Treatment of high-risk older persons with lipid-lowering drug therapy

Randomized, double-blind, placebo-controlled studies and observational studies have demonstrated that statins reduce mortality and major cardiovascular events in high-risk persons with hypercholesterolemia. The aim of this study was to review the evidence for treating high-risk older persons with lipid-lowering drugs. A MEDLINE search of the English-language literature published from January 1, 1989, to June 2006 was conducted to review all studies in which lipid-lowering drug therapy was administered to high-risk older persons. The Heart Protection Study showed that statins reduced mortality and major cardiovascular events in high-risk persons, regardless of the initial level of serum lipids, age, or gender. The updated National Cholesterol Education Program (NCEP) III guidelines state that in very-high-risk patients, a serum low-density lipoprotein (LDL) cholesterol level of <70 mg/dL is a reasonable clinical strategy, regardless of age. When a high-risk person has hypertriglyceridemia or low serum high-density lipoprotein cholesterol, consideration can be given to combining a fibrate or nicotinic acid with an LDL cholesterol-lowering drug. For moderately-high-risk persons, the serum LDL cholesterol should be reduced to <100 mg/dL. When LDL cholesterol-lowering drug therapy is used for high-risk persons or moderately-high-risk persons, the serum LDL cholesterol should be reduced at least 30% to 40%. High-risk older persons should be treated with lipid-lowering drugs according to the NCEP III updated guidelines to reduce cardiovascular morbidity and mortality.     

Influence of atorvastatin versus simvastatin on fibrinogen and other hemorheological parameters in patients with severe hypercholesterolemia treated with regular low-density lipoprotein immunoadsorption apheresis.

Low-density lipoprotein (LDL) apheresis is a treatment option in patients with coronary artery disease and elevated LDL cholesterol concentrations if maximal drug therapy fails to achieve adequate LDL cholesterol reduction. This therapy is more effective when combined with strong lipid-lowering drugs, such as atorvastatin. However, conflicting data have been published concerning the effect of atorvastatin on fibrinogen concentration. Therefore, we investigated the effect of atorvastatin compared to simvastatin on fibrinogen concentration and other hemorheological parameters in patients treated by weekly LDL apheresis. Hemorheological parameters were, studied twice in 9 patients (4 female, 5 male, 54.0+/-8.9 years) with coronary artery disease treated by weekly LDL immunoadsorption, once during concomitant simvastatin therapy (40 mg daily) and once during atorvastatin therapy (40 mg daily). Fibrinogen concentration, plasma and blood viscosity at different shear rates, parameters of red cell aggregation at stasis and shear rate 3/s, and erythrocyte filterability were determined 7 days after the last LDL apheresis after each drug had been given for a minimum for 8 weeks. Fibrinogen concentration did not show any statistically significant difference during therapy with atorvastatin (3.09+/-0.36 g/L) compared to simvastatin (3.13+/-0.77 g/L). Plasma and blood viscosity as well as erythrocyte filterability were also unchanged. The increase in red cell aggregation at stasis during atorvastatin treatment (5.82+/-1.00 U versus 4.89+/-0.48 U during simvastatin; p < 0.05) was inversely correlated with a lower high-density liprotein (HDL) cholesterol concentration (1.17+/-0.21 mmol/L versus 1.31+/-0.30 mmol/L during simvastatin; p < 0.05). LDL cholesterol showed a strong trend to lower concentrations during atorvastatin (4.14+/-0.61 mmol/L versus 4.56+/-0.66 mmol/L during simvastatin; p = 0.07), despite a reduced plasma volume treated (3,547+/-1,239 ml during atorvastatin versus 3,888+/-1,206 mL during simvastatin; p < 0.05). In conclusion, fibrinogen concentration and other hemorheological parameters were unchanged during atorvastatin compared to simvastatin therapy with the exception of a higher red cell aggregation at stasis. Therefore, with respect to hemorheology, we conclude that atorvastatin should not be withheld from hypercholesterolemic patients regularly treated with LDL immunoadsorption.     

