Effects of simvastatin 20 mg/d on serum lipid profiles in Japanese hyperlipidemic patients: A prospective, open-label pilot study

Background:

Hyperlipidemia is a major risk factor for ischemic heart disease. Hydroxymethylglutaryl coenzyme A reductase inhibitors (“statins”) (eg, simvastatin) are considered first-line cholesterol-lowering therapy because they are effective and well tolerated, even at high doses. Based on a literature search, no studies have been published concerning the effects of simvastatin 20 mg/d in Japanese patients who had not previously received lipid-lowering treatment.

Objective:

The aim of this study was to assess the clinical tolerability and effectiveness of simvastatin 20 mg/d in achieving the target lipid concentrations recommended in the 2002 Japan Atherosclerosis Society (JAS) guidelines in Japanese patients with hyperlipidemia.

Methods:

This prospective, open-label pilot study was conducted at Kashiwa Hospital, Jikei University School of Medicine, Kashiwa, Japan. Male and postmenopausal female patients aged ≥18 to 70 years with hyperlipidemia (total cholesterol [TC], ≥220 mg/dL; triglycerides [TG], 150-400 mg/dL) who had not received lipid-lowering medications for at least 6 months before the study were enrolled. Patients received simvastatin 20 mg PO QD for 4 weeks. Effectiveness was assessed using serum concentrations of TC, low-density lipoprotein cholesterol (LDL-C), TG, and lipid peroxide, measured at 0 (baseline) and 4 weeks. Target serum TC and LDL-C concentrations as outlined by the JAS were as follows: category A, TC <240 mg/dL and LDL-C <160 mg/dL; category B1 and B2, TC <220 mg/dL and LDL-C <140 mg/dL; and category C, TC <200 mg/dL and LDL-C <120 mg/dL. A subanalysis of the correlation between baseline high-density lipoprotein cholesterol (HDL-C) and target achievement rates was conducted by baseline HDL-C concentration (<50 or ≥50 mg/dL). Tolerability was assessed using spontaneous reporting of adverse events and laboratory analysis, including liver function tests.

Results:

Twenty-two patients participated in the study (16 women, 6 men; mean [SD] age, 56.0 [8.0] years; mean [SD] body mass index, 23.6 [3.4] kg/m²). Mean serum TC, LDL-C, TG, and lipid peroxide concentrations significantly decreased from baseline (changes, −28.6%, −40.4%, −24.0%, and −14.5%, respectively; P < 0.001, <0.001, <0.001, and <0.01, respectively). The mean HDL-C concentration significantly increased from baseline (change, 7.2%; P < 0.001); the mean increase was significantly greater in patients with baseline HDL-C <50 mg/dL compared with those with baseline HDL-C ≥50 mg/dL (changes, 11.3% vs 4.4%; P < 0.05). Target TC and LDL-C concentrations were achieved in 90.9% of patients. No serious adverse events were observed, and liver enzyme and creatine kinase concentrations did not increase to above-normal values.

Conclusions:

The results of this study suggest that simvastatin 20 mg/d might be useful in the clinical treatment of hyperlipidemia in Japanese patients. The study drug was well tolerated.     

A Highly Bioavailable Omega-3 Free Fatty Acid Formulation Improves the Cardiovascular Risk Profile in High-Risk,Statin-Treated Patients With Residual Hypertriglyceridemia (the ESPRIT Trial)

Background

A novel omega-3 formulation in free fatty acid form (OM3-FFA) has as much as 4-fold greater bioavailability than ethyl ester forms and reduces triglyceride (TG) levels in patients with severe hypertriglyceridemia.

Objective

This study was designed to evaluate the efficacy of adding OM3-FFA (2 or 4 g/d) to statin therapy for lowering non–HDL-C and TG levels in subjects with persistent hypertriglyceridemia and at high risk for cardiovascular disease.

Methods

In this double-blind, parallel-group study, 647 diet-stable patients with fasting TG levels ≥200 mg/dL and <500 mg/dL (treated with a maximally tolerated dose of statin or statin with ezetimibe) and at high risk for cardiovascular disease were randomized to 6 weeks of treatment with capsules of control (olive oil [OO]) 4 g/d, OM3-FFA 2 g/d (plus 2 g/d OO), or OM3-FFA 4 g/d. Assessments included fasting serum levels of lipids and apolipoproteins (apo); plasma concentrations of eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and arachidonic acid; and laboratory safety values and adverse events.

Results

In the 627 subjects in the intention to treat sample, non–HDL-C levels were reduced with OM3-FFA 2 g/d and OM3-FFA 4 g/d (–3.9% and –6.9%, respectively) compared with OO (–0.9%) (both, P < 0.05), as were TG levels (–14.6% and –20.6%, respectively, vs –5.9%; both, P < 0.001). LDL-C levels increased with OM3-FFA 2 g/d (4.6%) compared with OO (1.1%) (P = 0.025) but not with OM3-FFA 4 g/d (1.3%). Total cholesterol and VLDL-C concentrations were reduced compared with OO with both OM3-FFA dosages, and the total cholesterol/HDL-C ratio and apo AI and apo B levels were significantly lowered with OM3-FFA 4 g/d only (all at least P < 0.05). Percent changes from baseline in HDL-C did not differ between OO and either OM3-FFA group. Plasma concentrations of docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid were significantly increased and arachidonic acid was significantly reduced in both OM3-FFA treatment groups compared with the OO responses (all, P < 0.001). Withdrawals related to treatment-emergent adverse events ranged from 0.9% with OO to 3.2% with OM3-FFA 4 g/d.

Conclusions

OM3-FFA was well tolerated and lowered non–HDL-C and TG levels at both 2- and 4-g/d dosages in patients with persistent hypertriglyceridemia taking a statin, with the 4-g/d dosage providing incremental improvements compared with 2 g/d. ClinicalTrials.gov identifier: NCT01408303.     

Metabolic effects of fluvastatin extended release 80 mg and atorvastatin 20 mg in patients with type 2 diabetes mellitus and low serum high-density lipoprotein cholesterol levels: a 4-month, prospective, open-label, randomized, blinded—end point (probe) trial

Background

Diabetic dyslipidemia is characterized by greater triglyceridation of all lipoproteins and low levels of plasma high-density lipoprotein cholesterol (HDL-C). In this condition, the serum level of low-density lipoprotein cholesterol (LDL-C) is only slightly elevated. The central role of decreased serum HDL-C level in diabetic cardiovascular disease has prompted the establishment of a target of ≥50 mg/dL in patients with diabetes mellitus (DM).

