A retrospective meta-analysis of the efficacy and tolerability of fenofibrate 300 mg/d on high-density lipoprotein cholesterol levels in randomized, double-blind, comparative studies conducted in Japan

Background

Low levels of plasma high-density lipoprotein cholesterol (HDL-C) represent an important risk factor for coronary heart disease (CHD). Increasing HDL-C by 1 mg/dL decreases the incidence of CHD by 2% to 3%. Fenofibrate increases HDL-C by ∼23%, to ≥40 mg/dL, and may be effective in preventing CHD.

Objective

The aim of this study was to assess the effects of fenofibrate on HDL-C in patients treated for 12 weeks in 3 randomized, double-blind, comparative studies conducted in Japan. Changes in total cholesterol (TC) and triglycerides (TG), effects on HDL-C and apolipoprotein (apo) A-I and A-II by TG level, and effects on serum lipid levels by type of hyperlipidemia were the secondary end points.

Methods

Changes in HDL-C levels, as well as TC and TG levels, were analyzed in patients who received fenofibrate 300 mg/d for 12 weeks. Patients aged 20 to 80 years with mean TC ≥220 mg/dL (hypercholesterolemia), TG ≥150 mg/dL (hypertriglyceridemia), or both (combined hyperlipidemia) were considered assessable.

Results

In this retrospective meta-analysis conducted at Grelan Pharmaceutical Co. Ltd. (Tokyo, Japan), data from 263 patients (137 women, 126 men; mean [SD] age, 56.0 [10.8] years; range, 25-79 years) were included. The mean (SD) HDL-C level increased significantly, from 46.1 (0.9) mg/dL to 55.9 (1.0) mg/dL after 12 weeks of treatment with fenofibrate (P<0.001). Serum TC and TG decreased significantly (both P<0.001). HDL-C elevation was greater in patients with TG ≥150 mg/dL than in patients with TG<150 mg/dL, although apo A-I and A-II changes were the same in both groups. HDL-C increased in every type of hyperlipidemia, 14.9% in hypercholesterolemia, 22.0% in hypertriglyceridemia, and 33.5% in combined hyperlipidemia. Baseline HDL-C levels were <40 mg/dL in 93 patients (group 1) and ≥40 mg/dL in 170 patients (group 2). Mean HDL-C levels increased significantly in both groups during the treatment period, from 32.6 (0.6) mg/dL to 42.6 (1.0) mg/dL in group 1 and from 53.5 (0.9) mg/dL to 63.1 (1.1) mg/dL in group 2 (both P<0.001). One patient (0.3%) of the 331 included in the tolerability analysis experienced a serious adverse effect (jaundice).

Conclusion

In this study of patients with hypercholesterolemia, hypertriglyceridemia, or combined hyperlipidemia, 12-week treatment with fenofibrate 300 mg/d was effective and generally well tolerated, with the possible exception of transient changes in aminotransferases. HDL-C was increased in all patients to ∼40 mg/dL, the target level.     

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.     

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 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.     

Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia.

BACKGROUND: Simvastatin 40 to 80 mg/d has been found to increase high-density lipoprotein cholesterol (HDL-C) levels significantly more than atorvastatin at equipotent doses (ie, 20-80 mg/d). Data on the effects of lower doses of the 2 drugs on HDL-C levels are conflicting. OBJECTIVE: The purpose of this study was to investigate the effects of simvastatin 20 mg/d and atorvastatin 10 mg/d on HDL-C levels in patients with hypercholesterolemia. METHODS: Patients with primary hypercholesterolemia (total cholesterol [TC] >250 mg/dL) who were not taking any lipid-lowering agents and who were following a low-fat diet were randomized to receive 1 of 2 treatments: simvastatin 20 mg/d or atorvastatin 10 mg/d. Serum TC, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and HDL-C levels were measured using standard methods after 2 months of therapy. In a secondary analysis, lipids and lipoprotein cholesterol were measured after 1 year in patients who continued treatment. RESULTS: Of the 240 patients enrolled (108 men and 132 women; age range, 23-77 years, mean [SEM] 56.7 [0.69]), 235 completed the study. After 2 months of therapy, TC, LDL-C, and serum TG levels decreased significantly versus baseline in both groups (P < 0.001), with no significant differences between treatment groups. HDL-C levels increased by 9.0% (P < 0.001 vs baseline) in the simvastatin group and by 4.3% (P < 0.02) in the atorvastatin group. The difference between the 2 groups in the percentage increase in HDL-C was statistically significant (P < 0.05). In 113 patients who continued treatment, HDL-C levels at 1 year were still significantly higher than baseline levels in the simvastatin group (6.3%, P = 0.034), but not in the atorvastatin group (2.8%, P = 0.587). CONCLUSIONS: The findings from this study suggest that the HDL-C-increasing effect of simvastatin 20 mg is significantly greater than that of atorvastatin 10 mg. Since increasing HDL-C levels is thought to lower the risk for atherosclerosis and coronary heart disease, these results warrant further investigation.     

