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Although the role of high-intensity lipid-lowering therapy in cardiovascular protection has broadened, concerns still exist about new-onset diabetes mellitus (NODM), especially in vulnerable patients. This study aimed to compare the effect of high-dose (4 mg/d) and usual dose (2 mg/d) pitavastatin on glucose metabolism in patients with hyperlipidemia and impaired fasting glucose (IFG). In this 12-month study, glucose tolerance and lipid-lowering efficacy of high-dose pitavastatin (4 mg [study group]) was compared with that of usual dose pitavastatin (2 mg [control group]) in patients with hyperlipidemia and IFG. The primary end point was the change of glycosylated hemoglobin (HbA 1c) after 24 weeks of treatment. The secondary end points were as follows: (1) NODM within 1 year after treatment, (2) change of lipid parameters, (3) changes of adiponectin, and (4) change of blood glucose and insulin levels. Of the total 417 patients screened, 313 patients with hypercholesterolemia and IFG were randomly assigned into groups. The mean (SD) change in HbA 1c was 0.06% (0.20%) in the study group and 0.03% (0.22%) in the control group (P = 0.27). Within 1 year, 27 patients (12.3%) developed NODM, including 12 (10.6%) of 113 patients in the study group and 15 (14.2%) of 106 in the control group (P = 0.43). The study group had a significantly higher reduction of total cholesterol and LDL-C levels and a higher increase in apolipoprotein A1/apolipoprotein B ratio (0.68 [0.40] vs 0.51 [0.35], P < 0.01). The high-dose pitavastatin therapy did not aggravate glucose metabolism compared with the usual dose therapy. Moreover, it had a better effect on cholesterol-lowering and apolipoprotein distribution in the patients with hyperlipidemia and IFG. [ABSTRACT FROM AUTHOR]

Purpose This study evaluates the effectiveness of pitavastatin in patients with atherosclerosis. Methods Sixty patients with atherosclerosis with lipid-rich carotid plaques were included and allocated into low-dose (2 mg/d) and high-dose (4 mg/d) pitavastatin groups with 48 weeks of treatment. Total cholesterol, LDL-C, HDL-C, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein (a), and the inflammation-related factors interleukin 6, high-sensitivity C-reactive protein, and homocysteine were determined. High-resolution (3.0-T) magnetic resonance imaging was used to evaluate the lipid core area, plaque thickness, total vessel area, lumen area, wall area, and normalized wall index. Findings After the treatment period, the blood serum values were improved in both groups, but the improvement was significantly better for total cholesterol ( P < 0.009), HDL-C, LDL-C, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein (a), and homocysteine (all P < 0.001) in the high-dose group. The high-resolution magnetic resonance images revealed great improvements in both groups, although significantly better for the lipid core area ( P < 0.001), plaque thickness ( P < 0.001), wall area ( P < 0.05), normalized wall index ( P < 0.001), and lumen area ( P < 0.05) in the HD group. Further analyses revealed a close correlation between lipid-rich plaques and changes in blood lipid components. Implications Pitavastatin had significant lipid-lowering and anti-inflammatory effects in patients with atherosclerosis. It also reduced the lipid components and plaques of lipid rich carotid plaques. The effect was obviously stronger in the high-dose than in the low-dose group. [ABSTRACT FROM AUTHOR]

Purpose: Results from a Phase III, European, noninferiority trial in elderly (age ≥ 6 5 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 < 6 5 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. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to show that the efficacy of 1PC111 is superior to that of either ezetimibe or pitavastatin alone (monotherapy) for the treatment of hypercholesterolemia., Methods: This was a multicenter, randomized, double-blind, Phase III study. Patients with hypercholesterolemia or mixed dyslipidemia were randomized to receive 1PC111 (which was a fixed-dose combination of pitavastatin 2 mg and ezetimibe 10 mg), pitavastatin 2 mg, or ezetimibe 10 mg daily for 12 weeks. The primary end point was the difference in the percent change in LDL-C from baseline to week 12 between the 1PC111 and each monotherapy group. The secondary end points were the percent change in other lipid profiles from baseline to each visit. All patients