Objective

The aim of the study was to assess the effects of once-daily administration of fluvastatin extended release (XL) 80 mg or atorvastatin 20 mg on serum HDL-C levels in patients with type 2 DM and low levels of serum HDL-C.

Methods

This 4-month, prospective, open-label, randomized, blinded—end point (PROBE) trial was conducted at Endocrinology and Diabetology Service, L. Sacco-Polo University Hospital (Milan, Italy). Patients aged 45 to 71 years with type 2 DM receiving standard oral antidiabetic therapy, with serum HDL-C levels <50 mg/dL, and with moderately high serum levels of LDL-C and triglycerides (TG) were enrolled. After 1 month of lifestyle modification and dietary intervention, patients who were still showing a decreased HDL-C level were randomized, using a 1:1 ratio, to receive fluvastatin XL 80-mg tablets or atorvastatin 20-mg tablets, for 3 months. Lipoprotein metabolism was assessed by measuring serum levels of LDL-C, HDL-C, TG, apolipoprotein (apo) A-I (the lipoprotein that carries HDL), and apo B (the lipoprotein that binds very low-density lipoprotein cholesterol, intermediate-density lipoprotein, and LDL on a molar basis). Patients were assessed every 2 weeks for treatment compliance and subjective adverse events. Serum creatine phosphokinase and liver enzymes were assessed before the run-in period, at the start of the trial, and at 1 and 3 months during the study.

Results

One hundred patients were enrolled (50 patients per treatment group; fluvastatin XL group: 33 men, 17 women; mean [SD] age, 58 [12] years; atorvastatin group: 39 men, 11 women; mean [SD] age, 59 [11] years). In the fluvastatin group after 3 months of treatment, mean (SD) LDL-C decreased from 149 (33) to 95 (25) mg/dL (36%; P < 0.01), TG decreased from 437 (287) to 261 (164) mg/dL (40%; P < 0.01), and HDL-C increased from 41 (7) to 46 (10) mg/dL (12%; P < 0.05). In addition, apo A-I increased from 118 (18) to 124 (15) mg/dL (5%; P < 0.05) and apo B decreased from 139 (27) to 97 (19) mg/dL (30%; P < 0.05). In the atorvastatin group, LDL-C decreased from 141 (25) to 84 (23) mg/dL (40%; P < 0.01) and TG decreased from 411 (271) to 221 (87) mg/dL (46%; P < 0.01). Neither HDL-C (41 [7] vs 40 [6] mg/dL; 2%) nor apo A-I (117 [19] vs 114 [19] mg/dL; 3%) changed significantly. However, apo B decreased significantly, from 131 (20) to 92 (17) mg/dL (30%; P < 0.05). Mean changes in HDL-C (+5 [8] vs −1 [2] mg/dL; P < 0.01) and apo A-I (+6 [18] mg/dL vs −3 [21] mg/dL; P < 0.01) were significantly greater in the fluvastatin group than in the atorvastatin group, respectively. However, the decreases in LDL-C (54 [31] vs 57 [32] mg/ dL), TG (177 [219] vs 190 [65] mg/dL), and apo B (42 [26] vs 39 [14] mg/dL) were not significantly different between the fluvastatin and atorvastatin groups, respectively. No severe adverse events were reported.

Conclusions

Fluvastatin XL 80 mg and atorvastatin 20 mg achieved mean serum LDL-C (≤ 100 mg/dL) and apo B target levels (≤ 100 mg/dL) in the majority of this population of patients with type 2 DM, but mean serum HDL-C level was increased significantly only with fluvastatin—16 patients (32%) in the fluvastatin group compared with none in the atorvastatin group achieved HDL-C levels ≥50 mg/dL. The increase in HDL-C in the fluvastatin-treated patients was associated with an increase in apo A-I, suggesting a potential pleiotropic and selective effect in patients with low HDL-C levels.     

Effects of fenofibrate on albuminuria in patients with hypertriglyceridemia and/or hyperuricemia: a multicenter, randomized, double-blind, placebo-controlled, crossover study

Background: A slight increase in albuminuria (urinary albumin excretion [UAE] ≥30 mg/d) is associated with hypertension, type 2 diabetes mellitus, dyslipidemia (high triglyceride [TG] and low high-density lipoprotein cholesterol [HDL-C] concentrations), and hyperuricemia. Although antihypertensive and antidiabetic therapies have been reported to reduce UAE, an association between improvement in dyslipidemia and/or hyperuricemia and a reduction in UAE has not been reported.Objective: The aim of this study was to investigate the efficacy and tolerability of fenofibrate on albuminuria in patients with hypertriglyceridemia and/or hyperuricemia.Methods: Patients with hypertriglyceridemia and/or hyperuricemia were recruited from general clinics and lipid clinics in Japan; they received fenofibrate (300 mg once daily) in this randomized, double-blind, placebo-controlled, crossover study. Patients in group A received fenofibrate for 8 weeks followed by placebo for an additional 8 weeks, whereas those in group B received placebo for 8 weeks followed by fenofibrate for 8 additional weeks. UAE was measured at baseline and at the end of each 8-week period. Blood tests were performed at baseline and every 4 weeks until study end. Each physician who participated in the study was to record adverse events at each study visit.Results: A total of 43 patients entered this study (38 men, 5 women; mean [SE] age, 57.1 [1.4] years; mean [SE] body mass index, 24.3 [0.4] kg/m²). Twenty-one patients (18 men, 3 women) were randomly assigned to group A and 22 (20 men, 2 women) to group B. In group A, serum TG (P<0.001) and apolipoprotein (apo) C2, C3, and E (all P<0.01) concentrations decreased significantly with fenofibrate, and HDL-C and apo A1 and A2 increased significantly (all P<0.001). All of these parameters returned to near-baseline levels after placebo administration. In group B, serum TG, HDL-C, or apo A1, A2, B, C2, C3, and E concentrations did not change significantly with placebo, but TG (P<0.01), apo C3 (P<0.05), and apo E (P<0.05) were significantly decreased with fenofibrate. In addition, HDL-C (P<0.05), apo A1 (P<0.001), and apo A2 (P<0.01) were significantly increased with fenofibrate. Serum concentrations of TG (group A, P<0.001; group B, P<0.001); apo C2 (group A, P<0.01), C3 (group A, P<0.01; group B, P<0.05), and E (group A, P<0.01; group B, P<0.05); and uric acid (group A, P<0.001; group B, P<0.01) were significantly decreased with fenofibrate compared with placebo. HDL-C and apo A1 and A2 were significantly increased with fenofibrate compared with placebo (all P<0.001 in both groups). Fenofibrate treatment was associated with significant reductions in UAE (group A, P<0.05; group B, P<0.01). Spearman rank correlation analysis showed that changes in UAE were associated with changes in apo C2 (ρ = 0.43; P = 0.02) and apo C3 (ρ = 0.49; P = 0.01) concentrations. Multiple regression analysis revealed that a decrease in apo C3 concentration was independently and significantly associated with reductions in albuminuria (ρ = 0.48; P = 0.01). At the end of the study, neither drug-related nor clinical adverse events were evident in any of the patients, except for an increase in serum creatinine concentration above the upper limit of normal (1.40 mg/dL) in 3 patients (14.3%) in group A and 1 patient (4.5%) in group B.Conclusions: In our study population of patients with hypertriglyceridemia and/or hyperuricemia, fenofibrate-induced ameliorations of impaired TG-rich lipoprotein metabolism were associated with reductions in albuminuria.     