Effects of combination treatment with policosanol and omega-3 fatty acids on platelet aggregation: A randomized, double-blind clinical study

Background:

Policosanol is a mixture of long-chain primary aliphatic alcoholspurified from sugar cane wax that has cholesterol lowering and antiplatelet effects. Omega-3 fatty acids (FA) have triglyceride lowering and antiplatelet effects. Combination treatment with policosanol and omega-3 FA (Ω23FA) has been associated with significant inhibition of platelet aggregation in rabbits compared with either drug alone.

Objective:

The aim of this study was to investigate the effects of combination treatment with Ω3FA (1 g/d) and policosanol (Ω3FA+Poli) compared with Ω3FA (1 g/d) plus placebo (Ω3FA+Pla) on platelet aggregation in human patients with hypercholesterolemia.

Methods:

This randomized, double-blind, clinical study at the Surgical Medical Research Center (Havana City, Cuba) recruited outpatients from lipid clinics, with some atherosclerotic risk factors. Outpatients of both sexes aged 20 to 75 years with serum total cholesterol (TC) levels ≥5 and <6 mmol/L were eligible to enroll. They were included in the study at the end of a 4-week diet stabilization period if their platelet aggregation to arachidonic acid (AA) was ≥50% and serum TC level remained ≥5 mmol/L. Patients were then evenly randomized to receive Ω3FA (1 g/d) + placebo or Ω3FA (1 g/d) + policosanol (10 mg/d) to be taken PO with the evening meal for 21 days. Treatment was assigned according to a randomization code using balanced blocks and a 1:1 allocation ratio. Inhibition of platelet aggregation to AA was the primary efficacy variable, while effects on platelet aggregation to collagen and epinephrine and on lipid profile were secondary variables. Drug compliance and adverse events (AEs) were monitored. Tolerability was assessed using physical examinations and laboratory test results.

Results:

Sixty-four subjects were initially enrolled. Fifty-four patients (30 women, 24 men; mean [SD] age, 58.4 [12] years, [range, 40-70 years]) met the inclusion criteria and were randomized to treatment; 2 groups of 27. After 21 days, platelet aggregation to AA was significantly inhibited in the 2 groups. Ω3FA+Poli inhibited platelet aggregation to all agonists by ≥20%. Platelet aggregation to AA 1.0 and 1.5 mM was inhibited with combination treatment (39.6% and 33.9%, respectively; both P < 0.001 vs baseline; P < 0.001 and P < 0.01, respectively, vs Ω3FA+Pla) and with Ω3FA+Pla (11.0% and 13.3%; both, P < 0.001). Combination treatment was more effective in inhibiting platelet aggregation to AA 1.0 and 1.5 mM in 28.6% (P < 0.001) and 20.6% (P < 0.01), respectively. Platelet aggregation to collagen 1 μg/mL was significantly inhibited with combination treatment and with Ω3FA+Pla compared with baseline (43.2% and 15.1%, respectively; both, P < 0.001), but the effects of combination treatment were significantly greater (P < 0.01). Platelet aggregation to epinephrine 0.1 mM was inhibited with Ω3FA+Poli and Ω3FA+Pla (34.8% and 20.1%; both, P < 0.001), with similar results for both groups. Bleeding time did not change significantly for either group and Ω3FA+Pla did not significantly change the lipid profile. Combination treatment did significantly reduce levels of low-density lipoprotein cholesterol (LDL-C) (17.4%; P < 0.001 vs baseline, P < 0.05 vs Ω3FA+Pla) and TC (10.1%; P < 0.001 vs baseline, P < 0.05 vs Ω3FA+Pla), increase high-density lipoprotein cholesterol (HDL-C) levels (18.0%; P < 0.001 vs baseline), but did not significantly change triglyceride levels. Three patients (2 from the Ω3FA+Poli group and 1 from the Ω3FA+Pla group) withdrew from the trial, though none were due to AEs. Two patients receiving combination treatment reported mild AEs (headache). All treatments were well tolerated.

