULIS

We report an eclipse mapping study of the intermediate polar DQ Her based on time-resolved optical spectroscopy (~3800-5000A) covering 4 eclipses. Eclipse maps of the HeII 4686 line indicate that an azimuthally-and vertically-extended bright spot at disk rim is important source of reprocessing of x-rays from the magnetic poles. The disk spectrum is flat with no Balmer or Helium lines in the inner regions, and shows double-peaked emission lines in the intermediate and outer disk regions while the slope of the continuum becomes progressively redder with increasing radius. The inferred disk temperatures are in the range T~13500-5000K and can be reasonably well described by a steady-state disk with mass accretion rate of dM/dt=(2.7+/-1.0)x10^-9 Msun/yr. A comparison of the radial intensity distribution for the Balmer lines reveals a linear correlation between the slope of the distribution and the transition energy. The spectrum of the uneclipsed light is dominated by Balmer and HeI lines in emission with narrow absorption cores. The observed narrow and redshifted CaII 3934 absorption line in the total light spectra plus the inverse P-Cygni profiles of the Balmer and HeII 4686 emission lines in spectra of the asymmetric component indicate radial inflow of gas in the innermost disk regions and are best explained in terms of magnetically-controlled accretion inside the white dwarf magnetosphere. We infer projected radial inflow velocities of ~200-500km/s, significantly lower than both the rotational and the free-fall velocities for the corresponding range of radii. A combined net emission HeII plus Hbeta low-velocity eclipse map reveals a twisted dipole emitting pattern near disk center. This is interpreted as being the projection of accretion curtains onto the orbital plane at two specific spin phases, as a consequence of the selection in velocity provided by the spectral eclipse mapping.

Legal Bargaining Theory's New 'Prospecting' Agenda: It May Be Social Science, But is it News?

In the good old days legal bargaining scholarship was based mostly on negotiator war stories exuberantly told. The social-scientific study of the subject did not begin in earnest until the nineteen-seventies. Since then, however, the literature of storytelling has gone into a pronounced eclipse and social-scientific study is now the principal scholarly game in town. This article questions the wisdom of this shift, almost seismic in its proportions, and argues that it is too soon to jump on the social science bandwagon. Discussion focuses on the uses made of the Prospect Theory of Daniel Kahneman and Amos Tversky and the Theory's central concept of Anchoring. Anchoring is the most thoroughly analyzed of the Prospect Theory concepts and difficulties encountered in incorporating it into legal bargaining theory will recur many times over in working with other parts of the Prospect Theory framework. It is an exemplary test case.

Efficacy and Tolerability of Rosuvastatin and Atorvastatin when Force-Titrated in Patients with Primary Hypercholesterolemia

Background: Patients at high risk of cardiovascular disease frequently fail to reach recommended low-density lipoprotein cholesterol (LDL-C) goals, partly because statin doses are not titrated to optimal effect. The ECLIPSE study was designed to compare the efficacy and safety of force-titrated treatment with rosuvastatin (10–40 mg) with that of atorvastatin (10–80 mg) in high-risk patients with hypercholesterolemia. Methods: In this 24-week, open-label, randomized, multinational, parallel-group study, 1,036 patients were randomized to rosuvastatin (n = 522) or atorvastatin (n = 514). Results: At all time points, a significantly greater percentage of patients on rosuvastatin treatment achieved the NCEP ATP III LDL-C goal of <100 mg/dl (2.5 mmol/l), the 2003 European LDL-C target of <2.5 or 3.0 mmol/l (100 or 115 mg/dl) and the LDL-C goal of <70 mg/dl (1.8 mmol/l), a goal suggested for very high-risk patients (p < 0.001 for all). Rosuvastatin also achieved significantly greater improvements in components of the atherogenic lipid profile versus atorvastatin. Both treatments were well tolerated. Conclusion: Rosuvastatin titrated across its recommended dose range provides a more favorable effect on lipoprotein variables than atorvastatin, enabling more high-risk patients to achieve recommended LDL-C goals.