were assessed for adverse events until end of study., Findings: A total of 388 patients were randomly assigned to the 1PC111 (n = 128), pitavastatin (n = 132), or ezetimibe (n = 128) group. Generally, baseline characteristics were similar among the 3 groups. A statistically significant decrease in the LDL-C level at week 12 was observed in the 1PC111 group (-50.50% [14.9%]) compared with either the pitavastatin (-36.11% [11.4%]; P < 0.001) or ezetimibe (-19.85% [12.4%]; P < 0.001) group. Also, there was a statistically significant difference between 1PC111 and each monotherapy group in the reduction in total cholesterol, non-HDL-C, and apolipoprotein B levels. Moreover, there was a trend toward more efficient lowering of LDL-C levels in elderly patients (age ≥65 years) than in younger patients (age <65 years) by 1PC111 treatment. In patients given a class I recommendation for atherosclerotic cardiovascular disease prevention, the percentage of patients achieving the LDL-C target of <100 mg/dL at week 12 was significantly higher in the 1PC111 group than in both monotherapy groups (P < 0.001). Overall, the incidence of adverse events was similar among 3 groups., Implications: 1PC111 was more effective in improving lipid profiles and achieving the LDL-C goal than pitavastatin or ezetimibe alone for hypercholesterolemia treatment. Furthermore, 1PC111 may provide more benefit in treating elderly patients., Clinicaltrials: gov identifier: NCT04643093., Competing Interests: Declarations of Interest Dr Jong has received honoraria for lectures from Orient EuroPharma, Novartis, Pfizer, and Merck. Dr Chao has received honoraria for lectures from Orient EuroPharma. The other authors have indicated that they have no conflicts of interest of grants, honoraria, consultancies, speakers bureau or advisory board positions, or significant stock holdings received from industry or organizations, regarding the content of this article. The study sponsor had a role in the study design: the collection, analysis, and interpretation of data. The decision to submit the manuscript for publication was made by the authors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Pitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia., Methods: Korean men and women aged >19 and <80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4-8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients., Findings: The percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (-52.8% [11.2%]) and pooled pitavastatin (-37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C-lowering effect than that with pitavastatin (difference, -15.8 mg/dL; 95% CI, -18.7 to -12.9; P < 0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P < 0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups., Implications: Pitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by >50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy., Clinicaltrials: gov identifier: NCT04584736., Competing Interests: Declaration of Interest The authors have indicated that they have no conflicts of interest regarding the content of this article. The sponsor supplied the investigational products and funded the laboratory tests and clinical research coordinator expenses. The funding source had no involvement in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication., (Copyright © 2022. Published by Elsevier Inc.)

Abstract: Background: Pitavastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, and valsartan, an angiotensin receptor blocker, are used concurrently in some patients who are both hyperlipidemic and hypertensive. However, to date, no published studies have explored whether there is an interaction between pitavastatin and valsartan. Objective: The aim of this study was to investigate the potential pharmacokinetic interaction between pitavastatin and valsartan in healthy male volunteers in Korea. Methods: A randomized, open-label crossover study was conducted in healthy male Korean volunteers. In varying sequences, each subject received pitavastatin 2 × 2 mg, valsartan 2 × 160 mg, and both treatments, once daily for 7 consecutive days, with a 7-day washout period between each treatment period. Plasma samples were obtained at steady state for the pharmacokinetic evaluation of pitavastatin and valsartan. Pharmacodynamic assessment included lipid profiles and vital sign measurements (systolic and diastolic blood pressure [SBP and DBP, respectively] and pulse rate [PR]). A safety profile