Lipid-modifying Therapy Research Articles

Atherosclerosis in type 2 diabetes: a role for fibrate therapy?

Vascular complications associated with type 2 diabetes confer significant morbidity and mortality. Atherosclerosis develops much earlier and progresses more rapidly than in subjects without diabetes. The clustering of cardiovascular risk factors associated with type 2 diabetes is mainly responsible for accelerated atherosclerotic disease. While statins remain the primary lipid-modifying therapy, the pharmacological profile of the fibrates suggests potential as an alternative or additional treatment for reducing the risk of atherosclerotic vascular complications in type 2 diabetes.

The Association of Lipid-Modifying Medications With Mortality in Patients on Long-Term Peritoneal Dialysis

The effect of lipid-lowering therapy on clinical outcomes in peritoneal dialysis patients has not been carefully addressed. Secondary analysis of a retrospective cohort study. Data from 1,053 incident peritoneal dialysis patients from the US Renal Data System prospective Dialysis Morbidity and Mortality Wave 2 study. Use of lipid-modifying medications (93% statins, 7% other medications). Cox regression with propensity score adjustment was used to evaluate time to cardiovascular or all-cause mortality during a 2-year follow-up period. Subgroups based on predefined cutoff values for serum total cholesterol or triglycerides, presence of diabetes, and comorbidity index were analyzed separately. Use of lipid-modifying medications was associated with decreased all-cause (hazard ratio [HR], 0.74; 95% confidence interval, 0.56 to 0.98) and cardiovascular (HR, 0.67; 95% confidence interval, 0.47 to 0.95) mortality compared with no use of lipid-modifying medications. In subgroup analyses, use of lipid-modifying medications was associated with decreased all-cause mortality (HR, 0.46; 95% confidence interval, 0.22 to 0.95) in the subgroups with cholesterol levels of 226 to 275 mg/dL (HR, 0.27; 95% confidence interval, 0.09 to 0.80) and cholesterol levels greater than 275 mg/dL and cardiovascular mortality (HR, 0.31; 95% confidence interval, 0.11 to 0.85) in the subgroup with cholesterol levels of 226 to 275 mg/dL. Use of lipid-modifying medications also was associated with decreased cardiovascular mortality (HR, 0.64; 95% confidence interval, 0.41 to 0.99) in patients with diabetes and decreased all-cause (HR, 0.65; 95% confidence interval, 0.45 to 0.94) and cardiovascular mortality (HR, 0.55; 95% confidence interval, 0.35 to 0.87) in those with Charlson Comorbidity Index score higher than 2. Observational study with retrospective design. Considerable amount of missing data and limited amount of information for the extreme values of cholesterol and triglycerides. These observational data suggest that lipid-modifying medication therapy may be associated with improved clinical outcomes in peritoneal dialysis patients.

LDL-C goal attainment among patients newly diagnosed with coronary heart disease or diabetes in a commercial HMO.