Conclusions:

In these patients, policosanol (10 mg/d) administered concomitantly with Ω3FA (1 g/d) enhanced the inhibition of platelet aggregation to AA and collagen, but not to epinephrine, compared with Ω3FA+Pla, without significantly affecting bleeding time. Concomitant treatment was also associated with reduced levels of LDL-C and TC and raised HDL-C levels. All treatments were well tolerated.     

Impact of Blood Lipids on 10-Year Cardiovascular Risk in Individuals Without Dyslipidemia and With Low Risk Factor Burden

ObjectiveTo determine the association of plasma lipids with the prevalence of subclinical atherosclerosis and 10-year risk of incident cardiovascular (CV) events among healthy individuals without dyslipidemia and with low risk factor burden.Patients and MethodsThe analysis (June 24, 2020, through June 12, 2021) included 1204 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) study who were current nonsmokers and did not have CV disease, hypertension (blood pressure ≥130/80 mm Hg or antihypertensive use), diabetes (fasting glucose ≥126 mg/dL or glucose-lowering medication use), and dyslipidemia (low-density-lipoprotein-cholesterol [LDL-C] ≥160 mg/dL, high-density-lipoprotein-cholesterol [HDL-C] <40 mg/dL, total cholesterol [TC] ≥240 mg/dL, triglycerides [TGs] ≥150 mg/dL, or lipid-lowering medication use) at baseline. Associations of lipids with baseline atherosclerosis (presence of carotid plaque and/or coronary calcification) and incident CV events over 10 years were examined using multivariable relative risk regression and Cox regression, respectively.ResultsAt baseline, participants’ median age was 54 (IQR, 49 to 62) years, and 10-year CV risk was 2.7% (IQR, 1.0% to 6.6%); 43.4% had subclinical atherosclerosis. A 1-SD higher LDL-C (23.4 mg/dL), TC (24.7 mg/dL), non–HDL-C (25.3 mg/dL), TC/HDL-C (0.75), and LDL-C/HDL-C (0.66) was associated with a higher prevalence of atherosclerosis of between 6% and 9% (P<.05). For every 1-SD higher LDL-C, non–HDL-C, TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C (0.49), the 10-year incidence of CV events was significantly increased by 40%, 44%, 51%, 49%, and 39%, respectively. For every 1-SD lower HDL-C (13.5 mg/dL), CV risk was increased by 37%. Triglycerides had no association with either outcome.ConclusionExcept for TGs, all lipid variables were associated with atherosclerosis and future risk of CV disease among persons without dyslipidemia and with low risk factor burden.     

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.     

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.     

The Effect of Anastrozole on the Lipid Profile: Systematic Review and Meta-analysis of Randomized Controlled Trials