assessment, which included vital sign measurements, ECG, and clinical laboratory testing, was performed in each subject. Results: A total of 24 subjects were enrolled (mean age, 30.5 years [range, 23.0−45.0 years]; mean body weight, 71.2 kg [range, 56.1−86.0 kg]; and mean body mass index, 23.2 kg/m2 [range, 19.2−25.8 kg/m2]). The 95% CIs of the geometric mean ratios of AUCτ and Cmax,ss of pitavastatin were 0.97 to 1.11 and 0.73 to 1.09, respectively. The 95% CIs of the geometric mean ratios of AUCτ and Cmax,ss of valsartan were 0.90 to 1.27 and 0.81 to 1.29. Pitavastatin administered as monotherapy and in combination with valsartan was associated with significantly lowered total cholesterol and LDL-C compared with valsartan monotherapy (both, P < 0.05). Differences in lipid-lowering effects were not statistically significant between pitavastatin monotherapy and pitavastatin combined with valsartan. Valsartan monotherapy and valsartan combined with pitavastatin were associated with significantly lower SBP and DBP compared with baseline (both, P < 0.05), although no significant changes in PR were observed. No significant differences in BP or PR changes were noted between concurrent administration of valsartan monotherapy compared with pitavastatin + valsartan. There were no serious AEs reported, and none of the subjects discontinued the study due to AEs. Conclusions: The pharmacokinetic profiles of pitavastatin and valsartan administered as monotherapy were comparable to combination treatment in these healthy male Korean volunteers, suggesting that individual pharmacokinetic properties are not significantly affected by concurrent administration. The concurrent administration of pitavastatin and valsartan was generally well tolerated. The findings from the present study provide a basis for a larger study in hypertensive patients with hyperlipidemia. ClinicalTrials.gov identifier: NCT01232049. [Copyright &y& Elsevier]

Abstract: Background: Pitavastatin calcium is a new addition to the class of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (“statins”) approved for use in the United States for the treatment of primary hyperlipidemia and mixed dyslipidemia. Objective: The purpose of this review was to evaluate the literature related to the medicinal chemistry, pharmacology, pharmacokinetic properties, clinical efficacy, and tolerability of pitavastatin in the treatment of hyperlipidemia. Methods: A search of MEDLINE, EMBASE, and the Journal Archive for English-language literature was conducted for articles published through January 2011 using the following search terms: itavastatin, Livalo, nisvastatin, NK 104, and pitavastatin. Articles were reviewed if they pertained to the clinical efficacy, pharmacology, pharmacokinetic properties, or tolerability of pitavastatin. Clinical trials were systematically included in the analysis of clinical efficacy if they used a randomized design to study the effects of the drug on hyperlipidemia, hypercholesterolemia, or heart disease. Trials were excluded if they did not signify the statin used, did not pertain to clinical efficacy, or enrolled <20 patients. Results: A total of 16 studies were identified and reviewed for clinical efficacy. Based on findings from pharmacokinetic studies, pitavastatin may be given at any time of the day, with or without food. The drug had a mean plasma elimination t1/2 of 12 hours, is expected to be associated with minimal drug–drug interactions because it is not metabolized by the cytochrome P450 3A4 isozyme, and is primarily excreted unchanged in the bile with little renal elimination. Clinical trials described the effects of pitavastatin on cholesterol, high-sensitivity C-reactive protein (hs-CRP), and progression of atherosclerosis. Pitavastatin at doses of 1 to 4 mg/d was reported to be associated with reductions in LDL-C of 38% to 44% and in triglycerides of 14% to 22%, and with increases in HDL-C of 5% to 8% (all, P < 0.05). Overall, the effect of pitavastatin on cholesterol was comparable to those of atorvastatin and simvastatin at low to intermediate doses. Studies on the effects of pitavastatin on cardiovascular outcomes were lacking. The adverse-events (AE) profile of pitavastatin compared favorably with those of other available statins. AEs included gastrointestinal symptoms (0.7%–2.2%), myopathies (0.3%–1.1%), and elevated hepatic enzyme concentrations (0.0%–8.8%). Conclusions: Based on the findings from previously published clinical trials, pitavastatin is an effective lipid lowering agent and is another therapeutic option of currently available statins. [Copyright &y& Elsevier]

