Sex disparities in treatment of cardiac risk factors in patients with type 2 diabetes

OBJECTIVE: Diabetes eliminates the protective effect of female sex on the risk of coronary heart disease (CHD). We assessed sex differences in the treatment of CHD risk factors among patients with diabetes. RESEARCH DESIGN AND METHODS: A cross-sectional analysis included 3,849 patients with diabetes treated in five academic internal medicine practices from 2000 to 2003. Outcomes were stratified by the presence of CHD and included adjusted odds ratios (AORs) that women (relative to men) were treated with hypoglycemic, antihypertensive, lipid-lowering medications or aspirin (if indicated) and AORs of reaching target HbA(1c), blood pressure, or lipid levels. RESULTS: Women were less likely than men to have HbA(1c) <7% (without CHD: AOR 0.84 [95% CI 0.75-0.95], P = 0.005; with CHD: 0.63 [0.53-0.75], P < 0.0001). Women without CHD were less likely than men to be treated with lipid-lowering medication (0.82 [0.71-0.96], P = 0.01) or, when treated, to have LDL cholesterol levels <100 mg/dl (0.75 [0.62-0.93], P = 0.004) and were less likely than men to be prescribed aspirin (0.63 [0.55-0.72], P < 0.0001). Women with diabetes and CHD were less likely than men to be prescribed aspirin (0.70 [0.60-0.83], P < 0.0001) or, when treated for hypertension or hyperlipidemia, were less likely to have blood pressure levels <130/80 mmHg (0.75 [0.69-0.82], P < 0.0001) or LDL cholesterol levels <100 mg/dl (0.80 [0.68-0.94], P = 0.006). CONCLUSIONS: Women with diabetes received less treatment for many modifiable CHD risk factors than diabetic men. More aggressive treatment of CHD risk factors in this population offers a specific target for improvement in diabetes care.     

Twelve-week, multicenter, randomized, open-label comparison of the effects of rosuvastatin 10 mg/d and atorvastatin 10 mg/d in high-risk adults: a DISCOVERY study

BACKGROUND: Guidelines for the prevention of coronary heart disease (CHD) advocate reductions in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels as the primary goals. However, approximately 50% to 60% of patients fail to reach recommended cholesterol goals. OBJECTIVES: The primary objective of this Direct Statin Comparison of LDL-C Values: An Evaluation of Rosuvastatin Therapy Compared with Atorvastatin (DISCOVERY) trial was to compare the efficacy of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors rosuvastatin calcium and atorvastatin calcium in achieving the 1998 Second Joint Task Force (JTF) of European and Other Societies on Coronary Prevention target for LDL-C. Secondary objectives included comparing the efficacy of rosuvastatin and atorvastatin in achieving the 1998 JTF-recommended goal for TC and modifying other lipid levels, and to compare the tolerability of the 2 statins. METHODS: This 12-week, randomized, open-label, 2-arm, parallel-group trial was conducted at 210 centers in Finland, Iceland, and Ireland. Patients aged > or =18 years with a high risk for CHD and primary hypercholesterolemia (LDL-C >3.5 mmol/L [>135 mg/dL]) were randomized (2:1) to receive rosuvastatin 10 mg or atorvastatin 10 mg PO OD for 12 weeks. Before randomization, statin-naive patients underwent 6 weeks of dietary counseling, whereas patients receiving treatment with a starting dose of another lipid-lowering therapy but with an LDL-C level >3.1 mmol/L (>120 mg/dL) were switched to study drug immediately after they were determined eligible for the study Patients were assessed for fasting lipid levels at weeks 0 and 12, and the proportions of patients attaining 1998 and 2003 JTF lipid goals (1998: LDL-C, <3.0 mmol/L [<116 mg/dL]; TC, <5.0 mmol/L [<193 mg/dL]; 2003: LDL-C, <2.5 mmol/L [<97 mg/dL]; TC, <4.5 mmol/L [<174 mg/dL]) were calculated. Tolerability was monitored for the 12-week study and for an additional 36-week optional extension period. RESULTS: One thousand twenty-four patients were randomized to treatment (568 men, 456 women; mean age, 60.7 years). Patient demographic characteristics were similar between the 2 treatment groups. The efficacy analysis consisted of 911 patients (504 men, 407 women; mean age, 60.7 years; mean body weight, 82.4 kg); 627 received rosuvastatin and 284 received atorvastatin. Compared with atorvastatin, rosuvastatin was associated with significantly greater reductions in LDL-C and TC (both, P < 0.05), and with a significantly greater increase in high-density lipoprotein cholesterol level (P < (105). A greater proportion of patients in the rosuvastatin group compared with the atorvastatin group reached the 1998 goals for LDL-C (83.4% vs 683%; P < 0.001) and TC (76.4% vs 59.5%; P < 0.001). Also, compared with the atorvastatin group, greater proportions of patients in the rosuvastatin group achieved the 2003 JTF goals for LDL-C and TC (both, P < 0.001). Both agents were well tolerated: serious drug-related events were observed in < or =3.0% of patients in each group, and no clinically significant differences were found between the 2 treatment groups. CONCLUSIONS: In this study of selected patients at high risk for CHD and with primary hypercholesterolemia, rosuvastatin 10 mg/d for 12 weeks was associated with significantly greater reductions in LDL-C and TC levels compared with atorvastatin 10 mg/d. Furthermore, significantly more patients receiving rosuvastatin achieved the 1998 and 2003 JTF-recommended lipid targets compared with those receiving atorvastatin. Both agents were well tolerated.     