Patients beginning treatment with lipid-modifying drugs should have their serum lipid levels monitored and, if necessary, their drug therapy adjusted to reach and maintain their treatment goals. Patients with coronary heart disease or diabetes are at high risk of coronary events and are particularly important target groups for monitoring and dose adjustment of lipid-modifying drug therapy. to determine from administrative claims the rates of lipid testing, treatment with low-density lipoprotein cholesterol (LDL-C)-lowering drug therapy, and LDL-C goal attainment defined as LDL-C < 100 mg per DL in the time period after a new diagnosis of coronary heart disease or diabetes among patients who had not previously received lipid-modifying drug therapy. an index date was defined by a new diagnosis of coronary heart disease or diabetes between January 1, 1999 and December 31, 2000, preceded by a 12-month pre-index period without lipid-modifying drug treatment in a commercial health maintenance organization (HMO) database for the southeastern united states. coronary heart disease (CHD) was defined by a diagnosis code for myocardial infarction (International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] code 410.xx) or angina/ischemic heart disease (411.xx), or a procedural code for angioplasty (icd-9-cM 36.1x-36.3x; Current Procedural Terminology [CPT] 92980-92984, 92995-92996) or coronary artery bypass graft (icd-9-cM 36.01, 36.02, 36.05, 36.09; CPT 33510-33545). diabetes was identified either by an icd-9-cM diagnosis code 250.xx or a pharmacy claim for an antihyperglycemic medication. Patients were followed in the post-index period until loss of eligibility or a maximum of 42 months (mean = 26 months, range=12-42 months). We calculated the proportion of patients with lipids treated and at LDL-C goal (defined as V < 100 mg per DL) in months 1-6 after the index date. among those not at goal in months 1-6, we estimated the proportion treated to goal in months 7-12 and in month 7 to the end of the post-index period. Logistic regression was used to estimate the odds of goal attainment in months 7-12 and in month 7 to the end of the post-index period among patients who were not at goal in months 1-6. Laboratory lipid values were available for 4,676 (40.4%) of 11,552 patients who had not previously received lipid-modifying drug therapy in months 1-6 after the index date, of whom 72.7% (n = 3,400) had an LDL-C > or =100 mg per DL (63.5% for CHD and 76.7% for diabetes). Of 1,245 patients tested and treated with lipid-modifying therapy in months 1-6, 485 (39.0%) were at LDL-C goal in months 1-6 (48.2% of CHD and 28.8% of diabetes patients), and 760 (61.0%) were not at LDL-C goal (51.8% of those with CHD and 71.2% of those with diabetes). Goal attainment (cumulative) among those treated improved to 50.1% in months 7-12 and 58.4% in month 7 to the end of the post-index period. Patients not attaining goal in months 1-6, and who continued treatment in months 7-12 and month 13 to the end of the post-index period, had a 48.8% (95% confidence interval [CI], 44.0%-53.6%) predicted probability of attaining their goals. The odds of goal attainment in month 7 to the end of post-index period (among those not at goal in months 1-6) were greater for (a) age e 65 years (odds ratio [or] = 2.45, 95% CI, 1.62-3.72), (b) history of hypertension (or = 1.91, 95% CI, 1.20-3.03), (c) greater number of distinct medications (or = 1.07, 95% CI, 1.01-1.14 per additional medication), (d) months of observation post-index (or = 1.04, 95% CI = 1.01-1.08 per additional month), and (e) months supply of lipid-modifying medication (or = 1.04, 95% CI, 1.01-1.07 per additional month), and were lower for LDL-C > or = 130 mg per DL in months 1-6 (or = 0.53, 95% CI, 0.35-0.82) and a history of dyslipidemia (or = 0.54, 95% CI, 0.35-0.83). The odds of LDL-C goal attainment were not affected by diagnosis (CHD vs. diabetes), gender, statin titration (34% of patients), lipid-modifying drug switching (39% of patients), or treatment with a high-potency LDL-C-lowering drug dosage (one of sufficient strength to reduce LDL-C by > 40%). of patients receiving lipid testing and lipid drug treatment in the 6 months after an initial diagnosis of CHD or diabetes, 61% were not at the LDL-C goal of < 100 mg per DL. Among those not at LDL-C goal in the first 6 months of treatment, only about half who continued treatment subsequently attained their LDL-C goal, despite statin titration or switching of their lipid-modifying drug therapy.

Optimal medical therapy at discharge in patients with acute coronary syndromes: Temporal changes, characteristics, and 1-year outcome

There are limited data on the recent trend in the use of optimal evidence-based medical therapies after acute coronary syndromes (ACSs). We sought to evaluate (1) the temporal changes in medical management of patients discharged after an ACS; (2) patient and practice characteristics associated with optimal medical therapy at discharge; and (3) the association between discharge medication use and 1-year outcome. The Canadian ACS I (September 1999-June 2001) and ACS II (October 2002-December 2003) Registries were prospective, multicenter, observational studies of 6853 patients admitted for ACS. We examined the discharge use of medications among 5833 hospital survivors who did not have any contraindications to antiplatelet/anticoagulant, beta-blocker, angiotensin-converting enzyme inhibitor, or lipid-modifying therapies. Optimal medical therapy was defined as the use of all indicated medications. Follow-up data at 1 year were collected by telephone interview. We performed hierarchical logistic regression to identify patient characteristics and care patterns associated with optimal medical treatment and to examine its relationship with 1-year mortality. There were significant increases in the discharge use of all 4 classes of medications over time; 28.9% and 51.8% of patients in ACS I and ACS II Registries, respectively, were prescribed optimal medical therapy (P < .001). Advanced age, female sex, prior heart failure, renal dysfunction, and coronary bypass surgery during hospitalization were negative independent predictors of optimal medical therapy. Conversely, enrollment in ACS II Registry, history of dyslipidemia, presence of ST elevation and abnormal cardiac biomarker, previous myocardial infarction, and previous coronary revascularization were independently associated with the use of combination therapy. After adjusting for other validated prognosticators, patients receiving optimal medical therapy had significantly lower 1-year mortality (adjusted odds ratio 0.54, 95% confidence interval 0.36-0.81, P = .003) compared with those given 0 or 1 drug at discharge. Over the 1-year follow-up period, substantial numbers of patients discontinued therapies, whereas others were initiated on treatment. Despite the temporal increases in the combined use of evidence-based pharmacologic therapies, which is associated with improved outcome, medical management of ACS remains suboptimal. Quality improvement strategies are needed to enhance the appropriate use of effective therapies, targeting specifically the high-risk but undertreated patients who may derive the greatest therapeutic benefit.