Abstract: Background: Hypercholesterolemia has been identified as an important risk factor for stroke. It has been reported that statins might reduce the risk for new or recurrent cardiovascular events and strokes. Objective: This paper reports on the effects of pitavastatin on cerebral blood flow in 2 elderly patients. Case summary: Two patients, a 72-year-old right-handed Japanese man and a 77-year-old right-handed Japanese woman, both with a history of cerebral infarction, received 6-month treatment with pitavastatin 2 mg/d for complicated hypercholesterolemia. To assess regional cerebral blood flow (rCBF), single-photon emission computed tomography (SPECT) studies with technetium-99m-ethyl cysteinate dimer were carried out before and after pitavastatin administration. Tomography was evaluated using the Easy z Score Imaging System. None of the patients'' other treatments, with the exception of pitavastatin initiation, were modified during the treatment period. In both patients, serum total cholesterol concentrations were improved within 3 months of initiation of pitavastatin treatment, with no marked changes in clinical symptoms. In both patients, improvement was found in rCBF on SPECT. The z score of the left parietal lobe in 1 patient was improved, from 2.20 to 1.69. That of the other patient was also improved, from 2.42 to 1.94. Conclusion: In both patients, clinically significant improvement in rCBF was found after 6-month treatment with pitavastatin 2 mg/d. [Copyright &y& Elsevier]

Abstract: Background: Statin therapy has been found to produce substantial reductions in low-density lipoprotein cholesterol (LDL-C) levels, resulting in a reduced risk for cardiovascular events. Recently, research interest has focused on modification of high-density lipoprotein cholesterol (HDL-C) levels for the potential prevention of cardiovascular events. The effects of pitavastatin and atorvastatin on HDL-C have not been directly compared. Objectives: This study compared the effects of pitavastatin and atorvastatin on HDL-C and other lipids and glucose metabolism in Japanese patients with elevated LDL-C levels and glucose intolerance. The tolerability of the 2 treatments was also compared. Methods: This was a multicenter, open-label, parallelgroup trial. Patients with LDL-C levels ≥ 140 mg/dL and glucose intolerance (defined according to Japanese criteria for borderline diabetes and World Health Organization criteria for impaired fasting glucose and impaired glucose tolerance) were randomly assigned to receive either pitavastatin 2 mg/d or atorvastatin 10 mg/d for 52 weeks. Levels of serum lipids and lipoproteins and measures of glucose metabolism (fasting insulin, fasting glucose, glycosylated hemoglobin, and homeostasis model assessment for insulin resistance) were obtained at baseline and at 8, 26, and 52 weeks of treatment. The effect of study drug on glucose metabolism was evaluated as a tolerability outcome. Tolerability was further assessed based on adverse events, either spontaneously reported or elicited by questioning; physical examination findings; and clinical laboratory test results. Study physicians rated the relationship of adverse events to study medication as unrelated, suspected, or probable. Results: Two hundred seven patients were enrolled in the study, and efficacy was evaluated in 173 patients (88 pitavastatin, 85 atorvastatin). Thirty-four patients were excluded for reasons including failure to start medication or lack of ≥ 6 months of follow-up. Women accounted for 62% (108/173) of the evaluable population, which had a mean age of 63.3 years and a mean weight of 63.0 kg; 89% (154/173) had diabetes mellitus. The percent change in HDL-C levels was significantly greater in the pitavastatin group compared with the atorvastatin group (8.2 vs 2.9, respectively; P = 0.031), as was the percent change in apolipoprotein (Apo) A-I (5.1 vs 0.6; P = 0.019). The percent change in LDL-C levels was significantly lower with atorvastatin compared with pitavastatin (−40.1 vs −33.0, respectively; P = 0.002), as were the percent changes in non-HDL-C (−37.4 vs −31.1; P = 0.004), Apo B (−35.1 vs −28.2; P < 0.001), and Apo E (−28.1 vs −17.8; P < 0.001). The significant results for these parameters were unchanged when all 189 subjects who received ≥ 1 dose of study medication were included in the