Effects of atorvastatin 10 mg and fenofibrate 200 mg on the low-density lipoprotein profile in dyslipidemic patients: A 12-week, multicenter, randomized, open-label, parallel-group study

Background: Elevated plasma low-density lipoprotein cholesterol (LDL-C) concentrations are highly atherogenic, especially the small, dense LDL (sdLDL) species. Fenofibrate has been reported to shift the LDL profile by decreasing the sdLDL subfraction and increasing larger LDL subclasses. Atorvastatin, anantihyperlipidemic agent, has been reported to reduce plasma total cholesterol (TC) and triglyceride (TG) concentrations and thus could modify the LDL profile.Objective: The aim of this study was to compare the effects of fenofi brate and atorvastatin on standard lipid concentrations and the LDL profile.Methods: In this randomized, open-label, parallel-group study, men and women aged 18 to 79 years with type II primary dyslipidemia, defined as LDL-C ≥160 and TG 150 to 400 mg/dL, after a 4- to 6-week washout period while eating an appropriate diet, were randomized to receive either atorvastatin 10 mg once daily or fenofi-brate 200 mg once daily. Plasma lipid concentrations and cholesterol and apolipoprotein (apo) B (reflecting the LDL particle number) in each LDL subfraction prepared by ultracentrifiigation were determined at baseline and after 12 weeks of treatment. Tolerability was assessed using adverse events (AEs) obtained on laboratory analysis and vital sign measurement. Adherence was assessed by counting unused drug supplies.Results: A total of 165 patients (117 men, 48 women; mean [SD] age, 50.1 [10.7] years; mean TC concentration, 289 mg/dL) were randomized to receive atorvastatin (n = 81) or fenofibrate (n = 84). Compared with fenofibrate, atorvastatin was associated with a significantly greater mean (SD) percentage decrease in TC (27.0% [12.3%] vs 16.5% [12.9%]; P < 0.001), calculated LDL-C (35.4% [15.8%] vs 17.3% [17.2%]; P < 0.001), TC/high-density lipoprotein cholesterol (HDL-C) ratio (29.1% [16.3%] vs 22.9% [15.9%]; P = 0.001), and apoB (30.3% [12.7%] vs 19.6% [15.5%]; P < 0.001). Compared with atorvastatin, fenofibrate was associated with a significantly greater decrease in TG (37.2% [25.9%] vs 20.2% [27.3%]; P < 0.001) and a significantly greater increase in HDL-C concentration (10.4% [15.7%] vs 4.6% [12.1%]; P = 0.017). Fibrinogen concentration was significantly different between the 2 groups (P = 0.002); it was decreased with fenofibrate use (4.6% [23.7%]) and was increased with atorvastatin use (5.7% [23.5%]). Atorvastatin did not markedly affect the LDL distribution; it was associated with a homogeneous decrease in cholesterol and apoB concentrations in all subfractions, whereas fenofibrate was associated with a marked movement toward a normalized LDL profile, shifting the sdLDL subfractions toward larger and less atherogenic particles, particularly in those patients with baseline TG ≥200 mg/dL. No serious AEs related to the study treatments were reported. A total of 5 AEs were observed in 8 patients, including: abdominal pain, 3 patients (2 in the atorvastatin group and 1 in the fenofibrate group); abnormal liver function test results, 1 (fenofibrate); increased creatine Phosphokinase activity, 2 (atorvastatin); gastrointestinal disorders, 1 (fenofibrate); and vertigo, 1 (fenofibrate).Conclusion: In these dyslipidemic patients, fenofibrate treatment was associated with an improved LDL subfraction profile beyond reduction in LDL-C, particularly in patients with elevated TG concentration, whereas atorvastatin was associated with equally reduced concentrations of cholesterol and apoB in all LDL subfractions independent of TG concentrations.     

A six-month, multicenter, open-label, noncomparative, prospective, observational study of the efficacy and tolerability of atorvastatin in the primary care setting(estudio del control de las hiperlipidemiasen atención primaria): the cheap study