Lipid-lowering therapy in patients with peripheral arterial disease: are guidelines being met?

OBJECTIVES: To determine the proportion of patients with lower extremity peripheral arterial disease (PAD) who reach recommended low-density lipoprotein cholesterol (LDL-C) levels (<100 mg/dL) and to identify the patient characteristics that are independently associated with attaining the LDL-C goal (<100 mg/dL). PATIENTS AND METHODS: Eligible patients were identified from a roster of patients who had undergone testing at a nonvascular laboratory between September 1, 2001, and January 31, 2002, and were found to have evidence of PAD, defined as an ankle-brachial index of 0.9 or less. We thoroughly reviewed patients' electronic medical records. Backward elimination multivariate logistic regression modeling was used to Identify factors associated with reaching the goal LDL-C level. RESULTS: Among 143 patients with PAD, 105 (73%) met the goal LDL-C level. Lipid-lowering therapy was prescribed for 109 (76%). Lower diastolic blood pressure and lower weight were independently associated with an LDL-C level of less than 100 mg/dL. CONCLUSION: We found higher rates of lipid-lowering therapy in patients with PAD than reported previously. Patients with diabetes mellitus or coronary artery disease were not more likely to meet the goal LDL-C level than those without these comorbidities. Clinical practice may be catching up to clinical guidelines.     

The Lipoprotein and Coronary Atherosclerosis Study (LCAS): Design,methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia

Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease (CHD) and normal or only slightly elevated plasma cholesterol concentrations. The one published angiographic trial designed to examine this question found no benefit. Additional prospective data will be provided by the Lipoprotein and Coronary Atherosclerosis Study (LCAS), a randomized, double-blind, placebo-controlled trial of fluvastatin therapy (20 mg twice daily) monitored by both quantitative coronary angiography (QCA) and, in a subset of patients, positron-emission tomography (PET). Eligible subjects in LCAS were men and women 35–75 years of age with low-density lipoprotein (LDL) cholesterol of 115–190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30–75% diameter stenosis. Among the 429 patients randomized (mean age 58.8, 81% male), mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prerandomization LDL cholesterol of 160 mg/dL or higher also received open-label adjunctive cholestyramine. The primary endpoint is within-patient per-lesion change in minimum lumen diameter (MLD) as measured by QCA at baseline and 2.5-year follow-up. All evaluable lesions had MLD at least 0.8 mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25% of the reference lumen diameter at baseline. Data obtained on myocardial perfusion changes (99 patients underwent initial PET), special lipid particles, and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment.     

Achieving low-density lipoprotein cholesterol goals in high-risk patients in managed care: comparison of rosuvastatin, atorvastatin, and simvastatin in the SOLAR trial

OBJECTIVE: To evaluate attainment of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol (LDL-C) goal of less than 100 mg/dL with statin treatments in managed care patients at high risk for coronary heart disease. PATIENTS AND METHODS: In a randomized, open-label, multicenter trial (SOLAR [Satisfying Optimal LDL-C ATP III goals with Rosuvastatin]) performed at 145 US clinical centers from June 5, 2002 to July 12, 2004, high-risk men and women in a managed care population received typical starting doses of rosuvastatin (10 mg/d), atorvastatin (10 mg/d), or simvastatin (20 mg/d) for 6 weeks. Those who did not meet the LDL-C target of less than 100 mg/dL at 6 weeks had their dose titrated (doubled), and all patients were followed up for another 6 weeks. RESULTS: A total of 1632 patients were randomized to 1 of the 3 treatment regimens. After 6 weeks, 65% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 41% with atorvastatin and 39% with simvastatin (P<.001 vs rosuvastatin for both). After 12 weeks, 76% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 58% with atorvastatin and 53% with simvastatin (P<.001 vs rosuvastatin for both). Reductions in the LDL-C level, total cholesterol level, non-high-density lipoprotein cholesterol (non-HDL-C) level, and non-HDL-C/HDL-C ratio were significantly greater with rosuvastatin at both 6 and 12 weeks compared with the other statins. Adverse events were similar in type and frequency in all treatment groups, and only 3% of all patients discontinued treatment because of adverse events. No myopathy was observed, no clinically important impact on renal function was attributed to study medications, and clinically important increases in serum transaminases were rare. CONCLUSION: In a managed care population, 10 mg of rosuvastatin treatment resulted in more patients reaching the NCEP ATP III LDL-C goal compared with 10 mg of atorvastatin and 20 mg of simvastatin, potentially reducing the need for titration visits.     