Status of lipid-lowering therapy prescribedbased on recommendations in the 2002 report of the Japan Atherosclerosis Society Guideline for Diagnosis and Treatment of Hyperlipidemia in Japanese Adults: A study of the Japan Lipid Assessment Program (J-LAP)

Background:

In its 1997 Guideline for Diagnosis and Treatment of Hyperlipidemia in Japanese Adults and subsequent revisions, the Japan10 Atherosclerosis Society (JAS) recommends serum lipid management goals (SLMGs) based on a coronary heart disease (CHD) risk classification. A literature search revealed that the status of lipid-lowering therapy based on the current JAS recommendations in Japan has not been assessed.

Objective:

The aim of this study was to evaluate the efficacy of current lipid-lowering 10 regimens, and to provide the best possible therapeutic strategies for patients with hyperlipidemia by identifying risk factors for the development of CHD, based on the current JAS recommendations.

Methods:

This multicenter, retrospective study was conducted using data 10 from patients under the care of physicians at 12,500 randomly selected institutions across Japan. Physicians received a survey concerning lipid-lowering therapy, on which each physician provided data from 10 consecutive adult patients with hyperlipidemia who had been prescribed lipid-lowering therapy for at least 3 months before the survey was administered, and who were undergoing routine follow-up on an outpatient basis. Physicians provided patients' demographic and clinical data, including JAS-defined CHD risk classification coronary risk factors and pre- and posttreatment (after ≥3 months) serum lipid levels, and the types and dosages of drugs in patients' current and prior treatment regimens. These data were used to assess the efficacy of lipid-lowering regimens and rates of patients achieving the SLMGs recommended by the JAS.

Results:

A total of 2540 physicians participated in the survey, and data from 10 24,893 Japanese patients (mean [SD] age, 65.8 [10.5] years) with hyperlipidemia were included in the study. Patients with familial hyperlipidemia (845/24,893 [3.4%]) were excluded from most of the analyses, leaving 24,048 patients with primary hyperlipidemia. The most prevalent coronary risk factors included age (21,902 [91.1%]), hypertension (14,275 [59.4%]), diabetes mellitus type 2 and/or impaired glucose tolerance (6346 [26.4%]), and smoking (3841 [16.0%]). A total of 20,948 patients (87.1%) had a CHD risk classification of B (ie, ≥1 coronary risk factor but no history of CHD). At the time of the survey, the lipid-lowering regimens of 22,080 patients (91.8%) included a statin. The rates of achievement of SLMGs were as follows: total cholesterol (TC), 12,659/23,840 patients (53.1%); low-density lipoprotein cholesterol (LDL-C), 14,025/22,121 (63.4%); high-density lipoprotein cholesterol, 19,702/21,279 (92.6%); and triglycerides (TG), 14,892/ 23,569 (63.2%). TC and LDL-C goals were achieved by most patients (≥61.1%) in risk categories A, B1, and B2 (ie, 0-2 coronary risk factors; low to moderate risk) but by a low percentage of patients (≤45.4%) in risk categories B3, B4, and C (ie, ≥3 coronary risk factors or history of CHD; high risk). In the high-risk group (n = 10,515), the TC goal was achieved by 4059 patients (38.6%). The TC and LDL-C goals were achieved by significantly higher percentages of patients prescribed atorvastatin (5133/7928 [64.7%] and 5487/7426 [73.9%], respectively) compared with the rates of patients prescribed any other statin at the recommended starting doses (all, P < 0.05).