Diabetic retinopathy: treatment and prevention

Diabetic eye disease is the major cause of blindness and vision loss among working-age people in developed countries. Microangiopathy and capillary occlusion underlie the pathogenesis of disease. While laser treatment is regarded as the standard therapy, intensive medical management of glycaemia and hypertension is also a priority in order to reduce the risk of diabetic retinopathy. Recent data have prompted a re-evaluation of the role of lipid-modifying therapy in reducing diabetic retinopathy. The Fenofibrate Intervention for Event Lowering in Diabetes (FIELD) study demonstrated a significant 30% relative reduction in the need for first retinal laser therapy in patients with (predominantly early-stage) type 2 diabetes treated with fenofibrate 200 mg daily, from 5.2% with placebo to 3.6% with fenofibrate, p=0.0003. The benefit of fenofibrate was evident within the first year of treatment. These promising data justify further evaluation of the mechanism and role of fenofibrate, in addition to standard therapy, in the management of diabetic retinopathy.

Testing the hypothesis of atherosclerotic plaque lipid depletion during lipid therapy by magnetic resonance imaging: Study design of Carotid Plaque Composition Study

In vivo testing of the lipid depletion hypothesis in human beings during lipid-modifying therapy has not been possible until recent developments in magnetic resonance imaging (MRI). The Carotid Plaque Composition Study is a prospective, randomized study designed to test the lipid depletion hypothesis in vivo. One hundred twenty-three subjects with coronary artery disease (CAD) or carotid disease and with levels of apolipoprotein B > or = 120 mg/dL (low-density lipoprotein levels 100-190 mg/dL) were enrolled and randomized to (1) single therapy--atorvastatin alone, placebos for extended release (ER)-niacin and colesevelam; (2) double therapy--atorvastatin plus ER-niacin (2 g/d), and placebo for colesevelam; (3) triple therapy--atorvastatin, ER-niacin, plus colesevelam (3.8 g/d). All subjects will undergo MRI scans of bilateral carotid arteries at baseline and annually for 3 years for a total of 4 examinations while on active therapy. Among these 123 subjects with mean age of 55 years and mean body mass index of 30 kg/m2, 73% are male, 43% have a family history of premature cardiovascular disease, 37% have had a previous myocardial infarction, 80% have clinically established CAD, 52% are hypertensive, 12% have diabetes, 23% are current smokers, and 47% meet the criteria for metabolic syndrome. The baseline carotid disease is evaluated using a MRI-modified American Heart Association lesion type definition. Of the 123 enrolled subjects, 40% have type III lesions with small eccentric plaque, 52% have type IV to V lesions with a necrotic core, and only 4% have calcified plaque based on the most diseased carotid location. The Carotid Plaque Composition Study uses a state-of-the-art imaging technology and comprehensive lipid management to test the plaque lipid depletion hypothesis in CAD subjects.

Metabolic Syndrome and Cardiovascular Disease: Challenges and Opportunities

Metabolic syndrome (MetS) has been defined in different ways. However, key components common to most definitions are a constellation of risk factors including abdominal adiposity, impaired fasting glucose, hypertension, and dyslipidemia. A major mediator of MetS appears to be insulin resistance, which relates to the development of the vascular and metabolic dysfunctions that precede overt cardiovascular disease and type 2 diabetes. Evidence suggests that the mechanisms underlying the elevated cardiovascular risk associated with MetS begin with subclinical organ damage. Therapy for MetS targets individual components of the syndrome and includes lifestyle interventions, lipid-modifying therapy, and antihypertensive agents, particularly those that inhibit the renin-angiotensin system. Results of trials of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have demonstrated reductions in new-onset diabetes and cardiovascular events in a wide range of patients. Clinical trials to investigate further the role of these drugs in the primary prevention of type 2 diabetes in patients with MetS are currently under way. The purpose of this paper is to review the MetS from the perspective of the cardiology workforce with the hope that a better understanding of the links between MetS and cardiovascular disease could lead to improved management of persons at risk.