Implication of the new low-density lipoprotein goals in dyslipidemia management of patients with acute coronary syndrome

OBJECTIVE: To assess the ability of patients with an acute coronary syndrome (ACS) to meet the recommended low-density lipoprotein cholesterol (LDL-C) goal of 100 mg/dL and optional aggressive lowering to 70 mg/dL. PATIENTS AND METHODS: Patients diagnosed as having ACS who had lipid levels measured within 24 hours of admission from January 1, 1998, through December 31, 2002, were assessed for the ability to meet the 2 target LDL-C levels. Patients were considered to have ACS if they were diagnosed as having myocardial infarction, had significant disease on angiography, or had a history of coronary artery disease. Patients were classified into 1 of 4 groups on the basis of the degree of LDL-C lowering required to meet the 2 different goals: less than 33%, 33% to 39%, 40% to 49%, and 50% or more. Patients with myocardial infarction who had lipid sampling performed more than 24 hours after admission were excluded. RESULTS: The mean plus-or-minus SD LDL-C level was 111 plus-or-minus 43 mg/dL in the 1322 patients who met criteria for ACS and had LDL-C levels assessed. On the basis of a target LDL-C value of less than 100 mg/dL, 43% of patients were at goal and did not require treatment, and only 2.5% had an LDL-C level that required a 50% or greater reduction to meet goal. In contrast, using the newer LDL-C target of 70 mg/dL, 85% patients required treatment, and 23% of patients required a 50% or greater decrease in LDL-C level and therefore were likely to require more than 1 lipid-lowering agent. CONCLUSION: Decreasing the LDL-C target to less than 70 mg/dL substantially increases the number of patients with ACS who would require treatment. A significant proportion of patients will require a reduction in LDL-C level of 50% or more, which is not easily achievable with current lipid-lowering monotherapy.     

Medical management of stable coronary artery disease

All patients with stable coronary artery disease require medical therapy to prevent disease progression and recurrent cardiovascular events. Three classes of medication are essential to therapy: lipid-lowering, antihypertensive, and antiplatelet agents. Lipid-lowering therapy is necessary to decrease low-density lipoprotein cholesterol to a target level of less than 100 mg per dL, and physicians should consider a goal of less than 70 mg per dL for very high-risk patients. Statins have demonstrated clear benefits in morbidity and mortality in the secondary prevention of coronary artery disease; other medications that can be used in addition to statins to lower cholesterol include ezetimibe, fibrates, and nicotinic acid. Blood pressure therapy for patients with coronary artery disease should start with beta blockers and angiotensin-converting enzyme inhibitors. If these medications are not tolerated, calcium channel blockers or angiotensin receptor blockers are acceptable alternatives. Aspirin is the first-line antiplatelet agent except in patients who have recently had a myocardial infarction or undergone stent placement, in which case clopidogrel is recommended. Anginal symptoms of coronary artery disease can be treated with beta blockers, calcium channel blockers, nitrates, or any combination of these. Familiarity with these medications and with the evidence supporting their use is essential to reducing morbidity and mortality in patients with coronary artery disease.     