Background: A close relationship exists between high levels of total cholesterol (TC) (particularly low-density lipoprotein cholesterol [LDL-C]) and low levels of high-density lipoprotein cholesterol (HDL-C), which is associated with an increased risk for arteriosclerosis and cardiovascular disease (CVD). Evidence shows that atorvastatin produces significantly greater reductions in LDL-C and TC than other hydroxymethylglutaryl-coenzyme A reductase inhibitors. However, the results achieved in clinical studies could be different from those found in general clinical practice, where patient follow-up is less thorough and poorer compliance may reduce the effectiveness of the lipid-lowering therapy.Objective: The aim of this study was to assess the effectiveness of atorvastatin in achieving the LDL-C levels recommended by several Spanish scientific societies, as well as its tolerability in standard clinical use.Methods: This 6-month, open-label, noncomparative, prospective, observational study was conducted in 1351 primary care centers in Spain. All patients were aged 18 to 80 years and had primary hypercholesterolemia (TC >200 mg/dL and triglycerides [TG] <200 mg/dL) or combined hyperlipidemia (TC >200 mg/dL and fasting TG 200-400 mg/dL). All patients also had LDL-C levels higher than those established by the Spanish Society of Arteriosclerosis (Sociedad Española de Arteriosclerosis [SEA]) according to baseline cardiovascular risk and previous use of lipid-lowering therapy (for patients with low, moderate, or high cardiovascular risk, the recommended LDL-C goals are ≤175 mg/dL, ≤155 mg/dL, and ≤135 mg/dL, respectively; for patients with CVD, the LDL-C goal is ≤100 mg/dL). None of the patients had creatine kinase activity ≥540 U/L or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥60 U/L. Study visits occurred at months 0, 2, and 6 of treatment. Patients received atorvastatin calcium 10 mg/d for 2 months. The dosage was then doubled to 20 mg/d in patients who did not achieve the SEA LDL-C goal and also in those patients whose primary care physicians (PCPs) deemed this higher dosage necessary; this dosage was continued for at least 4 additional months, to complete at least a 6-month course of treatment. The percentage of patients who achieved their goals was used to measure atorvastatin effectiveness. Percentages of change in LDL-C, TC, TG, and HDL-C from baseline to the final study visit also were used as measures of effectiveness. The incidence of adverse events (AEs) per 10,000 patient-months was used for the primary tolerability analysis. A secondary tolerability analysis was performed in all patients treated with atorvastatin who had some recorded follow-up, regardless of whether the patient met inclusion criteria. Information was obtained from data recorded in the case-report forms.Results: A total of 5317 outpatients (2715 women, 2598 men, 4 sex unknown; mean [SD] age, 58.7 [10.5] years) were enrolled. Among patients receiving known dosages of atorvastatin, 1580 of 4033 (39.2%) and 2378 of 3585 (66.3%) patients met the SEA LDL-C goal after 2 and 6 months of therapy, respectively (P<0.001 for 2 months vs 6 months). Among the patients with low and moderate cardiovascular risk, 85.8% achieved the SEA LDL-C goal compared with 64.4% of high-risk patients (P<0.001). Mean LDL-C decreased by 36.2%. Mean reductions in TC and TG levels were 26.9% and 19.2%, respectively. Mean HDL-C increased 17.0%. One hundred forty-eight patients (2.9%) experienced at least 1 AE and 25 (0.5%) had serious AEs. Eighty-nine patients had 134 AEs considered treatment related. Two of the serious AEs (phlebitis and a severe increase in ALT and AST activity) were considered treatment related. A total of 98.5% and 97.2% of PCPs and patients, respectively, reported excellent or good tolerability with atorvastatin.Conclusions: In this study population, the use of atorvastatin in the primary care setting was associated with high achievement rates of the SEA LDL-C goals and with a substantial decrease in TG levels. In addition, a considerable increase in HDL-C levels occurred. Tolerability with atorvastatin was reported to be excellent or good by most of the patients and PCPs. The incidence of serious AEs was minimal, as reported by both patients and PCPs.     

Effects of policosanol on borderline to mildly elevated serum total cholesterol levels: a prospective, double-blind, placebo-controlled, parallel-group, comparative study

Background

Hypercholesterolemia is a major risk factor for coronary heart disease. Clinical studies have shown that lowering elevated serum cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is beneficial for patients with borderline to mildly elevated serum total cholesterol (TC) levels (5.0-6.0 mmol/L). Policosanol is a cholesterol-lowering drug made from purified sugar cane wax. The therapeutic range of policosanol is 5 to 20 mg/d.

Objective

This study investigated the efficacy and tolerability of policosanol 5 mg/d in patients with borderline to mildly elevated serum TC levels.

Methods

This 14-week, single-center, prospective, double-blind, placebo-controlled, parallel-group, comparative study was conducted in men and women aged 25 to 75 years with a serum TC level ≥4.8 to <6.0 mmol/L. After a 6-week run-in period in which patients were placed on therapeutic lifestyle changes, in particular a cholesterol-lowering diet, patients were randomly assigned to receive policosanol 5-mg tablets or placebo tablets once daily with the evening meal for 8 weeks, and the diet was continued throughout the study. Lipid profile variables, safety indicators, adverse events (AEs), and compliance with study medications were assessed.

Results

One hundred patients (71 women, 29 men; mean [SD] age, 52 [10] years) entered the study after the dietary run-in period. After 8 weeks of treatment, the mean (SD) serum LDL-C level decreased significantly in the policosanol group (P<0.001 vs baseline and placebo) from 3.57 (0.30) mmol/L to 2.86 (0.41) mmol/L (change, −19.9%). Significantly more patients in the policosanol group (42 patients [84%]) achieved a ≥15% decrease in serum LDL-C than in the placebo group (2 patients [4%]) (P<0.001). Also in the policosanol group, the mean (SD) serum TC level decreased significantly, from 5.20 (0.22) mmol/L to 4.56 (0.44) mmol/L (P<0.001 vs baseline and placebo) (change, −12.3%); the mean (SD) triglyceride (TG) level decreased significantly, from 1.59 (0.57) mmol/L to 1.48 (0.57) mmol/L (P<0.01 vs baseline; P<0.05 vs placebo) (change, −6.9%); and the mean (SD) high-density lipoprotein cholesterol (HDL-C) level increased significantly from 1.05 (0.18) mmol/L to 1.16 (0.21) mmol/L (P<0.001 vs baseline and placebo) (change, +10.5%). The percentage changes were significantly different between the policosanol and placebo groups for serum LDL-C, TC, and HDL-C levels (P<0.001, P<0.001, and P<0.05, respectively), but not for TG. In the placebo group, changes in lipid profile variables from baseline were not significant. Policosanol did not significantly impair any safety indicator and was well tolerated. Three patients (3%) (1 patient [2%] in the policosanol group; 2 patients [4%] in the placebo group) withdrew from the trial, none because of AEs. Two patients (1 patient [2%] each in the policosanol and placebo groups) withdrew from the study because of an unwillingness to return for follow-up; 1 patient (2%) in the placebo group had a change of address and could not be followed up. Overall, 4 patients (4%) (1 patient [2%] in the policosanol group; 3 [6%], placebo) reported AEs; all were mild. Of the patients who received placebo and reported AEs, all 3 (6%) experienced heartburn, and 1 (2%) also experienced dry skin, while the policosanol-treated patient (2%) who reported an AE experienced headache.

Conclusions

In this study of patients with borderline to mildly elevated serum TC levels, based on the criterion that ≥70% of policosanol-treated patients reached the LDL-C goal of a decrease ≥15% from baseline whenever this proportion was different with respect to placebo, 8 weeks of treatment with policosanol 5 mg/d was effective. The decreased LDL-C, TC, and TG levels, increased HDL-C level, and good tolerability found with this treatment support its use in such patients.     

Increased serum triglyceride clearance and elevated high-density lipoprotein 2 and 3 cholesterol during treatment of primary hypertriglyceridemia with bezafibrate

Background

Hypertriglyceridemia accompanied by low levels of high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. High-density lipoprotein 2 (HDL₂) and 3 (HDL₃) are believed to suppress the progress of atherosclerosis through reverse cholesterol transport. As a result, peripheral tissues can be protected against excessive accumulation of cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C, results are not standardized regarding increases of HDL₃ and HDL₂ subfractions.