A Randomized Trial of the Effect of Statin and Fibrate Therapy on Arterial Function in CKD

Although patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease (CVD), the roles of lipid-modifying therapies in decreasing CVD risk are unclear. Our aim is to compare the effects of statin and fibrate therapy on arterial function as a risk marker of CVD. Double-blind, randomized, placebo-controlled, parallel-group study. Ambulatory patients with stages 3 to 5 CKD. 6 weeks of atorvastatin, 40 mg/d, or gemfibrozil, 600 mg twice daily, with placebo. Primary outcome was arterial function assessed by means of endothelial-dependent flow-mediated dilatation (FMD) and small-artery compliance (C2). Secondary outcomes included endothelial-independent glyceryl trinitrate-mediated dilatation (GTNMD), large-artery compliance (C1), and levels of lipids, lipoproteins, and oxidized low-density lipoprotein, as well as markers of insulin resistance and inflammation. Compared with placebo, atorvastatin significantly decreased low-density lipoprotein (-52%), triglyceride (-30%), and oxidized low-density lipoprotein levels (-41%; P < 0.0001). Gemfibrozil significantly decreased triglyceride levels (-40%) and increased high-density lipoprotein levels (+20%; P < 0.0001). Neither atorvastatin nor gemfibrozil had a significant effect on markers of insulin resistance or inflammation. There was no significant change in FMD, GTNMD, or C1 with either atorvastatin or gemfibrozil. There was improvement in C2 with atorvastatin (+1.1 mL/mm Hg x 100) compared with placebo (P = 0.024), but not with gemfibrozil compared with placebo. Small sample size leading to inadequate power, short duration of therapy, and use of a heterogeneous group of patients with CKD and dialysis patients. In patients with advanced CKD, atorvastatin is associated with improvement in dyslipidemia and small-artery stiffness, but not endothelial function. Gemfibrozil improves dyslipidemia, but has no effect on arterial function.

Rosuvastatin: The Most Efficient Treatment Option For Patients With Dyslipidemia

It has been unequivocally proven that lowering serum cholesterol reduces the risk of cardiovascular disease. For every 1% reduction in serum total cholesterol, the risk of coronary heart disease is lowered by 2%, and with a 1 mmol/l reduction in low-density lipoprotein cholesterol (LDL-C), the 5-year incidence of major coronary events, coronary revascularization and stroke, is reduced by approximately one fifth. The risk of cardiovascular disease increases linearly with increasing serum cholesterol. Thus, people with high cholesterol levels have the highest risk, but in any population the largest number of cardiovascular events and deaths will occur in people whose serum cholesterol is only marginally elevated, as they form the largest pool of the background population. Unfortunately, a significant number of patients requiring lipid-modifying therapy remain untreated or suboptimally treated, with almost half failing to reach current guideline targets for LDL-C, and therefore remaining at unacceptably high risk of a cardiovascular event, such as a myocardial infarction or stroke, despite receiving medical treatment. This is partly due to noncompliance or ineffective use of cholesterol-lowering therapy. Consequently, there remains a need for an effective, well-tolerated agent or combination of such agents that can produce beneficial changes in the atherogenic lipid profile and enable the majority of patients requiring lipid-lowering therapy to reach their recommended LDL-C goals. Among the statins, rosuvastatin monotherapy has been shown to have superior efficacy in reducing LDL-C across its licensed dose range. At daily doses of 5–40 mg, rosuvastatin produces mean reductions in plasma LDL-C of 45–63%, achieves LDL-C goals in 48–89% of patients, and is more effective than equivalent and maximum doses of atorvastatin, simvastatin and pravastatin. This means that fewer patients treated with rosuvastatin will require other cholesterol-lowering agents, leading to lower treatment cost. Rosuvastatin also improves high-density lipoprotein cholesterol (HDL-C), triglyceride and lipid ratios, such as LDL-C:HDL-C ratio. Furthermore, a recent study showed that significant regression of atherosclerosis can be achieved with intensive statin therapy using rosuvastatin 40 mg. The safety and tolerability of rosuvastatin is similar to other marketed statins. Rosuvastatin as a single therapy is a valuable option and, thus far, the most efficient treatment for a broad spectrum of patients with dyslipidemia. In particular, the overall lipid profile, including HDL-C and triglycerides, in patients with Type 2 diabetes or the metabolic syndrome is markedly improved with rosuvastatin therapy.