analysis, using last-value-carried-forward methodology. There were no significant differences between treatments with respect to the measures of glucose metabolism. Both statins appeared to be well tolerated. Adverse events occurred in 9% (9/96) of the pitavastatin group and 14% (13/93) of the atorvastatin group (P = NS). Two patients in the pitavastatin group and none in the atorvastatin group had an alanine aminotransferase value >3 times the upper limit of normal (P = NS). Conclusions: In these patients with elevated LDL-C levels and glucose intolerance, 52 weeks of treatment with pitavastatin 2 mg/d was associated with significantly greater increases in HDL-C and Apo A-I levels than atorvastatin 10 mg/d. Both treatments were well tolerated. [Copyright &y& Elsevier]

Abstract: Background: Although previous studies have examined the efficacy of pitavastatin, its tolerability and effects on lipid concentrations have not been compared with those of atorvastatin in a multicenter, randomized study. Objective: This trial compared the efficacy and tolerability of pitavastatin and atorvastatin in hypercholesterolemic Korean adults. Methods: This 8-week, multicenter, randomized, open-label, dose-titration study was conducted at 18 clinical centers in Korea between May 2005 and February 2006. After a 4-week dietary lead-in period, patients with hypercholesterolemia were randomized to receive either pitavastatin 2 mg/d or atorvastatin 10 mg/d. Patients who had not reached the low-density lipoprotein cholesterol (LDL-C) goal by week 4 received a double dose of the assigned medication for an additional 4 weeks. Efficacy was evaluated in terms of achievement of the National Cholesterol Education Program Adult Treatment Panel III LDL-C goals and changes from baseline in other lipids and high-sensitivity C-reactive protein (hs-CRP). The tolerability profile was assessed by physical and electro-cardiographic examinations, laboratory tests, and recording adverse reactions at all visits. Results: A total of 268 patients were randomized to treatment, and 222 (82.8%) completed the study (149 women, 73 men; mean age, 59 years; mean weight, 63.5 kg). At the end of the study, there was no significant difference between the pitavastatin and atorvastatin groups in the proportion of patients achieving the LDL-C goal (92.7% [102/110] vs 92.0% [103/112], respectively). In addition, there were no significant differences between groups in terms of the percent changes from baseline in LDL-C, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), or hs-CRP. Twenty-six of 136 patients (19.1%) taking pitavastatin reported 35 treatment-emergent adverse reactions; 33 of 132 patients (25.0%) taking atorvastatin reported 39 treatment-emergent adverse reactions. Elevations in creatine kinase were observed in 6 patients (4.4%) in the pitavastatin group and 7 patients (5.3%) in the atorvastatin group. There were no serious adverse drug reactions in either group. Conclusions: In these adult Korean patients with hypercholesterolemia, pitavastatin and atorvastatin did not differ significantly in terms of the proportions of patients achieving the LDL-C goal; reductions in LDL-C, total cholesterol, and triglycerides; or increases in HDL-C. Both drugs were well tolerated. [Copyright &y& Elsevier]

Abstract Background:: Pitavastatin is a 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor used to treat hypercholesterolemia. Objective:: The goal of this study was to compare the efficacy and safety of pitavastatin versus those of simvastatin in Korean patients with hypercholesterolemia. Methods:: This was an 8-week, multicenter, prospective, randomized, open-label, Phase III clinical trial. Male and female Korean patients with hypercholesterolemia who were between the ages of 20and 75 years and who had a fasting triglyceride level &#60;600 mg/dLand a low-density lipoprotein (LDL) cholesterol level >130 mg/dLafter a 4-week dietary lead-in period were eligible for entry. Eligible patients were randomized into 2 groups in a 1:1 ratio. Patients received pitavastatin 2 mg once daily or simvastatin 20 mg once daily for 8weeks. The medication was administered initially for 4 weeks, and an additional 4 weeks of study medication was prescribed at week 4. The final visit was conducted 8 weeks after randomization. Results:: Of the 104 patients randomized to treatment, 95 patients (59 women; 36 men) completed the study (49 in the pitavastatin group [meanage, 59.9 years] and 46 in the