Treating serum lipid abnormalities in high-priority patients

Normalization of serum lipid levels should be initiated as soon as possible in patients with myocardial, cerebrovascular, or peripheral vascular disease. Clinical trials indicate that coronary artery disease and overall mortality rates can be reduced and atherosclerosis stabilized or reversed by lipid-lowering therapy. Treatment should lower low-density lipoprotein cholesterol levels to 130 mg/dL or less and total triglyceride levels to 150 mg/dL or less and increase high-density lipoprotein cholesterol levels to at least 52 mg/dL in men and 66 mg/dL in women. Nonlipid coronary risk factors should be eliminated when possible. Lipid-lowering therapy may consist of dietary modification and drug treatment with colestipol hydrochloride (Colestid), cholestyramine (Cholybar, Questran), lovastatin (Mevacor), gemfibrozil (Lopid), and nicotinic acid (Nicolar).     

Meaning of low-density lipoprotein-apheresis for hypercholesterolemic patients at high risk for recurrence of coronary heart disease.

The goal of cholesterol-lowering therapy in hypercholesterolemic patients at high risk for recurrence of coronary heart disease (CHD) is the prevention of acute coronary syndrome by stabilization of coronary atheromatous plaque. We often encounter patients in whom it is difficult to maintain the serum cholesterol level at a desirable level with dietary therapy and drug treatment, despite the development and use of statins. For secondary prevention in patients who are at high risk for the recurrence of CHD and whose cholesterol level cannot be controlled by drugs alone, low-density lipoprotein (LDL)-apheresis therapy, which involves removal of LDL through extracorporeal circulation, is now available. Many reports concerning improvement of vascular endothelial function, improvement of myocardial ischemia, regression of coronary atherosclerotic lesions, stabilization of coronary plaque, and reduction in the incidence of cardiac events as a result of LDL-apheresis treatment have been published in various countries. We believe that LDL-apheresis should be performed on hypercholesterolemic patients with existing CHD for whom diet and maximum cholesterol-lowering drug therapies have been ineffective or not tolerated and whose LDL cholesterol level is 160 mg/dL or higher.     

Circulating electronegatively charged low-density lipoprotein in patients with angiographically documented coronary artery disease

There is growing experimental evidence to suggest the role of oxidatively modified low-density lipoprotein (LDL) in the initiation and progression of atherosclerosis. The oxidation of lipoprotein moiety causes modification of positively charged lysine residues and results in negative net charge of lipoprotein particles. OBJECTIVE: To measure the amount of circulating electronegatively charged LDL particles (LDL-) in plasma of patients with angiographically documented coronary artery disease (CAD). METHODS: Thirty patients were assigned to the study group (CAD+) and 10 patients to the control group (Ctrl). LDL- was quantitated in homogeneous LDL fractions obtained by ultracentrifugation, using ion exchange high performance liquid chromatography. Plasma lipids were measured using enzymatic kits. RESULTS: The CAD+ group had significantly higher levels of LDL- in the whole LDL fraction (7.66+/-1.92 vs. 5.14+/-0.84%, p=0.0003). Moreover the CAD+ group had significantly higher levels of total cholesterol (255.4+/-35.1 vs. 210.4+/-22.4 mg/dL), LDL cholesterol (154.5+/-26.9 vs. 122.4+/-21.1 mg/dL) and significantly lower levels of high-density lipoprotein (HDL) cholesterol (40.4+/-9.4 vs. 51.0+/-11.5 mg/dL). LDL- remained significantly higher in the CAD+ group after adjustment for total cholesterol, LDL cholesterol and HDL cholesterol (6.3 vs. 5.14% at p=0.0095). There is a trend towards a positive correlation between LDL- levels and LDL cholesterol in the control group (Spearman R=0.55 at p=0.098). CONCLUSIONS: Electronegatively charged LDL appears to be an additional hallmark of coronary artery disease, independently of established lipid risk factors. The trend towards a positive correlation between LDL cholesterol concentration and the level of LDL- in the control group may reflect the susceptibility of LDL cholesterol to autoxidation, Moreover, this may indicate other oxidative mechanisms in coronary artery disease. Nonetheless, further studies assessing the prognostic value of electronegatively charged LDLs are necessary.     