Lipid-Modifying Therapy and Attainment of Cholesterol Goals in Hungary

Cardiovascular disease is a leading cause of death in Eastern Europe. Few studies on cholesterol goal achievement have been conducted in Hungarian clinical settings. This study set out to evaluate lipid-modifying therapy practices and their effects on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) goal attainment in Hungarian patients with coronary heart disease (CHD), CHD risk equivalents, or >or=2 coronary risk factors. This multicentre observational study involved patients receiving lipid-modifying therapy who were under the care of general practitioners (n = 300) or specialists (n = 140). Physician questionnaires were used to collect data on baseline patient characteristics, including laboratory parameters. Using validated cardiovascular risk assessment measures, patients were stratified into high-risk (10-year absolute coronary risk >20%; n = 367) and lower risk groups (n = 73). Cholesterol goals were TC <4.5 mmol/L (<175 mg/dL) and LDL-C <2.5 mmol/L (<100 mg/dL) for the high-risk group and TC <5.0 mmol/L (<193 mg/dL) and LDL-C <3.0 mmol/L (<117 mg/dL) for those at lower risk. Among 440 patients (n = 312 with CHD or CHD risk equivalents), 374 (85%) were initiated on HMG-CoA reductase inhibitors (statin monotherapy), 44 (10%) received fibric acid derivatives and 22 (5%) received combination regimens. Although >50% of patients needed >35% TC lowering to reach goal, <10% of patients received high or very high potency lipid-modifying regimens or combination regimens initially. A total of 116 (26.4%) patients achieved their TC goals after >/=1 year of treatment, including 27.9% of patients with CHD/risk equivalents and 22.7% of those with risk factors only. Sixty-six (15%) patients achieved goal on initial lipid-modifying regimens, while a further 50 (11.4%) achieved goal following treatment changes, including upward dosage adjustments. Approximately 74% of Hungarian patients receiving lipid-modifying therapy in our study did not achieve cholesterol goals. The proportion of patients realising their TC goals was higher in those treated by specialists but still did not exceed one-third.

Ezetimibe and fenofibrate combination therapy for mixed hyperlipidemia

The ezetimibe and fenofibrate combination regimen was recently approved by the U.S. Food and Drug Administration for treatment of mixed hyperlipidemia. This powerful lipid-modifying therapy takes advantage of the different mechanisms of action of the two individual components. Ezetimibe selectively inhibits intestinal uptake of dietary and biliary cholesterol, and exerts its effect most notably on the low-density lipoprotein cholesterol (LDL-C). Fenofibrate activates the peroxisome proliferators-activated receptor alpha (PPAR-alpha), thereby increasing the tissue lipoprotein lipase activity and breakdown of triglycerides in very low-density lipoproteins (VLDL). The combination therapy of ezetimibe and fenofibrate has an excellent safety profile and exhibits potent synergistic actions on multiple lipid risk factors and represents another alternative in the clinical management of mixed hyperlipidemia. Further studies are needed to determine the effectiveness and safety of the ezetimibe and fenofibrate combination therapy used in conjunction with other lipid-modifying agents such as statins. Finally, outcome trials are warranted to evaluate if combination therapy would result in additive effects on morbidity and mortality.

Efficacy and Safety of Torcetrapib, a Novel Cholesteryl Ester Transfer Protein Inhibitor, in Individuals With Below-Average High-Density Lipoprotein Cholesterol Levels

This study was designed to evaluate the efficacy and safety of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, in subjects with low high-density lipoprotein cholesterol (HDL-C) levels. Evidence suggests HDL-C is atheroprotective. A proven mechanism for increasing the level of HDL-C is the inhibition of CETP. A total of 162 subjects with below-average HDL-C (men <44 mg/dl; women <54 mg/dl) who were not taking lipid-modifying therapy were randomized to double-blind treatment with torcetrapib 10, 30, 60, or 90 mg/day or placebo ( approximately 30 subjects per group). The percent change from baseline to Week 8 with torcetrapib (least-squares mean difference from placebo) was dose-dependent and ranged from 9.0% to 54.5% for HDL-C (p < or = 0.0001 for 30 mg and higher doses) and from 3.0% to -16.5% for low-density lipoprotein cholesterol (LDL-C) (p < 0.01 for 90-mg dose). Low-density lipoprotein cholesterol lowering was less in subjects with higher (>150 mg/dl) versus lower levels of baseline triglycerides; at 60 mg, the change in LDL-C was 0.1% versus -22.2% (p < 0.0001), respectively. Particle size for both HDL and LDL increased with torcetrapib. There were no dose-related increases in the frequency of adverse events. Significant blood pressure increases were noted in 2 of 140 subjects. Torcetrapib resulted in substantial dose-dependent elevations in HDL-C, accompanied by moderate decreases in LDL-C at the higher doses. Torcetrapib was generally well tolerated.