PurposeWe aimed to investigate the impact of anastrozole administration on the traditional components of the lipid profile (ie, total cholesterol [TC], LDL-C, HDL-C, and triglycerides [TGs]) by means of a systematic review and meta-analysis of randomized controlled trials.MethodsWe searched the PubMed/Medline, Scopus, Embase, and Web of Science databases for relevant randomized controlled trials published in the English language until January 18, 2022. The weighted mean difference (WMD) and 95% CIs were calculated using a random-effects model (DerSimonian and Laird methods).FindingsAnastrozole administration significantly lowered TC concentrations when the treatment duration was ≤3 months (WMD = ?2.73 mg/dL; 95% CI, ?5.09 to ?0.38 mg/dL; P = 0.02) and when the baseline TC concentration was ≥200 mg/dL (WMD = ?3.64 mg/dL; 95% CI, ?6.30 to ?0.98 mg/dL; P = 0.007). HDL-C levels decreased after anastrozole administration when the treatment duration was >3 months (WMD = ?1.67 mg/dL; 95% CI, ?3.24 to ?0.10 mg/dL; P = 0.03). Anastrozole administration had no impact on TG or LDL-C values.ImplicationsAnastrozole administration in humans can decrease TC and HDL-C levels but has no effect on LDL-C or TG concentrations.     

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     

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.     

Hemostatic effects of atorvastatin versus simvastatin

OBJECTIVE: To compare the effects of simvastatin and atorvastatin on hemostatic parameters. METHODS: Sixty-one patients with primary hypercholesterolemia without coronary heart disease were treated with atorvastatin 10-20 mg/d or simvastatin 10-20 mg/d. At baseline, 4, 12, and 24 weeks, lipid levels such as low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triglycerides (TGs), and hemostatic parameters such as platelet counts, partial thromboplastin time (PTT) prothrombin time (PT), and fibrinogen levels were measured. RESULTS: At 12 weeks, the doses of the statins were increased to 20 mg/d in 10 of 35 (28.5%) patients treated with atorvastatin and 18 of 26 (69.2%) patients treated with simvastatin when the target level of LDL-C (130 mg/dL) was not reached. Mean doses were atorvastatin 12.8 mg/d and simvastatin 16.9 mg/d. After 24 weeks, 5 patients (14.3%) in the atorvastatin group and 4 patients (15.3%) in the simvastatin group had not reached the goal. In patients with diabetes, target level (LDL-C <100 mg/dL) was not reached in 35.7% of patients in the atorvastatin group and 44.4% of patients in the simvastatin group. Both simvastatin and atorvastatin were effective in lowering TC and LDL-C levels (p < 0.001). Atorvastatin lowered TGs significantly (p < 0.01). Neither atorvastatin nor simvastatin significantly reduced VLDL-C levels. HDL-C levels increased with atorvastatin, but there was no significant difference between the 2 groups. Platelet counts decreased with both statins nonsignificantly. Moreover, fibrinogen levels decreased with simvastatin and atorvastatin, but these reductions were significant only for simvastatin (p < 0.05). We detected prolongation of the PT with both drugs (p < 0.05); however, prolongation of the PTT was significant only with simvastatin (p < 0.001). Effectiveness of both statins on lipid and hemostatic parameters was dose related. Adverse effects were seen in 5 patients (14.2%) treated with atorvastatin and 3 patients (11.5%) treated with simvastatin. Elevations in serum transaminase levels >3 times the upper limit of normal and in creatine phosphokinase >5 times the upper limit of normal were not observed in any group. CONCLUSIONS: Atorvastatin was more effective than simvastatin on lipid parameters, although statistically insignificantly, while simvastatin produced more significant changes than atorvastatin on hemostatic parameters. The mean dose of simvastatin was greater than that of atorvastatin. Both statins had increased effects on lipid and hemostatic parameters when doses were increased. Atorvastatin and simvastatin were well tolerated. Different effects of statins on lipid levels and on coagulation parameters should be considered in patients with hypercholesterolemia and tendency to coagulation, especially in preventing thrombotic events. Further studies in larger trials are needed to confirm these observations.     