Conclusions:

The results of this study of Japanese patients undergoing lipid-lowering 10 therapy for the prevention of CHD, prescribed based on the recommendations in the JAS guideline, suggest insufficient reduction of TC, LDL-C, and TG in patients at high risk for CHD and the need for more aggressive lipid-lowering therapy in such patients.     

A 52-week,multicenter, randomized,parallel-group,double-blind,double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: the treat-to-target (3T) study

BACKGROUND: Guidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target. OBJECTIVE: The purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C or=4.0 mmol/L (>or=155 mg/dL), were randomized in a 1:1 ratio to receive once-daily oral treatment with 20 mg atorvastatin or 20 mg simvastatin. Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National Cholesterol Education Program level of LDL-C (相似文献   

Lipidprofil und Therapiestatus in der Sekundärprävention bei Hochrisiko-Patienten mit klinisch manifester Arteriosklerose und/oder Diabetes mellitus: Das Hospital Screening Projekt (HSP) in Österreich

Cardiovascular disease is the major cause of morbidity and premature death in most European populations. Due to its prominent role as a risk factor for cardiovascular mortality, lowering of low density lipoprotein cholesterol (LDL-C) levels is the main goal for management of dyslipidemia. To evaluate lipid profiles and management of high risk patients with hyperlipidemia, we performed an observational study in 20 Austrian Departments of Medicine specialized in cardiology, diabetes and/or metabolism from July 2006 to February 2007. Out of 9152 patients [age (mean +/- SD): women 69 +/- 13, men 65 +/- 12 years) 6838 were considered at "very high risk" (group 1; LDL-C: 99 +/- 38 mg/dl) and 2314 at "high risk" (group 2; LDL-C: 108 +/- 39 mg/dl), respectively. Of 4886 patients on statins, 48% of did not reach their LDL-C goals (<70 mg/dl and <100 mg/dl for group 1 and 2, respectively). In 68% of these patients statin therapy was not intensified subsequently. Among patients without lipid-lowering drugs at study entry, 62% did not meet their targets, and despite treatment in the center 1555 of these patients (58%) remained without medication. With regard to national and international guidelines, there is still a need to improve the clinical practice of lowering LDL-C for secondary prevention in high risk patients in Austria.     

Mixed dyslipidemia among patients using lipid-lowering therapy in French general practice: an observational study