Reducing vascular risk in the diabetic patient: implications from the FIELD study

The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, involving 9, 795 patients with type 2 diabetes, is the largest study to date investigating the role of a lipid-modifying therapy in reducing cardiovascular risk in type 2 diabetes. Although the reduction in the primary end point (non-fatal myocar-dial infarction [MI] and coronary heart disease [CHD] death) did not reach statistical significance, fenofibrate treatment was associated with a significant reduction in total cardiovascular events, largely driven by reductions in non-fatal MI and revascularisation procedures. Subgroup analyses demonstrated greater treatment effect in patients without prior cardiovascular disease than in those with established cardiovascular disease (relative risk reduction for CHD events of 25%, p=0.014 vs. a non-significant 8% increase, respectively; and for total cardiovascular events of 19%, p=0.004 vs. no effect). Differences in the magnitude of the reduction in cardiovascular risk between studies emphasise the importance of considering patient characteristics, such as duration of diabetes, concomitant lipid-modifying therapy, glycaemic control and prior cardiovascular disease, which may all influence treatment response. Taking these factors into account, as well as the promising effects on microangiopathy observed in FIELD, suggests that fenofibrate may have a role as a well-tolerated treatment (most likely in combination with a statin) in patients with early stage type 2 diabetes without evidence of macrovascular disease.

Impact of rosuvastatin use on costs and outcomes in patients at high risk for cardiovascular disease in US managed care and medicare populations: A data analysis

Background: High blood cholesterol is a major modifiable risk factor for coronary heart disease (CHD) and stroke. Objective: The aim of this study was to estimate the economic impact of rosuvastatin calcium use in patients at high risk for CHD and stroke, according to the National Cholesterol Education Program Adult Treatment Panel (ATP) III guidelines. Methods: An economic simulation model was developed that used a Markov process to project the number of cardiovascular events and associated costs in a high-risk population in various treatment scenarios. According to the ATP III, high-risk patients are those with CHD, atherosclerosis of peripheral and/or cerebral arteries, diabetes, and/or multiple other risk factors conferring a risk of at least 20% within 10 years. Data on population characteristics and costs of cardiovascular disease (CVD) were obtained from claims data sets from employer-funded commercial and Medicare health plans in the United States. Treatment of lipid disorders was translated into CVD risk reduction based on results from the Heart Protection Study. The estimated efficacies of individual lipid-lowering drugs were based on data published in package inserts. The model generated costs at the health plan level of lipid-lowering therapy in high-risk patients and the number and total costs of cardiovascular events. Estimates were compared for scenarios representing the mix of treatments used before and after the introduction of rosuvastatin. Estimates were generated separately for commercial and Medicare health plans. Results: For every 1 million members of a commercial health plan, an estimated 44,457 met ATP III criteria for high-risk status. Use of rosuvastatin in place of other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (“statins”) by 11 % of these patients over a period of 5 years was estimated to result in 36 fewer cardiovascular events and a net savings of US $4.03 million. A Medicare plan of 1 million members with an estimated 433,268 high-risk patients and 7% rosuvastatin use was estimated to avoid 727 events and save US $34.32 million. Conclusions: The results of this data analysis suggest that increasing the use of rosuvastatin can result in cardiovascular event reduction and cost savings. Because the impact of lipid-modifying therapy on cardiovascular risk has not been thoroughly documented in controlled clinical studies, our model assumed that incremental lipid changes had effects in proportion to the magnitude of change.

Dyslipidaemia in diabetic patients: time for a rethink

Patients with type 2 diabetes have a marked increase in the risk of premature coronary heart disease (CHD). One of the underlying reasons for this increased risk is atherogenic dyslipidaemia, which is common in this patient group and characterized by low plasma levels of high-density lipoprotein cholesterol (HDL-C), increased levels of serum triglycerides, specifically very low-density lipoprotein triglycerides, and an increase in small, dense low-density lipoprotein (LDL) particles. Current management strategies focus on the initial use of statin or fibrate therapy (the latter approach indicated in patients with pronounced hypertriglyceridaemia). Recent treatment guidelines also emphasize the need for reduction in LDL-cholesterol (LDL-C) below 100 mg/dl (2.6 mmol/l) in diabetic patients, as this patient group has a clustering of cardiovascular risk factors that collectively lead to an excess risk of premature mortality. Multidrug lipid-modifying therapy has been proposed to further reduce CHD risk in diabetic patients. Adding nicotinic acid to primary statin therapy would be a logical approach based on the complementary therapeutic benefits of these treatments. Nicotinic acid is the most potent agent currently available for raising HDL-C and is also effective in reducing triglycerides and LDL-C. Moreover, clinical trial data have shown that nicotinic acid can be safely used in diabetic patients. Data from the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER 2) study in patients with established CHD and low HDL-C (27% of whom had type 2 diabetes) show the atheroprotective effects of nicotinic acid/statin combination therapy. The clinical benefits of this combination therapy are indicated by subgroup analyses from the HDL-Atherosclerosis Treatment Study, which showed 40% reduction in coronary event frequency in patients with impaired glucose tolerance. Together, these data support the proposed strategy of aggressive multidrug treatment of diabetic dyslipidaemia to improve patient outcome.