Effect of rosuvastatin on concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma high-sensitivity C-reactive protein in hypercholesterolemic patients with and without type 2 diabetes mellitus: A 12-week, open-label, pilot study

Background: Oxidative stress and inflammation of the arterial wall are now recognized as important factors in the progression of atherosclerosis. C-reactive protein (CRP) has been defined as a sensitive but not specific marker of inflammation. Statin therapy has been reported to decrease plasma high-sensitivity CRP (hs-CRP) concentration in hypercholesterolemic patients.Objective: The aim of this study was to examine the effect of rosuvastatin on concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma hs-CRP in hypercholesterolemic patients with and without type 2 diabetes mellitus.Methods: Patients with hypercholesterolemia with and without type 2 diabetes mellitus were enrolled in this pilot study after written informed consent was given. At baseline and after 12 weeks of open-label treatment with rosuvastatin 2.5 mg/d, concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma hs-CRP were measured. Urine 8-iso-prostaglandin F_2α (8-iso-PGF_2α) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations were also measured to asess whole-body oxidative stress. Plasma free-radical generation was estimated using a total reactive oxygen species (TROS) assay system. Adverse effects were assessed at each study visit (4-week intervals) through patient interviews and laboratory testing.Results: Thirty-five patients were enrolled with 1 dropping out prior to study completion; therefore, 34 patients (19 women, 15 men; mean [SE] age, 55.4 [13.6] years; range, 30–78 years) completed the study. Compared with baseline, significant decreases were found in serum concentrations of total cholesterol (TC) (252.3 [39.3] vs 187.8 [30.1] mg/dL; P < 0.001; Δ = 24.5%), LDL-C (162.0 [44.3] vs 98.5 [31.9] mg/dL; P < 0.001; Δ = 38.7%), and triglycerides (TG) (157.2 [93.6] vs 124.4 [69.9] mg/dL; P < 0.05; Δ = 11.7%) after 12 weeks of treatment with rosuvastatin. Serum HDL-C concentration did not change significantly from baseline (59.7 [20.5] vs 63.7 [19.3] mg/dL; Δ = 9.4%). The plasma LDL-C/HDL-C ratio decreased significantly after rosuvastatin treatment (3.03 [1.33] vs 1.72 [0.83]; P < 0.001; Δ = 43.2%). Compared with baseline, significant decreases were observed in urine concentrations of the oxidative stress markers after 12 weeks of rosuvastatin treatment: 8-iso-PGF_2α (342.8 [154.3] vs 300.6 [101.2] pg/mg; P < 0.05) and 8-OHdG (11.1 [4.53] vs 8.1 [2.7] ng/mg; P < 0.01). TROS decreased significantly (182.3 [29.0] vs 157.6 [17.3] U; P < 0.001), and plasma hs-CRP concentration also decreased significantly (0.107 [0.100] vs 0.054 [0.033] mg/dL; P < 0.05). When the patients' results were assessed according to the presence or absence of type 2 diabetes mellitus, urine 8-iso-PGF_2α concentration was significantly decreased from baseline only in the nondiabetic group. No adverse events were reported or observed during the course of the study.Conclusion: Rosuvastatin treatment was associated with significant reductions in plasma concentrations of TC, LDL-C, and TG, urine and plasma oxidative stress markers, and plasma hs-CRP in these hypercholesterolemic patients.     

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.     

Apolipoprotein B versus LDL-cholesterol: Association with other risk factors for atherosclerosis

Objective

To characterize the differences in various risk factors for atherosclerosis between individuals with apoB higher (H) and lower (L) than predicted from regression equation apoB vs LDL-C.

Methods

We evaluated 391 dyslipidemic subjects not treated with hypolipidemic drugs. The measured parameters included lipid profile, apolipoproteins A-1 and B, markers of insulin resistance and inflammation/hemostasis.

Results

Correlation coefficient between apoB and LDL-C was 0.9 (p < 0.0001). Individuals with H apoB compared to L apoB had significantly higher sex and age adjusted BMI, waist circumference, insulin, HOMA (fasting insulin ? glucose/22.5), C-peptide, proinsulin, PAI-1, sICAM-1, sVCAM-1, t-PA, vWF, frequency of metabolic syndrome and lower values of TC, LDL-C and HDL-C (p < 0.05 to < 0.001 for all parameters).

Conclusion

Individuals with apoB higher than predicted by their LDL-C levels are more insulin resistant and have more atherogenic risk profile. Thus, at least for dyslipidemic patients with high cardiometabolic risk, apoB is a more appropriate marker of risk than LDL-C.     