Low-density lipoprotein apheresis using the liposorber dextran sulfate cellulose system for patients with hypercholesterolemia refractory to medical therapy

A subset of patients with familial hypercholesterolemia (FH) have an inadequate lipid-lowering response to diet and drug treatment and should be considered for low-density lipoprotein (LDL)-apheresis therapy. This procedure selectively removes apolipoprotein B-containing particles [LDL, very-low-density lipoprotein, lipoprotein(a)] from plasma independent of diet and drug therapy. Methods for performing LDL-apheresis include dextran sulfate cellulose adsorption, immunoadsorption, and heparin-induced extracorporeal precipitation. The Liposorber Study Group evaluated LDL removal using the Liposorber® LA-15 LDL-apheresis System in 64 patients with FH who had not responded adequately to diet and maximal drug therapy. Mean acute reductions in LDL cholesterol (LDL-C) were 76% in heterozygous FH (HtFH) patients and 81% in homozygous FH (HoFH) patients. Time-averaged levels of LDL-C were lowered 41% in HtFH and 53% in HoFH patients. Hypotension was the most frequent side effect, occurring in 3% of procedures. The Liposorber® LA-15 System has been approved by the Food and Drug Administration and is recommended for 1) patients with functional homozygous FH (LDL-C level >500 mg/dL; 2) patients with coronary artery disease (CAD) and LDL-C levels ≥200 mg/dL; 3) patients without CAD, but an LDL-C level ≥300 mg/dL. © 1996 Wiley-Liss, Inc.     

The relationship between nonfasting and fasting lipid measurements in patients with or without type 2 diabetes mellitus receiving treatment with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors

BACKGROUND: Studies have confirmed a lack of patient and physician adherence to the revised National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines. These guidelines state that lipid panels should be obtained while the patient is in the fasting state. However, this restriction may limit the ordering of these tests and thus decrease the number of patients on drug therapy and the number treated until goal cholesterol levels are reached. Evidence shows that testing in the nonfasting state may not be clinically or significantly different from testing in the fasting state in identifying patients at risk for a future cardiovascular event. OBJECTIVES: The purpose of this study was to determine whether a relationship exists between nonfasting and fasting lipid values in diabetic or nondiabetic patients that will permit the more ready identification of patients who require treatment to meet NCEP ATP III guidelines. A secondary goal was to determine whether diabetic patients who appear to have reached goal cholesterol levels in the fasting state meet those goals when the non-high-density lipoprotein cholesterol (HDL-C) levels are measured in the nonfasting state. METHODS: This observational study was conducted at Androscoggin Cardiology Associates (Auburn, Maine). Patients with hyperlipidemia receiving statin therapy whose doses had not changed for > or =2 months were enrolled. For all patients, nonfasting and fasting lipid panels (total cholesterol, triglycerides [TGs], and HDL-C) were calculated, whereas low-density lipoprotein cholesterol (LDL-C)levels were measured directly. The direct LDL-C method was used to determine the variance of the calculated LDL-C from the actual value. RESULTS: One hundred consecutive hyperlipidemic patients were tested. Patients included 70 men and 30 women, with a mean (SD) age of 66.2 (12.0) years(range, 24-93 years). Eighteen patients had type 2 diabetes mellitus (DM). Non-fasting TG, HDL-C, and LDL-C levels were able to identify almost all patients who did not meet ATP III guidelines in terms of cholesterol levels (95%, 100%, and 95%, respectively). No predictive differences were found, regardless of whether the patients had type 2 DM. For the total population, statistically significant differences were found between calculated nonfasting and fasting measurements for mean (SD)LDL-C levels (90.2 [24.8] mg/dL vs 99.7 [26.1] mg/dL, respectively; P < 0.001).The regression equation was fasting LDL-C = 22.7 + 0.854 x nonfasting LDL-C.A nonfasting LDL-C level >130 mg/dL predicted a fasting LDL-C level >100 mg/dL(95% CI, -12.79 to -6.24), and a nonfasting LDL-C level >130 mg/dL predicted cases of fasting LDL-C level >100 mg/dL (95% CI, -5.79 to -1.35). CONCLUSIONS: In this study population, nonfasting TG, HDL-C, and LDL-C levels successfully identified almost all patients who did not meet ATP III guidelines for cholesterol levels. No clinically significant difference was found in diabetic or nondiabetic patients.     