simvastatin group [mean age, 56.4 years]). No significant difference was found between groups with respect to patient age, sex, or body mass index. There was no significant difference in the percent decrease in LDL cholesterol levels (mean [SD],38.2% [11.6%] decrease for the pitavastatin group vs 39.4% [12.9%] decrease for the simvastatin group [P = 0.648]). Also, therewere no significant differences between the 2 study groups in the percent changes in total cholesterol, triglyceride, or high-density lipoprotein (HDL) cholesterol levels from baseline to study end. No significant difference was observed for the proportion of patients who achieved the LDL cholesterol goal of the National Cholesterol Education Program Adult Treatment Panel III: 93.9% (46/49) of patients in the pitavastatin group and 91.3% (42/46) of patients in the simvastatin group (P = 0.709) met the target level. At least 1 clinical adverse event and at least 1 adverse drug reaction were observed in 25.0%(13/52) and 11.5% (6/52), respectively, of patients in the pitavastatin group, and 37.3% (19/51) and 23.5% (12/51), respectively, in the simvastatin group; this difference was not statistically significant. The most common adverse event was an elevation in creatine kinase levels >2 times the upper limit of normal in 3.8% of pitavastatin-treated patients and 9.8% of simvastatin-treated patients (P = 0.269). There were no serious adverse drug reactions observed in either group. Conclusion:: The HMG-CoA reductase inhibitor pitavastatin was foundto be noninferior to simvastatin in terms of reducing LDL cholesterol, total cholesterol, and triglyceride levels, and increasing HDL cholesterol levels, in Korean patients with hypercholesterolemia after8 weeks of treatment. [Copyright &y& Elsevier]

Dyslipidemia 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. This 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. The 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. In 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. • Lipid profiles except LDL-C cannot be controlled properly at all times with statins. • Combination therapy of pitavastatin/fenofibrate reduces non-HDL-C more effectively. • Combination therapy of pitavastatin/fenofibrate improves other lipid profiles. • Combination therapy was well tolerated compared with monotherapy under the conditions of this study. [ABSTRACT FROM AUTHOR]

Purpose: Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that are implicated in atherosclerosis. We assessed the adequacy of pitavastatin 4 mg and pravastatin 40 mg in reducing atherogenic lipid parameters beyond LDL-C, in particular remnant lipoprotein cholesterol (RLP-C)., Methods: From the Phase IV, multicenter, randomized, double-blind PREVAIL US (A Study of Pitavastatin 4 mg Vs. Pravastatin 40 mg in Patients With Primary Hyperlipidemia or Mixed Dyslipidemia) trial, we examined lipoprotein cholesterol subfractions using Vertical Auto Profile testing and apolipoproteins B and A-I at baseline and 12 weeks. Participants with primary hyperlipidemia or mixed dyslipidemia had LDL-C levels of 130 to 220 mg/dL and triglyceride levels ≤ 400 mg/dL. In this post hoc analysis, changes in lipid parameters were compared by using ANCOVA., Findings: Lipoprotein subfraction data were available in 312 patients (pitavastatin, n = 157; pravastatin, n = 155). Pitavastatin promoted a greater reduction in RLP-C than pravastatin (-13.6 [8.7] vs -9.3 [9.5] mg/dL). Furthermore, the pitavastatin group reported greater reductions in both components of RLP-C (both, P < 0.001): intermediate-density lipoprotein cholesterol (-9.5 [6.3] vs -6.4 [6.6] mg/dL) and very low-density lipoprotein cholesterol subfraction 3 (-4.1 [3.5] vs -2.9 [3.8] mg/dL). There were also greater reductions in the major ratios of risk (apolipoprotein B/apolipoprotein A-I and total cholesterol/HDL-C) (both, P < 0.001). There were no significant changes in HDL-C, its subfractions, or natural log lipoprotein(a)-cholesterol. The mean age was 58.8 ± 8.9 years in the pitavastatin group and 57.0 ± 10.2 years in the pravastatin group., Implications: Compared with pravastatin 40 mg daily, pitavastatin 4 mg provided superior reductions in atherogenic lipid parameters beyond LDL-C, including RLP-C. Future studies are needed investigate the clinical implications of lowering directly measured RLP-C as the principal target. ClinicalTrials.gov identifier: NCT01256476., (Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.)