The Effect of Raloxifene Treatment on Lipid Profile in Elderly Individuals: A Systematic Review and Meta-analysis of Randomized Clinical Trials

PurposeTo perform a systematic review and meta-analysis of randomized clinical trials (RCTs) to elucidate the effects of raloxifene on the lipid profile in elderly individuals.MethodsA systematic review and meta-analysis of RCTs was performed following the PRISMA statement. Data on triglycerides (TGs), total cholesterol (TC), HDL-C, and LDL-C were extracted. Relevant publications up to October 2020 were detected through searches in the PubMed/MEDLINE, Web of Science, Scopus, and Embase databases. Changes were reported as weighted mean differences (WMDs) and 95% CIs using random-effects models.FindingsNine studies were selected, with a duration of intervention ranging from 2 and 12 months and a raloxifene dose of 60 to 120 mg/d. Studies were performed in healthy individuals and in those with disorders, such as osteoporosis, type 2 diabetes, and kidney disease required long-term hemodialysis. Overall, TG (WMD, −6.50 mg/dL; 95% CI, −34.18 to 21.20 mg/eL; P = 0.646), LDL-C (WMD, −17.86 mg/dL; 95% CI, −42.44 to 6.72 mg/dL; P = 0.154), and HDL-C (WMD, 2.35 mg/dL; 95% CI, −1.14 to 5.84 mg/dL; P = 0.187) levels did not change significantly after the administration of raloxifene. In contrast, TC levels decreased after raloxifene therapy (WMD, −6.59 mg/dL; 95% CI, −13.13 to −0.05 mg/dL; P = 0.048).ImplicationsRaloxifene therapy decreased TC levels but did not alter TG, HDL-C, and LDL-C concentrations in elderly individuals. Regarding the LDL-C levels, although the finding lacked statistical significance, we believe that there was a mean reduction that deserves further clinical attention as much as TC.     

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.     

Antihypercholesterolemic effects of atorvastatin in patients previously receiving other 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors: an open-label study

Background: Atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was introduced in Japan in May 2000 with purportedly potent cholesterol-lowering effects. However, only a handful of studies have assessed its efficacy and tolerability in Japanese patients.Objective: This study was conducted to assess the efficacy and tolerability of atorvastatin in Japanese patients with hypercholesterolemia.Methods: Outpatients at the Hiramitsu Clinic who were receiving HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia were enrolled in this open-label study. Previous HMG-CoA reductase inhibitor therapy was discontinued, and patients were uniformly switched to atorvastatin 10 mg/d with no intervening washout period. Clinical laboratory values and serumlipid levels were used as safety indices, and achievement rates of target total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were used to assess efficacy. Target TC/HDL-C levels in patients with Japan Atherosclerosis Society category B hypercholesterolemia (patients with risk factors) and category C hypercholesterolemia (patients with coronary heart disease) were <200/<120 mg/dL and <180/<100 mg/dL, respectively.Results: Seventy-nine patients (23 men, 56 women; mean [±SD] age, 63.9 ± 11.2 years) completed the study. The mean duration of atorvastatin therapy was 62.7 ± 9.0 days. The switch to atorvastatin produced significant reductions in mean levels of TC (from 212.8 ± 29.0 mg/dL to 165.7 ± 24.8 mg/dL; P < 0.001) and LDL-C (from 135.2 ± 24.3 mg/dL to 92.2 ± 20.7 mg/dL; P < 0.001). Achievement rates of target TC and LDL-C levels dramatically improved in patients with Japan Atherosclerosis Society category B or C hypercholesterolemia. In patients with category B hypercholesterolemia, the achievement rate improved from 30.8% (20/65) at baseline to 87.7% (57/65) with regard to target TC levels and from 26.2% (17/65) to 92.3% (60/65) with regard to target LDL-C levels. In category C, the corresponding results were 30.0% (3/10) to 80.0% (8/10) and 10.0% (1/10) to 70.0% (7/10). No side effects sufficiently serious to warrant discontinuation of atorvastatin therapy were observed.Conclusion: In this study, atorvastatin was effective and well tolerated for the treatment of hypercholesterolemia in Japanese patients.