Contemporary Management of Dyslipidemia in High-Risk Patients: Targets Still Not Met

Purpose Our objective was to evaluate treatment patterns and the attainment of current National Cholesterol Education Program (NCEP)-recommended lipid targets in unselected high-risk ambulatory patients. Methods Between December 2001 and December 2004, the prospective Vascular Protection and Guidelines Oriented Approach to Lipid Lowering Registries recruited 8056 outpatients with diabetes, established cardiovascular disease (CVD), or both, who had a complete lipid profile measured within 6 months before enrollment. The primary outcome measure was treatment success, defined as the achievement of LDL-cholesterol < 2.6 mmol/L (100 mg/dL) according to NCEP guidelines. We examined patient characteristics and use of lipid-modifying therapy in relation to treatment outcome, which included the recently proposed optional LDL-cholesterol target (<1.8 mmol/L [70mg/dL]) for very high-risk patients. Results Overall, 78.2% of patients were treated with a statin and 51.2% had achieved the recommended LDL-cholesterol target. Treatment success rate was highest in diabetic patients with CVD (59.6%), followed by nondiabetic patients with CVD (51.8%), and lowest (44.8%) in diabetic patients without CVD ( P < .0001). Compared with untreated patients, those on statins were more likely to achieve target (34.4% vs 55.9%, P < .0001). Of the patients who failed to meet target, only 9.9% were taking high-dose statin, while 29.3% were not prescribed any statin therapy. Among very high-risk patients, 20.8% attained the optional LDL-cholesterol goal. In multivariable analysis, advanced age, male sex, diabetes, coronary artery disease, coronary revascularization, and use of statin were associated with treatment success (all P < .0001). Conclusion Despite the well-established benefits of available lipid-modifying drugs, current management of dyslipidemia continues to be suboptimal, with a substantial proportion of patients failing to achieve guideline-recommended lipid targets. There remains an important opportunity to improve the quality of care for these high-risk patients.

Achieving 2003 European lipid goals with rosuvastatin and comparator statins in 6743 patients in real-life clinical practice: DISCOVERY meta-analysis

ABSTRACTBackground: There is an increasing body of evidence to support the benefits of reducing low-density lipoprotein cholesterol (LDL-C) levels and this has been reflected in a lowering of LDL-C goals recommended by international guidelines. Therefore, there is a growing need for effective lipid-modifying therapies to optimise the achievement of these more stringent LDL-C goals.Objective: A meta-analysis of data pooled from five studies participating in the DISCOVERY (DIrect Statin COmparison of LDL‐C Values: an Evaluation of Rosuvastatin therapY) Programme was performed to compare the effect of rosuvastatin treatment with other statins in real-life clinical practice.Results: These studies included 6743 patients with hypercholesterolaemia from different ethnicities, countries and cultural environments. The meta-analysis showed that significantly more patients receiving rosuvastatin 10 mg achieved the 2003 European LDL‐C goals compared with those who received atorvastatin 10 mg or simvastatin 20 mg ( p < 0.001 for both comparisons). A significantly greater proportion of patients receiving rosuvastatin 10 mg also achieved the 2003 European total cholesterol goal compared with those on atorvastatin 10 mg ( p < 0.001).Conclusions: The meta-analysis showed that rosuvastatin was more effective than comparator statins at lowering LDL‐C levels and enabling patients to achieve lipid goals at recommended start doses. In addition, all statins studied were well tolerated and confirmed that rosuvastatin had a similar safety profile to other statins.

Role of the Pharmacist in the Management of Dyslipidemia

Dyslipidemia is one of a number of independent risk factors for cardiovascular disease. Numerous large-scale, randomized clinical trials demonstrate the benefit of aggressive lipid-modifying therapy in reducing the mortality and morbidity associated with cardiovascular disease. Despite these data and the wide dissemination of clinical practice guidelines outlining management strategies for patients with dyslipidemia, particularly those at the greatest cardiovascular risk, studies indicate that a significant proportion of patients are not screened, initiated on appropriate therapy, or treated to target lipid levels. Pharmacists, as part of the multidisciplinary team, can play a vital role in assisting in the management of patients with dyslipidemias. This article reviews published studies that have evaluated the pharmacist's role in lipid management, reviews the process for managing a patient with dyslipidemia, and provides suggestions on how pharmacists can become more involved in lipid management.