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) are associated with an increased incidence of coronary heart disease (CHD). However, limited data are available about the prevalence of dyslipidemias related to LDL-C, HDL-C, and TGs among French patients treated with lipid-lowering agents. OBJECTIVE: This paper describes the prevalence of various types of dyslipidemias among patients treated with lipid-lowering agents in French general practice. METHODS: This was a cross-sectional, observational study conducted using retrospective data collection at the time of enrollment. Eligible patients were those treated pharmacologically for dyslipidemia in the Cegedim Strategic Data general practice network. Fasting lipid values and cardiovascular (CV) risk factors were gathered by investigators using an ad hoc questionnaire. European guidelines were used to define various types of dyslipidemias. Polytomous logistic regression was used to assess the associations between different dyslipidemias and diabetes mellitus, a history of CHD, and the number of CV risk factors. RESULTS: A total of 946 patients had a complete lipid profile and valid data for determining CV risk status. The mean (SD) age of these patients was 64.0 (9.9) years, and 55.7% of the patients were men. At least 1 abnormality in LDL-C, HDL-C, or TGs was present in 791 (83.6 %) of the 946 patients. The rates of elevated LDL-C, low HDL-C, and elevated TGs were 73.2%, 16.9%, and 30.3%, respectively (these groups are not mutually exclusive). Among those who did not reach the LDL-C goal, 38.7% had dyslipidemias with low HDL-C, elevated TGs, or both. Compared with having a normal lipid profile, each additional CV risk factor increased the likelihood of the following types of dyslipidemias: low HDL-C and/or elevated TGs, but normal LDL-C (odds ratio [OR], 1.36; 95% CI, 1.03-1.79); elevated LDL-C and TGs, but normal HDL-C (OR, 1.58; 95% CI, 1.24-2.02); and all 3 lipid abnormalities (OR, 1.54; 95% CI, 1.10-2.14). Patients with diabetes had a similarly increased risk of mixed dyslipidemias, whereas patients with a history of CHD did not. CONCLUSIONS: Among these patients treated with lipid-lowering agents, 38.7% had mixed dyslipidemias, including low HDL-C, elevated TGs, both low HDL-C and elevated TGs, or all 3 lipid abnormalities. Patients with a greater number of nonlipid CV risk factors or with diabetes had a significantly increased risk of mixed dyslipidemias involving elevated TGs and/or low HDL-C in addition to elevated LDL-C.     

Prospective,noninterventional, uncontrolled,open-chart,pharmacoepidemiologic study of prescribing patterns for lipid-lowering drugs at a tertiary care teaching hospital in North India

BACKGROUND: The guidelines for management of dyslipidemia released by the US National Cholesterol Education Program (NCEP) have been questioned for their relevance in the South Asian Indian populations because these populations are reported to have significantly different lipoprotein parameters and atherogenic risk factors than Western populations. OBJECTIVE: The aim of this study was to determine current prescribing patterns for lipid-lowering drugs (LLDs) adopted by physicians in North India. METHODS: This prospective, noninterventional, uncontrolled, open-chart, pharmacoepidemiologic study was conducted from June 2000 to August 2000 at a tertiary care hospital in North India and included 200 dyslipidemic patients. The pattern of prescribing LLDs was recorded, along with the serum levels of lipid parameters-total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and lipoprotein(a) (Lp[a])-at the time of initiating LLD therapy and compared with the 1993 NCEP-II therapeutic guidelines for dyslipidemia management. RESULTS: The mean (SD) levels of lipid parameters in the study population were as follows: TC, 223.2 (21.5) mg/dL; TG, 258.4 (61.3) mg/dL; LDL-C, 131.6 (26.5) mg/dL; HDL-C, 39.8 (8.9) mg/dL; and Lp(a), 44.8 (26.8) mg/dL. The LLDs prescribed were fibrates (53.5%) and statins (46.5%). Forty percent of patients prescribed LLDs did not meet the NCEP-II criteria for initiation of LLD therapy. CONCLUSIONS: Considerable differences in prescribing patterns of LLDs were observed compared with the then-prevalent NCEP-II guidelines. However, due to the abnormally high serum Lp(a) levels present in the average dyslipidemia profile in South Asian Indian populations, this pattern was in accordance with the specific recommendations made for these populations, as well as with the 2001 NCEP-III guidelines.     

A multicenter, randomized, double-blind clinical trial comparing the low-density lipoprotein cholesterol-lowering ability of lovastatin 10, 20, and 40 mg/d with fluvastatin 20 and 40 mg/d