Objective

This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K₂) and HDL₂ and HDL₃ cholesterol (HDL₂-C and HDL₃-C, respectively) levels in patients with primary hypertriglyceridemia (serum TG ≥150 mg/dL).

Methods

Outpatients with primary hypertriglyceridemia were enrolled in this 8-week study conducted at the Third Department of Internal Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8 weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL₂-C, and HDL₃-C were measured. A fat emulsion tolerance test to assess K₂ and measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic triglyceride lipase (HTGL) activity in postheparin plasma were performed before bezafibrate administration and after the course of treatment.

Results

Sixteen patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30-69 years]; mean [SD] body mass index, 23 [2] kg/m²) entered the study. The following findings were observed in male and female patients after 8 weeks of treatment. A statistically significant reduction was observed in mean serum TG level (P<0.01). Significant increases were seen in HDL-C, HDL₂-C, and HDL₃-C (all P<0.01), K₂ (P<0.01), and in plasma LPL mass (P<0.01) and LPL activity (P<0.05). TC level and HTGL activity did not change significantly. No adverse effects related to the use of bezafibrate were documented.

Conclusions

In this study, bezafibrate treatment resulted in significant decreases in serum TG level and significant increases in HDL₂-C and HDL₃-C levels and plasma LPL mass and activity. We hypothesize that bezafibrate may increase HDL₃-C by promoting TG-rich lipoprotein catabolism and may increase HDL₂-C by promoting the conversion of HDL₃ to HDL₂.     

Comparison of the Lipid-Lowering Effects of Pitavastatin 4 mg Versus Pravastatin 40 mg in Adults With Primary Hyperlipidemia or Mixed (Combined) Dyslipidemia: A Phase IV,Prospective, US,Multicenter, Randomized,Double-blind,Superiority Trial

Purpose

Results from a Phase III, European, noninferiority trial in elderly (age ≥65 years) patients with primary hyperlipidemia or mixed (combined) dyslipidemia demonstrated significantly greater reductions in LDL-C for pitavastatin versus pravastatin across 3 pair-wise dose comparisons (1 mg vs 10 mg, 2 mg vs 20 mg, and 4 mg vs 40 mg, respectively). The present study investigated whether pitavastatin 4 mg is superior to pravastatin 40 mg in LDL-C reduction in adults (18–80 years old) with primary hyperlipidemia or mixed (combined) dyslipidemia.

Methods

This was a Phase IV, multicenter, randomized, double-blind, double-dummy, active-control superiority study conducted in the United States. Patients with baseline LDL-C levels of 130 to 220 mg/dL (inclusive) and triglyceride levels ≤400 mg/dL after a 6-week washout/dietary stabilization period were randomized to 12 weeks of once-daily treatment with either pitavastatin 4 mg or pravastatin 40 mg.

Findings

A total of 328 subjects (164 per treatment arm) were randomized (mean age, 57.9 years [76% were aged <65 years]; 49.4% women; mean body mass index, 30.2 kg/m²) to treatment. The median percent change in LDL-C from baseline to the week 12 endpoint was –38.1% for pitavastatin 4 mg and –26.4% for pravastatin 40 mg; the difference in median percent change between treatments was –12.5% (P < 0.001). Differences between treatments in median percent reductions from baseline for apolipoprotein B, total cholesterol, and non–HDL-C were also significant in favor of pitavastatin (P < 0.001). Both treatments significantly (P < 0.001) increased HDL-C and decreased triglycerides, but the differences between treatments were not statistically significant. The overall rate of treatment-emergent adverse events was 47.6% (78 of 164) for pitavastatin and 44.5% (73 of 164) for pravastatin. Myalgia was reported by 3 patients (1.8%) in the pitavastatin group and by 4 patients (2.4%) in the pravastatin group. There were no reports of myositis or rhabdomyolysis.

Implications

Pitavastatin 4 mg demonstrated superior LDL-C reductions compared with pravastatin 40 mg after 12 weeks of therapy in adults with primary hyperlipidemia or mixed (combined) dyslipidemia. There were no new safety findings in the trial. Clinical Trials.gov identifier: NCT01256476.     

Efficacy and Tolerability of Pitavastatin Versus Pitavastatin/Fenofibrate in High-risk Korean Patients with Mixed Dyslipidemia: A Multicenter,Randomized, Double-blinded,Parallel, Therapeutic Confirmatory Clinical Trial

PurposeDyslipidemia is an important risk factor for cardiovascular disease (CVD). Statins are known to effectively reduce not only low-density lipoprotein cholesterol (LDL-C) level but also death and nonfatal myocardial infarction due to coronary heart disease. The risk for CVD from atherogenic dyslipidemia persists when elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) levels are not controlled with statin therapy. Therefore, statin/fenofibrate combination therapy is more effective in reducing CVD risk. Here, we assessed the efficacy and tolerability of pitavastatin/fenofibrate combination therapy in patients with mixed dyslipidemia and a high risk for CVD.MethodsThis multicenter, randomized, double-blind, parallel-group, therapeutic-confirmatory clinical trial evaluated the efficacy and tolerability of fixed-dose combination therapy with pitavastatin/fenofibrate 2/160 mg in Korean patients with a high risk for CVD and a controlled LDL-C level (<100 mg/dL) and a TG level of 150–500 mg/dL after a run-in period with pitavastatin 2 mg alone. In the 8-week main study, 347 eligible patients were randomly assigned to receive pitavastatin 2 mg with or without fenofibrate 160 mg after a run-in period. In the extension study, patients with controlled LDL-C and non–HDL-C (<130 mg/dL) levels were included after the completion of the main study. All participants in the extension study received the pitavastatin/fenofibrate combination therapy for 16 weeks for the assessment of the tolerability of long-term treatment.FindingsThe difference in the mean percentage change in non–HDL-C from baseline to week 8 between the combination therapy and monotherapy groups was −12.45% (95% CI, −17.18 to −7.72), and the combination therapy was associated with a greater reduction in non-HDL-C. The changes in lipid profile, including apolipoproteins, fibrinogen, and high-sensitivity C-reactive protein from baseline to weeks 4 and 8 were statistically significant with combination therapy compared to monotherapy at all time points. Furthermore, the rates of achievement of non–HDL-C and apolipoprotein B targets at week 8 in the combination therapy and monotherapy groups were 88.30% versus 77.98% (P = 0.0110) and 78.94% versus 68.45% (P = 0.0021), respectively. The combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy.ImplicationsIn these Korean patients with mixed dyslipidemia and a high risk for CVD, combination therapy with pitavastatin/fenofibrate was associated with a greater reduction in non–HDL-C compared with that with pitavastatin monotherapy, and a significantly improvement in other lipid levels. Moreover, the combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. Therefore, pitavastatin/fenofibrate combination therapy could be effective and well tolerated in patients with mixed dyslipidemia. ClinicalTrials.gov identifier: NCT03618797.     