Lipid Management and Cholesterol Goal Attainment in Norway

To document prescribing patterns of lipid-modifying therapies in hypercholesterolemic patients, cholesterol goal attainment, and factors associated with cholesterol goal attainment in Norway. This was a retrospective, observational study using existing computerized patient records at 11 primary healthcare centers in Norway and the Norwegian Patient Register of hospital data. The study population was 3111 patients identified in the primary care database who were prescribed a lipid-modifying therapy between the dates of July 1987 and May 2003 and who were > or = 18 years of age at the time of the first prescription. Of these patients, 1337 patients had uncontrolled lipid measures at baseline. In the analysis of goal attainment, data were available for 877 (28% of the total study population) and 1144 (37%) patients with baseline and follow-up total cholesterol (TC) and/or low-density lipoprotein-cholesterol (LDL-C) levels after 4 and 12 months' treatment, respectively. Initial lipid-modifying therapy (drug and dosage), changes in initial lipid-modifying therapy, cholesterol goal attainment, and factors related to cholesterol goal attainment. Cholesterol treatment goals were defined as LDL-C <3.0 mmol/L and/or TC <5.0 mmol/L (as per the Second Joint Task Force of European Societies on the Prevention of Cardiovascular Disease). The initial lipid-modifying therapy was a HMG-CoA reductase inhibitor (statin) in 98% of patients, most often simvastatin (42%; mean initial dosage = 18.4 mg/day) or atorvastatin (34%; 12.7 mg/day). The median year of treatment initiation was 1999 and the mean duration of follow-up was 39 months. The initial prescription remained unchanged at year 1 for most patients (69%), whereas 17% discontinued drug treatment. Mean TC levels decreased from 7.36 mmol/L at baseline (n = 1337) to 5.31 mmol/L at 12 months (n = 1144; p < 0.05), whereas mean LDL-C levels decreased from 4.98 (n = 847) to 3.08 mmol/L at 12 months (n = 713; p < 0.05). These mean reductions occurred within 3 months of the initial prescription and did not change subsequently. A total of 32.9% of patients who were not at goal at baseline achieved cholesterol goal 12 months after initiating treatment. The factors related to cholesterol goal attainment at 12 months were: baseline TC level (odds ratio [OR] 0.64; 95% CI 0.58, 0.71), treatment with a statin (OR 8.60; 95% CI 1.13, 65.4), diagnosis of diabetes mellitus (OR 2.91; 95% CI 2.01, 4.21), and age (OR 1.02; 95% CI 1.01, 1.03). Lipid-modifying therapy in Norway is dominated by statin monotherapy. In this analysis of primary-care patients, maximal reductions in cholesterol levels were seen within the first 3-4 months after therapy initiation. After 12 months of treatment, 67% of patients remained above recommended cholesterol levels. More effective and well tolerated treatment strategies are needed to improve the probability of patients achieving cholesterol treatment goals.

Non-invasive Atherosclerosis Imaging: Use to Assess Response to Novel or Combination Lipid Therapies

Despite significant protection from cardiovascular events by HMG-CoA reductase inhibitors (statins), the extent of event reduction is incomplete and persistent lipid abnormalities remain prevalent. As such, the use of combination lipid modification regimens is a clinical reality. While we await large, randomized clinical outcomes trials assessing the benefits of combination or novel lipid management therapies, non-invasive imaging tests such as B-mode ultrasound to measure carotid intima-media thickness (CIMT), coronary computed tomography (CT) and cardiovascular magnetic resonance imaging (CMR) are increasingly being utilized to accurately assess the impact of lipid modifying therapies on atherosclerosis. Based on knowledge that atherosclerosis progression is a validated surrogate for increased cardiovascular risk, use of atherosclerosis imaging surrogates in studies allows for smaller sample sizes, shortens study duration, demonstrates clinically meaningful changes prior to clinical event and provides potentially useful pathophysiologic information. CIMT measurement is currently the most studied and validated non-invasive imaging study used to assess atherosclerosis longitudinally in response to lipid modification therapies. Quantification of coronary calcium using coronary CT has been utilized to study atherosclerosis longitudinally, however, calcium scoring to assess response to lipid modifying therapies is not recommended due to several limitations of this assessment of the atherosclerosis process. These include the fact that non-calcified atherosclerosis is not quantified, that the calcification process in atherosclerosis is diverse and that the effects of statins on tissue calcification are complex. Use of contrast coronary CT to image non-calcified coronary atherosclerosis is promising. Modern CMR imaging, aided by high reproducibility and image resolution, is rapidly advancing and early studies imaging non-coronary and coronary atherosclerosis are impressive.