BACKGROUND: The available statin drugs have similar pharmacodynamic properties but are not equal in low-density lipoprotein cholesterol (LDL-C)-lowering efficacy. OBJECTIVE: The aim of this study was to compare the effects of lovastatin and fluvastatin in lowering LDL-C. METHODS: This was a prospective, randomized, double-blind study of patients aged >20 years with primary hypercholesterolemia conducted at 44 clinical sites across the United States. After a 6-week National Cholesterol Education Program (NCEP) Step I diet lead-in period in patients taking lipid-lowering drugs at screening, patients were randomized to receive lovastatin 10, 20, or 40 mg/d or fluvastatin 20 or 40 mg/d (the doses available at the time the study was conducted) for 6 weeks. Patients not taking lipid-lowering drugs at screening and who had been following the Step I diet for at least 6 weeks proceeded to the treatment phase. All patients received instruction for a Step I diet, which they followed throughout the treatment phase. After the treatment period, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides were measured, and TC:HDL-C and LDL-C:HDL-C ratios were calculated. RESULTS: A total of 838 patients (476 men, 362 women; mean [SD] age, 59 [12] years) were included in the study. Lovastatin 20 and 40 mg/d significantly reduced mean LDL-C compared with the same dosages of fluvastatin. TC and the LDL-C:HDL-C ratio decreased more with lovastatin than with fluvastatin at a given dose level. Approximately 50% of patients treated with lovastatin 20 and 40 mg/d compared with approximately 25% treated with fluvastatin 20 and 40 mg/d reached NCEP Adult Treatment Panel II LDL-C goals. CONCLUSION: In this small study population of patients with primary hypercholesterolemia taking lipid-lowering drugs, short-term (6-week) treatment with lovastatin was more efficacious than fluvastatin in lowering cholesterol levels and reaching LDL-C treatment goals.     

Benefits of early lipid-lowering intervention in high-risk patients: the lipid intervention strategies for coronary patients study

BACKGROUND: There is controversy about whether lipid-lowering pharmacotherapy should be initiated immediately after an acute coronary event or only after diet and lifestyle changes have proved inadequate. OBJECTIVE: This study, known as the Lipid Intervention Strategies for Coronary Patients Study, compared the efficacy of immediate versus deferred simvastatin treatment in conjunction with dietary advice about reducing lipid levels in hypercholesterolemic patients with acute coronary syndromes. METHODS: This randomized, open-label, parallel-group study included 151 hypercholesterolemic (low-density lipoprotein cholesterol [LDL-C] >3.0 mmol/L) men and women aged 35 to 75 years. Within 4 days of diagnosis of acute myocardial infarction (MI) or unstable angina pectoris, all patients received dietary advice from a specially trained nurse. Subsequently, patients were randomized to 2 treatment groups: 1 group received immediate treatment with simvastatin 40 mg/d; patients in the other group received simvastatin 40 mg/d after 3 months only if their LDL-C remained >3.0 mmol/L. Results: The immediate-simvastatin group (n = 73) and the deferred-simvastatin group (n = 78) were balanced with respect to baseline characteristics. Of the 151 patients, 25% were women, 25% had concomitant hypertension, and 75% had a diagnosis of MI on enrollment. At 3 months, 90% of the patients receiving dietary advice plus immediate simvastatin treatment had achieved the recommended European target LDL-C level of <3.0 mmol/L, compared with 7% of those treated with diet alone. By 6 months, when 92% of the study participants were receiving simvastatin 40 mg/d, the proportion of patients achieving target LDL-C levels was 92% in the group that received immediate simvastatin therapy and 81% in the group that received deferred simvastatin therapy. The reductions in LDL-C (42%-48%) were considered to be clinically comparable between the 2 groups at 12 months. CONCLUSIONS: On the basis of these results, we concluded that few patients with hypercholesterolemia and acute coronary syndromes reach the recommended European target LDL-C level of <3.0 mmol/L with dietary advice alone. However, early treatment with simvastatin 40 mg/d combined with dietary advice and follow-up at a dedicated outpatient clinic specializing in coronary heart disease resulted in 9 out of 10 patients reaching a recommended target LDL-C level of <3.0 mmol/L. Initiation of simvastatin therapy while a patient is hospitalized may increase the likelihood of the patient's lipid levels being managed according to current recommendations after he or she is discharged.     

Adherence of hospital-based cardiologists to lipid guidelines in patients at high risk for cardiovascular events (2L registry)

Objectives  

According to various national and international guidelines, the target LDL-C level is <100 mg/dl for patients with established coronary heart disease (CHD) or CHD risk equivalent (CE). We aimed to investigate aspects of the lipid-lowering management of patients at high cardiovascular risk in-hospital care and the achievement of target values.     