Timing clinical events in the treatment of pancreatitis and hypertriglyceridemia with therapeutic plasmapheresis

Background

Hyperlipidemic pancreatitis (HP) is caused by severe hypertriglyceridemia (SHTG). Evidence of SHTG refractoriness to standard medical treatment but not to therapeutic apheresis has increased in the last years.

Methods

Described is the timing of clinical events and the sequence of therapeutic plasma-exchange (TPE) procedures to treat pancreatitis due to SHTG in a male patient, Caucasian, aged 49 years, referred to emergency for severe epigastric pain. There was no history of alcohol consumption, a pre-existing mild hyperlipidemia was treated with diet alone, and biliary imaging was normal. Physical examination revealed epigastric tenderness. Laboratory investigation revealed marked hypertriglyceridemia (11,355 mg/dL; range: 30–150), and hypercholesterolemia (941 mg/dL; range: 80–200). Serum amylase (Amy) and lipase (Lip) were increased: 160 UI/L (range: 20–100) and 175 UI/L (range: 13–60), respectively. A computerized tomography (CT) scan of the abdomen revealed a picture compatible with acute pancreatic phlogosis. It was diagnosed as “acute secondary pancreatitis (AP) and SHTG”.

Results

The patient was successfully submitted to three sessions of TPE in emergency. He was released from hospital after 13 days of hospitalization. The levels of lipids and lipoproteins in his plasma were as follows: triglycerides (TG) 185 mg/dL; total cholesterol (TC) 179 mg/dL; HDL-cholesterol (HDLC) 22 mg/dL; LDL-cholesterol (LDLC) 120 mg/dL.

Conclusions

The decision to submit the patient with clinical evidence of HP caused by SHTG to apheresis was correct. The improvement in the clinical picture was fast and the recovery was complete.     

Atherogenic lipid profile and high sensitive C-reactive protein in patients with rheumatoid arthritis

Objectives

The objective of this study was to investigate the lipid profile and high sensitive C-reactive protein (hs-CRP) levels in rheumatoid arthritis (RA) patients, and compare them with healthy controls, and also compare the different patterns of these parameters during active RA between male and female patients.

Design and methods

We studied 60 RA patients and 65 controls matched by age and sex. All cases were selected from the Rheumatology Department of a tertiary care hospital, Delhi, India and fulfilled the 1987 American College of Rheumatology revised criteria for RA.

Results

We found that male RA patients had significantly higher levels of hs-CRP (p < 0.001), low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) (p < 0.001), total cholesterol (TC)/HDL-C (p < 0.05), and lower level of HDL-C (p < 0.01), than male controls. The mean levels of HDL-C and TC were high (p < 0.05), and LDL-C, LDL-C/HDL-C (p < 0.01), and hs-CRP (p < 0.001) were low in healthy females as compared to female RA patients. Between RA patients, females had significantly high level of HDL-C (p < 0.001), and low levels of TC/HDL-C and LDL-C/HDL-C (p < 0.001) as compared to RA males. Mean levels of TC and HDL-C were higher in healthy females (p < 0.05) and triglyceride (TG) was lower (p < 0.05) than in healthy males.

Conclusions

Results demonstrate that the RA patients have high levels of inflammatory marker hs-CRP and altered lipid profile, and these are affected by the gender of the RA patients. Lipid levels should be monitored and managed in patients with RA to minimize the long-term risk of cardiovascular disease.     

甘糖酯与非诺贝特调脂疗效比较

目的 比较甘糖酯与非诺贝特的调脂疗效。方法84例原发性高脂血症患者随机分为2组：甘糖酯组43例，口服甘糖酯100mg，每日3次；非诺贝特组41例，口服非诺贝特100mg，每日3次，均以8周为一疗程。比较治疗前后血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL—C)水平的变化。结果 甘糖酯组与非诺贝特组降TC总有效率分别为89％与84％；降低TG总有效率分别为91％与93％；升高HDL-C总有效率分别为86％与84％，但两组间比较差异无统计学意义(P＞0．05)。结论 甘糖酯与非诺贝特调脂效果均显著，两者疗效相仿。     

Effects of simvastatin on blood pressure in hypercholesterolemic patients: An open-label study in patients with hypertension or normotension

Background

Simvastatin has been reported to improve endotheliumdependent vascular relaxation in patients with hypercholesterolemia. The consequent decrease in arterial stiffness might be associated with a decrease in blood pressure (BP).

Objective

The aim of this study was to determine whether simvastatin 20 and 40 mg/d have an effect on systolic and diastolic blood pressure (SBP and DBP, respectively) in patients with hypercholesterolemia, and, if so, whether the effect is dose dependent and/or is related to the changes in the serum lipid profile.

Methods

This 6-month, open-label study was conducted at the Lipid Clinics of the Department of Internal Medicine, University of Milan, Maggiore Hospital IRCCS, and of the Department of Internal Medicine 1, G. Salvini Hospital, Garbagnate Milanese (Milan, Italy). Patients aged 18 to 80 years with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet for >2 months before the study were enrolled. Patients at high risk for cardiovascular disease (CVD), according to the National Cholesterol Education Program Adult Treatment Panel II guidelines, were given simvastatin 20 mg (tablet) QD for 3 months, and those at low risk for CVD continued with diet only for 3 months (controls). Efficacy variables included body weight, SBP, DBP, and serum lipid levels (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high density lipoprotein cholesterol [HDL-C], and triglycerides [TG]). At 3 months, patients in the simvastatin + diet group who reached their therapeutic goal continued to receive simvastatin 20 mg/d for 3 additional months. In simvastatintreated patients who were normotensive at baseline or who became normotensive at 3 months but who did not reach the therapeutic goal, the simvastatin dosage was increased to 40 mg/d. Patients in both groups who remained hypertensive at 3 months were switched to hypotensive therapy. In the diet-only group, patients who were formerly normotensive or who became normotensive at 3 months but who did not reach their therapeutic goal continued with diet only or started lipid-lowering therapy. All other patients in the diet-only group continued to be treated with diet only, for 3 additional months. Efficacy variables were measured again at 6 months. Tolerability of simvastatin was assessed at each visit using patient interview and measurement of serum aminotransferase and creatine phosphokinase levels.