Management of hyperlipidemia in patients with vascular disease.

Atherosclerosis contributing to cardiovascular disease is the leading cause of death in the United States. It is also the major cause of peripheral arterial disease (PAD). Although there is substantial evidence that aggressive treatment of hyperlipidemia improves the outcome of patients with coronary artery disease (CAD), relatively little attention has been directed toward lipid control in patients with PAD. The National Cholesterol Education Program (NCEP) has established guidelines for treatment of lipids in patients with atherosclerotic disease. The purpose of this study was to determine the effectiveness of current lipid management practices in patients electively admitted for peripheral vascular surgery and to explore methods to improve compliance with NCEP guidelines. The past medical/surgical history, risk factors for atherosclerosis, and medication regimen including lipid medications were obtained from a retrospective review of the medical records of 105 consecutive patients scheduled for an elective vascular procedure. Lipid profiles were obtained as part of their routine preoperative assessment and the results were compiled and compared with established NCEP guidelines to determine the level of compliance in our PAD population. Eighty-five of the 105 patients had lipid profiles recorded in the medical record. Only 42% of patients were at or below the recommended goal of less than 100 mg/dL for low-density lipoprotein (LDL). Greater than half of patients had previous diagnosis of atherosclerosis or had previous bypass including coronary artery bypass surgery. Despite the strong emphasis on lipid reduction, especially LDL cholesterol, only a minority of patients admitted for peripheral vascular surgery were at the recommended NCEP goal. More aggressive evaluation and treatment of lipid disorders in patients with PAD seems warranted.     

Cholesterol-lowering drugs bring benefits to high-risk populations even when LDL is normal

The Heart Protection Study (HPS) results were presented shortly after the National Cholesterol Education Program released the third report of clinical practice guidelines for the evaluation and management of elevated cholesterol in adults. Both the guidelines and the HPS results support an aggressive approach to managing high-risk individuals. The HPS showed that cardiovascular events and mortality were reduced in high-risk patients taking simvastatin regardless of baseline low-density lipoprotein (LDL) cholesterol levels. Some of these patients would not have met criteria for drug treatment according to the guidelines. The conclusion was that all high-risk patients with LDL > or = 100 mg/dL should be treated with drug therapy with the goal of reducing LDL to < 100 mg/dL.     

A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia

OBJECTIVE: Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone. RESEARCH DESIGN AND METHODS: We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals. RESULTS: Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005). CONCLUSIONS: Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.     

Assessment of compliance with lipid guidelines in an academic medical center

BACKGROUND: The importance of achieving a low-density lipoprotein cholesterol (LDL-C) level less than 100 mg/dL in patients with coronary artery disease (CAD) or cerebrovascular disease (CVD) is well established. Emerging evidence supports the recognition and management of secondary lipid goals, high-density lipoprotein cholesterol (HDL-C) level greater than 40 mg/dL, and triglyceride level less than 150 mg/dL. OBJECTIVE: To evaluate whether inpatient services within an academic setting were achieving/addressing primary and secondary lipid goals in patients with established CAD or CVD. METHODS: Patients with a discharge diagnosis of acute myocardial infarction, myocardial revascularization procedures, and/or ischemic stroke were identified. A retrospective chart review was done to assess adherence to the American Heart Association (AHA)/American College of Cardiology (ACC) guidelines for lipid management. RESULTS: On average, 63% of patients with CAD or CVD had a lipid panel assessed during their hospitalization. Of the patients who had a fasting lipid panel checked, only 40% (72/178) had an LDL-C level less than 100 mg/dL. Of those patients, only 31% (22) also had an HDL-C level greater than 40 mg/dL. Even fewer patients (24%; 17) met both primary and secondary goals. Of the 287 patients included in the study, 69% (199) were prescribed a statin, 3% (9) a fibrate, and 3% (8) niacin on discharge. CONCLUSIONS: Few patients with CAD or CVD met the AHA/ACC goals for lipid management, yet a significant number were not prescribed appropriate lipid-lowering therapy at discharge. This finding strongly suggests that more awareness in this area is needed.     