Management of dyslipidemias in the age of statins

Evidence for the effectiveness of lipid-lowering therapy in reducing CHD risk continues to emerge. In primary prevention, clinical trials have demonstrated a benefit for middle-aged, high-risk men with high LDL cholesterol and, more recently, for men and women with "average" LDL and low HDL cholesterol. Although low HDL cholesterol, small dense LDL particles, elevated lipoprotein (a), elevated apolipoprotein B, and the dyslipidemia of the metabolic syndrome pose an increased in CHD risk in some patients, the risk reduction with lipid-lowering therapy has not been fully investigated. The CHD risk of isolated hypertriglyceridemia remains uncertain. Very high triglyceride levels, however, should be treated to prevent pancreatitis. A lipid-lowering diet and other appropriate lifestyle changes constitute safe advice for all patients with dyslipidemia. In initiating pharmacologic therapy, physicians should view potential risk reduction in the context of a patient's overall CHD risk. The selection of particular medications can be individualized, considering effectiveness evidence from clinical trials, lipid-lowering potency, adverse effects, drug interactions, costs, and patient preferences.     

Efficacy of atorvastatin for achieving cholesterol targets after LDL-cholesterol based dose selection in patients with type 2 diabetes

We analyzed the feasibility of an intensive lipid-lowering strategy based on a starting dose of atorvastatin according to baseline and target low-density lipoprotein cholesterol (LDL-C) level (<2.6 mmol/L) in 202 statin-na?ve patients with type 2 diabetes within 24 weeks. They were assigned to receive a daily dosage of atorvastatin based on their initial LDL-C levels. The primary endpoint was the proportion of patients achieving the LDL-C goal after 24 weeks of treatment. No changes were made in prescribed atorvastatin dosage. At the study end, 66.5% of the 188 patients completing the trial reached the LDL-C target (75%, 67%, 58% and 59% with 10, 20, 40 and 80 mg per day of atorvastatin, respectively) reached LDL-C target. Atorvastatin reduced the levels of total cholesterol, LDL-C, high density lipoprotein cholesterol (HDL-C) and triglycerides by 29%, 35%, 3% and 22%, respectively, and all statin doses were well tolerated. Thus, individualizing the starting dose of atorvastatin according to baseline and target LDL-C levels, allowed a high proportion of type 2 diabetic patients to achieve the target within 24 weeks.     

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.     

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.     

Rosuvastatin versus atorvastatin in achieving lipid goals in patients at high risk for cardiovascular disease in clinical practice: A randomized, open-label, parallel-group, multicenter study (DISCOVERY Alpha study)

Background:

The majority of clinical trials investigating the clinical benefits of lipid-lowering therapies (LLTs) have focused on North American or western and nothern European populations. Therefore, it is timely to confirm the efficacy of these agents in other patient populations in routine clinical practice.

Objective:

The aim of the Direct Statin COmparison of low-density lipoprotein cholesterol (LDL-C) Values: an Evaluation of Rosuvastatin therapY (DISCOVERY) Alpha study was to compare the effects of rosuvastatin 10 mg with those of atorvastatin 10 mg in achieving LDL-C goals in the Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice guidelines.

Methods:

This randomized, open-label, parallel-group study was conducted at 93 centers in eastern Europe (Estonia, Latvia, Romania, Russia, Slovenia), Central and South America (Chile, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama), and the Middle East (Israel, Kuwait, Saudi Arabia, United Arab Emirates). Male and female patients aged ≥18 years with primary hypercholesterolemia (LDL-C level, >135 mg/dL if LLT-naive or ≥120 mg/dL if switching statins; triglyceride [TG] level, <400 mg/dL) and a 10-year coronary heart disease (CHD) risk >20% or a history of CHD or other established atherosclerotic disease were eligible for inclusion in the study. Patients were randomly assigned to receive rosuvastatin 10-mg or atorvastatin 10-mg tablets QD for 12 weeks. No formal statistical analyses or comparisons were performed on lipid changes between switched and LLT-naive patients because of the different lipid inclusion criteria for these patients. The primary end point was the proportion of patients achieving 1998 European LDL-C goals after 12 weeks of treatment. A subanalysis was performed to assess the effects of statins in patients who had received previous statin treatment versus those who were LLT-naive. Tolerability was assessed using laboratory analysis and direct questioning of the patients.