Results

The study population comprised 222 patients (132 women, 90 men; mean [SEM] age, 53.9 [0.95] years [range, 23-76 years]); 115 high-risk patients (57 with untreated stage 1 hypertension) were assigned to the simvastatin + diet group, and 107 low-risk patients (29 with untreated stage 1 hypertension) were assigned to the diet-only group. In the simvastatin group, after 3 months of therapy, mean SBP was decreased by 3.9 (1.49) mm Hg (change, −2.9%), mean DBP decreased by 3.0 (0.87) mm Hg (change, −3.7%), mean TC decreased by 90.6 (3.98) mg/dL (change, −27.0%), mean LDL-C decreased by 88.9 (3.88) mg/dL (change, −35.6%), and mean TG decreased by 26.3 (7.34) mg/dL (change, −15.8%) (all, P < 0.001). Mean HDL-C increased by 3.6 (1.16) mg/dL (change, 6.9%; P < 0.001). The BP-lowering effect was found only in patients with hypertension at baseline (n = 57); in these patients, mean SBP decreased by 7.2 (2.44) mm Hg (change, −4.8%; P < 0.005 vs baseline) and DBP decreased by 4.8 (1.29) mm Hg (change, −5.6%; P < 0.001 vs baseline). Also in the simvastatin group, 26 patients (22.6%) achieved their target SBP/DBP. In patients with normotension at baseline (n = 58), neither SBP nor DBP was changed significantly (changes, −0.8 [1.65] and −1.4 [1.15] mm Hg, respectively [−0.6% and −1.8%, respectively]). The changes in serum lipid levels were similar between hypertensive and normotensive patients in the simvastatin group. Forty-one patients (18 hypertensive and 23 normotensive at baseline) were treated with simvastatin 40 mg/d plus diet between months 3 and 6. At 6 months, no further significant decrease was observed in mean BP. In contrast, the expected dose-dependent response was observed for TC and LDL-C levels. In the diet-only group, no significant changes occurred in BP or serum lipid levels. Changes in BP, TC, LDL-C, TG, and HDL-C were significantly greater in the simvastatin + diet group than in the diet-only group (all, P < 0.001). Body weight did not change significantly in either group.

Conclusions

In this group of patients with hypercholesterolemia, the starting dosage of simvastatin (20 mg/d) was associated with reductions in SBP and DBP within 3 months of treatment in patients with hypertension, and this effect was independent of the lipid-lowering properties of the drug. Although the decrease in BP was modest, it is likely clinically relevant. Further studies on this topic are advisable.     

Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: A 12-week,multicenter, double-blind,randomized, parallel-group study

Background: Coadministration of statin and fenofibrate monotherapies is frequently used to treat patients with dyslipidemia; however, a fixed-dose combination (FDC) tablet is not currently marketed.Objective: This study evaluates a new FDC tablet of atorvastatin 40 mg and fenofibrate 100 mg.Methods: This was a 12-week, multicenter, doubleblind, randomized, parallel-group Phase IIb study. Adults with dyslipidemia (non?HDL-C >130 mg/dL and triglycerides [TG] ≥150 but ≤500 mg/dL) were randomly assigned in a 1:1:1 ratio to receive the FDC, atorvastatin 40 mg, or fenofibrate 145 mg for 12 weeks. Study medication was taken once daily in the evening, without regard to meals. Patients attended follow-up visits after 4, 8, and 12 weeks of the double-blind treatment. The primary efficacy end points were the mean percentage changes from baseline to the final visit (week 12) in non?HDL-C, HDL-C, and TG. Secondary variables were LDL-C, VLDL-C particle concentration, total cholesterol, apolipoprotein B, lipoprotein (a), high-sensitivity C-reactive protein, fibrinogen, homocysteine, creatinine, myeloperoxidase, and lipoproteinassociated phospholipase A2. Tolerability was assessed by adverse events, laboratory parameters, vital signs, physical examinations, and ECGs.Results: Patients (n = 220) were aged 26 to 87 years; 115 (52.3%) were men and 105 (47.7%) were women; 189 (85.9%) were white, 17 (7.7%) were black, and 15 (6.8%) were Hispanic or Latino; and mean (SD) weight was 200.5 (40.85) lb (range, 103.5–367.4 lb). Previous treatments were statins (25.9% [57/220]), fibrates (1.8% [4/220]), and dietary supplements (25.5% [56/220]); 57.7% (127/220) of patients were treatment naive. Use of the FDC was associated with an improvement in non?HDL-C (?44.8%) that was significantly greater than with fenofibrate monotherapy (?16.1%; P < 0.001) but was not significantly different from that with atorvastatin monotherapy (?40.2%; P = NS). HDL-C increased significantly more in the FDC group (19.7%) than with atorvastatin (6.5%; P < 0.001) but was not significantly different from fenofibrate (18.2%; P = NS). TG lowering in the FDC group (?49.1%) was significantly greater than with both atorvastatin (?28.9%; P < 0.001) and fenofibrate (?27.8%; P = 0.001). LDL-C lowering in the FDC group (?42.3%) was significantly greater than with fenofibrate (?13.9%; P < 0.001) but not significantly different from atorvastatin (?43.1%; P = NS). The FDC had either comparable or significantly greater improvements in other lipid variables and multiple secondary variables. The FDC was generally well tolerated; the tolerability profile was consistent with those of atorvastatin and fenofibrate monotherapies. Treatment-emergent adverse events (ie, those occurring after the first dose of study medication) were recorded in 43 of 73 patients (58.9%) for the FDC, 49 of 74 (66.2%) for atorvastatin, and 48 of 73 (65.8%) for fenofibrate.Conclusions: In this 12-week study, patients with dyslipidemia treated with the 40/100-mg atorvastatin/ fenofibrate FDC had a significantly greater reduction in TG than those treated with atorvastatin 40 mg or higher-dose fenofibrate 145 mg. Treatment with the FDC was also associated with a significantly greater reduction in non?HDL-C compared with fenofibrate alone and a greater increase in HDL-C compared with atorvastatin alone. All treatments were generally well tolerated.     