A crossover comparison of the efficacy and safety of lovastatin and gemfibrozil in the treatment of hyperlipidemic organ transplant recipients.

Hypercholesterolemia is associated with accelerated atherosclerosis in transplant recipients. It has been notoriously difficult to treat pharmacologically due to the complex interactions that occur with lipid-lowering drugs and immunosuppressive therapies. The purpose of the current study was to compare the efficacy and safety of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (lovastatin, 20 mg/d) with a fibric acid derivative (gemfibrozil, 600 mg twice a day). We used a randomized, crossover design in 18 solid organ transplant recipients who followed the National Cholesterol Education Program Adult Treatment Guidelines diet for 8 weeks and had persistent elevations of total cholesterol (>240 mg/dL). Each patient received each therapy for a minimum of 8 weeks (mean 14.2 +/- 2.4, range 8-20 weeks). The participants had stable allograft function and were treated with a standard immunosuppressive regimen containing cyclosporine, prednisone, and azathioprine. Lovastatin therapy reduced the mean total cholesterol by 15.5% (271.9 mg/dL to 229.9 mg/dL; p = 0.02) and the mean low-density lipoprotein (LDL) cholesterol by 22.7% (178.2 mg/dL to 137.8 mg/dL; p = 0.07). There were no significant changes in high-density lipoprotein (HDL) cholesterol or triglycerides. Conversely, when these same patients were treated with gemfibrozil, the mean total cholesterol decreased by 7.9% (271.9 mg/dL to 250.5 mg/dL; p = NS) and the LDL cholesterol decreased by 5.1% (178.2 mg/dL to 169.1 mg/dL; p = NS). In addition, the mean triglyceride concentration decreased significantly by 46.1% (234.0 mg/dL to 126.3 mg/dL; p = 0.002) and the mean HDL cholesterol increased 15.4% (48.8 mg/dL to 56.3 mg/dL; p = 0.09). In all patients, the serum creatinine, hepatocellular enzymes, and creatinine phosphokinase remained stable. Lovastatin was discontinued in three patients for myalgias, one patient with unexplained anemia, and one patient with parasthesias. These results suggest that lovastatin and gemfibrozil are both safe and efficacious in transplant patients. However, neither therapy alone completely corrects abnormalities of high LDL cholesterol and low HDL cholesterol in transplant recipients.     

STATT: a titrate-to-goal study of simvastatin in Asian patients with coronary heart disease. Simvastatin Treats Asians to Target.