Results:

A total of 1506 patients (52.1% women, 47.9% men; mean [SD] age, 58.2 [10.8] years) participated in the study (rosuvastatin, 1002 patients; atorvastatin, 504 patients; previous LLT, 567 patients). A significantly higher proportion of patients achieved 1998 European LDL-C goals after 12 weeks with rosuvastatin 10 mg than with atorvastatin 10 mg (72.5% vs 56.6%; P < 0.001). Similarly, more patients achieved the 2003 European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 10 mg (57.5% vs 39.2%). Rosuvastatin 10 mg was associated with a significantly greater change in LDL-C levels compared with atorvastatin 10 mg, in patients who were LLT-naive (LDL-C: −44.7% vs −33.9%; P < 0.001) and in patients who had received previous LLT (LDL-C: −32.0% vs −26.5%; P = 0.006). TG levels were also decreased with rosuvastatin 10 mg and atorvastatin 10 mg, although there was no significant difference between treatments. Similarly, there was no significant difference in the increase in high-density lipoprotein cholesterol levels between treatments. The most common adverse events overall were headache 16/1497 (1.1%), myalgia 10/1497 (0.7%), and nausea 10/1497 (0.7%).

Conclusions:

In this study in patients with primary hypercholesterolemia in clinical practice, greater reductions in LDL-C levels were achieved with a starting dose (10 mg) of rosuvastatin compared with atorvastatin 10 mg, with more patients achieving European LDL-C goals. Both treatments were well tolerated     

A comparison of the efficacy and tolerability of titrate-to-goal regimens of simvastatin and fluvastatin: a randomized, double-blind study in adult patients at moderate to high risk for cardiovascular disease

BACKGROUND: Use of cholesterol-lowering regimens has been shown to reduce the risk of coronary heart disease (CHD), both in primary and secondary prevention. However, there have been few studies of the relative benefits and risks of the various cholesterol-lowering agents in patient groups with specific risk factors for CHD. OBJECTIVE: The primary goal of this study was to compare the proportions of adult patients with primary hypercholesterolemia and a moderate to high risk for CHD achieving National Cholesterol Education Program low-density lipoprotein cholesterol (LDL-C) goals with titrate-to-goal regimens of simvastatin and fluvastatin. METHODS: This was a multicenter, prospective, randomized, double-blind, parallel-group study enrolling adult patients with type IIa or IIb primary hypercholesterolemia, LDL-C levels <6.0 mmol/L (<232.0 mg/dL), and triglyceride levels <4.5 mmol/L (<398.6 mg/dL), and either CHD or other atherosclerotic disease (the CHD, or high-risk, group), or multiple risk factors for CHD (the MRF, or moderate-risk, group). After a 6-week washout period, patients were randomized to 18 weeks of treatment at an initial dosage of simvastatin 10 mg once daily or fluvastatin 20 mg once daily. At 6- and 12-week titration visits, the dosage in patients who had not acheived the LDL-C goal could be increased to simvastatin 20 mg once daily and then 40 mg once daily, or to fluvastatin 40 mg once daily and then 40 mg twice daily. Lipid profiles were obtained at each titration visit and at the end of treatment. In addition to the comparison between treatments, secondary comparisons were made between the CHD and MRF subgroups within each treatment group. Statistical significance was assessed using analysis of variance. Results: A total of 478 patients were enrolled, 237 in the simvastatin group and 241 in the fluvastatin group. There were no significant between-group differences in patients' characteristics at baseline. At the end of the study, 60.8% (135/222) of patients in the simvastatin group had reached target LDL-C goals, compared with 35.1% (76/216) in the fluvastatin group (P < 0.001). In the simvastatin CHD and MRF subgroups, 49% and 73%, respectively, reached the LDL-C target, compared with 19% and 50% in the corresponding fluvastatin subgroups (P < 0.001). The proportion of patients requiring titration was higher in the fluvastatin group than in the simvastatin group (87.1% and 64.1%, respectively; P = 0.001). The incidence of adverse events was similar between groups. CONCLUSION: In this study, more patients with primary hypercholesterolemia and CHD or multiple risk factors for CHD reached LDL-C goals with simvastatin treatment and required less titration than those who received fluvastatin treatment.