Fenofibrate in the treatment of dyslipidemia: a review of the data as they relate to the new suprabioavailable tablet formulation

BACKGROUND: The fibric acid derivative fenofibrate is indicated as an adjunct to dietary modification in adults with primary hypercholesterolemia or mixed dyslipidemia (types IIa and IIb hyperlipidemia, Fredrickson classification) to reduce levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and apolipoprotein (apo) B, and to increase levels of high-density lipoprotein cholesterol (HDL-C) and apo A. It is also indicated as adjunctive therapy to diet for the treatment of hypertriglyceridemia (types IV and V hyperlipidemia). Initially approved in the United States in a micronized capsule formulation, fenofibrate is now available in a new "suprabioavailable" tablet formulation that has increased bioavailability, achieving equivalent plasma concentrations at lower doses. The 67- and 200-mg micronized capsules can be considered equivalent to the 54- and 160-mg suprabioavailable tablets, respectively. OBJECTIVE: This paper reviews the pharmacologic properties, clinical usefulness, and safety profile of fenofibrate in the management of dyslipidemias. METHODS: Recent studies, abstracts, reviews, and consensus statements published in the English-language literature were identified through searches of MEDLINE (1966-January 2002), International Pharmaceutical Abstracts (1970-January 2002), and PharmaProjects (1990-January 2002) using the search terms fenofibrate, fibrates, hyperlipidemia, hypertriglyceridemia, and dyslipidemia. RESULTS: Fenofibrate is well absorbed after oral administration, with peak plasma levels attained in 6 to 8 hours. The absolute bioavailability of fenofibrate cannot be determined due to its being virtually insoluble in aqueous media suitable for injection; however, after oral administration of a single dose of radiolabeled fenofibrate, approximately 60% of the dose appeared in urine, primarily as fenofibric acid and its glucuronated conjugate, and approximately 25% was excreted in the feces. The apparent volume of distribution is 0.89 L/kg in healthy volunteers, and protein binding is approximately 99% in healthy and hyperlipidemic patients. Neither fenofibrate nor fenofibric acid appears to undergo significant oxidative metabolism in vivo. Fenofibric acid has a half-life of 20 hours. Fenofibrate is effective in lowering TG levels and increasing HDL-C levels. Its LDL-C-lowering effect is greater than that of gemfibrozil. Adverse effects of fenofibrate appear to be similar to those of other fibrates, including gastrointestinal symptoms, cholelithiasis, hepatitis, myositis, and rash. Fenofibrate therapy has been associated with increases in serum aminotransferase levels, and clinical monitoring of these markers of liver function should be performed regularly. CONCLUSIONS: Fenofibrate is effective in reducing levels of TG, TC, and LDL-C, and increasing levels of HDL-C in patients with dyslipidemias. Its efficacy and tolerability in the treatment of hypertriglyceridemia and combined hyperlipidemia have been demonstrated in numerous clinical trials. Its use is accompanied by a low incidence of adverse effects and laboratory abnormalities. Fenofibrate protects against coronary heart disease not only through its effects on lipid parameters but also by producing alterations in LDL structure and, possibly, alterations in the various hemostatic parameters. Its uricosuric property may prove to be a useful adjunctive attribute.     

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 Randomized,Double-Blind Study of Fenofibric Acid Plus Rosuvastatin Compared With Rosuvastatin Alone in Stage 3 Chronic Kidney Disease

Background

Patients with chronic kidney disease (CKD) often have mixed dyslipidemia and high cardiovascular disease risk. Although statins reduce LDL-C, adding a fibrate may further improve lipid parameters.

Objective

This multicenter, randomized study evaluated the short-term efficacy and safety profile of fenofibric acid (FA) + rosuvastatin (R) combination therapy for improving lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. The study also assessed estimated glomerular filtration rate after study drug washout.

Methods

Patients received FA 45 mg + R (5 mg for 8 weeks, then 10 mg for 8 additional weeks) or R monotherapy (5 mg for 8 weeks, then 10 mg for 8 additional weeks), followed by an 8-week washout period. Primary and secondary end points were percent changes in triglycerides and HDL-C, respectively, from baseline to week 8.

Results

FA 45 mg + R 5 mg, compared with R 5 mg, resulted in significant improvements in triglycerides (median % changes: week 8, −38.0% vs −22.4%, P < 0.001; week 16, −42.6% vs −29.7%, P < 0.001) and HDL-C (mean % changes: week 8, 16.9% vs 7.8%, P < 0.001; week 16, 17.3% vs 8.9%, P < 0.001). Adverse event rates were similar between groups (70.7% with FA + R vs 68.6% with R). Mean serum creatinine level at baseline was 1.36 mg/dL in the FA + R group and 1.38 mg/dL in the R group. The final treatment serum creatinine value, defined as the last nonmissing postbaseline value collected within 30 days after the last dose of study drug, was 1.52 mg/dL with FA + R (vs 1.41 mg/dL with R; P < 0.001), which then decreased to 1.39 mg/dL after the 8-week washout (vs 1.42 mg/dL with R).

Conclusions

The data suggest that, after 16 weeks of therapy, FA + R has an acceptable safety profile and improved TG and HDL-C efficacy versus R. FA + R combination therapy may thus further improve lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. ClinicalTrials.gov identifier: NCT00680017.     

Efficacy and Safety of Adding Omega-3 Fatty Acids in Statin-treated Patients with Residual Hypertriglyceridemia: ROMANTIC (Rosuvastatin-OMAcor iN residual hyperTrIglyCeridemia), a Randomized,Double-blind,and Placebo-controlled Trial

Purpose

The purpose of this study was to examine the efficacy and safety of adding ω-3 fatty acids to rosuvastatin in patients with residual hypertriglyceridemia despite statin treatment.

非诺贝特治疗高脂血症40例疗效观察

目的：观察非诺贝特对高脂血症的疗效。方法：对４０例高脂血症患者使用非诺贝特，每日３００ｍｇ，疗程６个月；治疗前后检测血清总胆固醇（ＴＣ）、甘油三酯（ＴＧ）、低密度脂蛋白胆固醇（ＬＤＬＣ）、高密度脂蛋白胆固醇（ＨＤＬＣ）和载脂蛋白Ａ１（ａｐｏＡ１）、载脂蛋白Ｂ（ａｐｏＢ）等。结果：ＴＧ平均降低了４５．２％，ＴＣ平均降低了２０．５％，ＨＤＬＣ平均上升了１５．４％，ＬＤＬＣ平均降低了２５．５％，ａｐｏＡ１平均上升了２．０％，ａｐｏＢ平均下降了３０．０％。结论：非诺贝特具有降低ＴＧ、ＴＣ、ＬＤＬＣ、ａｐｏＢ和升高ＨＤＬＣ、ａｐｏＡ１作用，从而可减少冠状动脉粥样硬化性心脏病的发病率和病死率