BACKGROUND: Most published studies on the use of lipid-lowering agents to treat hypercholesterolemia have focused on Western populations, with few data on Asian populations. OBJECTIVE: The Simvastatin Treats Asians to Target (STATT) study used a titrate-to-goal protocol to evaluate the efficacy and tolerability of simvastatin 20 to 80 mg/d in the treatment of Asian patients with coronary heart disease. METHODS: This was a multicenter, open-label, uncontrolled, 14-week study in patients with coronary heart disease and serum low-density lipoprotein cholesterol (LDL-C) levels of 115-180 mg/dL and triglyceride levels of < or = 400 mg/dL. The dose of simvastatin was titrated from 20 to 80 mg/d to achieve the National Cholesterol Education Program (NCEP) LDL-C target of < or = 100 mg/dL. The primary efficacy measure was the percentage of patients achieving the NCEP target. Among secondary measures were the percentage of patients achieving European Society of Cardiology/European Atherosclerosis Society/European Society of Hypertension target LDL-C levels of < or = 115 mg/dL and the percentage change from baseline in lipid parameters. Tolerability was assessed in terms of the overall incidence of adverse experiences and the incidences of the most commonly reported adverse experiences. RESULTS: The intent-to-treat analysis included 133 Asian patients (93 men, 40 women; mean age, 59.5 years), of whom 125 completed 14 weeks of therapy. Their mean blood pressure was 130.2/79.4 mm Hg. Overall, 104 (78.2%) patients treated with simvastatin achieved LDL-C levels < or = 100 mg/dL at week 14, and 125 (94.0%) achieved this target at some point during the study. Similarly, 122 (91.7%) patients achieved an LDL-C level < or = 115 mg/dL at week 14, and 130 (97.7%) achieved this target at some point during the study. Treatment with simvastatin had favorable effects on the lipid profile, producing significant percentage changes from baseline in all parameters (P < 0.001). Simvastatin was well tolerated across the dose range. Overall, 40 patients (30.1%) had > or = 1 clinical adverse experience. Only 14 (10.5%) had adverse experiences that were possibly, probably, or definitely related to study drug; none of these experiences were considered serious. The most common adverse experiences (> or = 3% incidence) were abdominal pain (6%); chest pain (5%); dizziness (4%); and asthenia/fatigue, fibromyalgia, headache, insomnia, and upper respiratory tract infection (3% each). No new or unexpected adverse experiences were seen at the higher doses. CONCLUSIONS: Simvastatin was effective and well tolerated at doses of 20, 40, and 80 mg/d in Asian patients with coronary heart disease. Titration enabled the majority to achieve target LDL-C levels of < or = 100 mg/dL.     

Low-density lipoprotein apheresis for the treatment of refractory hyperlipidemia

The advent of treatment with 3-hydroxy-3-methylglutaryl coenzyme A inhibitors has meant that, with a combination of diet and drug therapy, adequate control of serum cholesterol concentrations can be achieved in most patients with hypercholesterolemia. However, some patients, primarily those with familial hypercholesterolemia (FH), may require additional therapy to lower their cholesterol levels. In recent years, low-density lipoprotein (LDL) apheresis has emerged as an effective method of treatment in these patients. The criteria for commencement of LDL apheresis are LDL cholesterol levels of 500 mg/dL or higher for homozygous FH patients, 300 mg/dL or higher for heterozygous FH patients in whom medical therapy has failed, and 200 mg/dL or higher for heterozygous FH patients with documented coronary disease and in whom medical therapy has failed. In addition to cholesterol lowering in patients with FH, other indications for LDL apheresis are emerging. These include its use in the treatment of graft vascular disease in patients receiving cardiac transplants as well as in the treatment of certain glomerulonephritides. This review examines the role of LDL apheresis in the management of lipid disorders and the evidence available to support its use in clinical practice.     

Dietary therapy for children with hypercholesterolemia

Accumulating evidence clearly shows that atherosclerosis begins in youth. The National Cholesterol Education Program (NCEP) has recommended that children at high risk of developing coronary artery disease as adults be screened so that those with elevated low-density lipoprotein (LDL) cholesterol levels can be treated, primarily by modification of diet. The initial approach to these youthful patients is to use the NCEP step I diet. This diet provides calories and nutrients that support normal growth and development, but limits saturated fat and total fat intake to no more than 10 and 30 percent of total calories, respectively, and cholesterol intake to no more than 100 mg per 1,000 kcal per day, to a maximum of 300 mg. If the goal of reducing the LDL cholesterol level to below 130 mg per dL (3.35 mmol per L) is not achieved, the more restrictive step II diet should be initiated. However, the step II diet may not provide sufficient calories and nutrients to support normal growth and development; therefore, trained nutritionists may be required to effectively manage a child on this diet.