Baseline In Low-density Lipoprotein Cholesterol Level Research Articles

Effectiveness and safety of Inclisiran in hyperlipidemia treatment: An overview of systematic reviews.

This paper aimed to comprehensively evaluate the effectiveness and safety of Inclisiran in treating hyperlipidemia through an overview of systematic reviews (SRs). The Cochrane Library, EMBASE, PubMed, CNKI, WANGFANG database, VIP database, ClinicalTrials.gov, and ICRT were searched electronically to collect SRs and meta-analysis of Inclisiran in hyperlipidemia treatment from the establishment of the database till May 2022. Two researchers independently screened the relevant literature, then the assessment of multiple systematic reviews tool was made into assess the methodological quality of the included studies. Data extracted were used to perform the study through RevMan5.3 software. The grading of recommendations assessment, development, and evaluation tool was used to grade the quality of the evidence of the outcomes included in the SRs. Prospero ID: CRD 42022326845. A total of 10 relevant SRs were included, involving 7 randomized controlled trials. The assessment results of the assessment of multiple systematic reviews tool suggested that the quality of the SRs included needed to be improved. The reduced level of low-density lipoprotein cholesterol of the experimental group was lower than the control group, and the difference in the amount of effectiveness was statistically significant (MD = -50.13, 95%CI: -56.2 to -44.06, P < .00001). The grading of recommendations assessment, development, and evaluation results showed that out of 27 outcomes, 8 were high-quality, 3 were of medium quality, 6 were of low quality, and 10 were of the most inferior quality. 300mg Inclisiran with 2 injections a year has the best therapeutic effect, which can significantly reduce low-density lipoprotein cholesterol and total cholesterol, and increase high-density lipoprotein cholesterol levels in patients with hyperlipidemia. Inclisiran has a favorable safety profile, with no significant difference in the incidence of adverse reactions compared to a placebo. Most of the adverse effects were associated with the reaction on the injection site.

Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia

Additional lipid-lowering therapy options are needed for patients who cannot achieve sufficient decreases in low-density lipoprotein cholesterol (LDL-C) levels using statins alone or for those who are statin intolerant. To conduct a pooled analysis of phase 3 randomized clinical trials of bempedoic acid vs placebo. This analysis pooled data from 4 double-blind, placebo-controlled randomized clinical trials conducted from 2016 to 2018. Patients were enrolled in North America and Europe. Eligibility criteria included hypercholesterolemia while receiving stable lipid-lowering therapy and high cardiovascular risk or hypercholesterolemia and statin intolerance. Patients were randomized 2:1 to bempedoic acid, 180 mg (n = 2425), or placebo (n = 1198) once daily for 12 to 52 weeks. Primary efficacy end point was percentage change from baseline in LDL-C level at week 12 in the intention-to-treat population. Patients were parsed into 2 groups according to enrollment criteria: (1) patients with hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) or with heterozygous familial hypercholesterolemia (HeFH) or with both and receiving statins and (2) patients with hypercholesterolemia who were statin intolerant receiving maximally tolerated statins. In this analysis of 3623 patients, the overall mean (SD) patient age was 65.5 (9.2) years (similar in both pools). Among patients with ASCVD or HeFH or both, the mean (SD) baseline LDL-C level was 107.6 (32.7) mg/dL. At week 12, the LDL-C level percentage change from baseline was -16.0% with bempedoic acid vs 1.8% with placebo (difference, -17.8%; 95% CI, -19.5% to -16.0%; P < .001). Patients with statin intolerance had a mean (SD) baseline LDL-C level of 144.4 (38.8) mg/dL. The percentage changes in LDL-C levels at week 12 were -23.0% in the bempedoic acid group and 1.5% in the placebo group (difference, -24.5%; 95% CI, -27.8% to -21.1%; P < .001). The decrease in LDL-C levels with bempedoic acid was sustained during long-term follow-up in both pools (patients with ASCVD or HeFH or both receiving a maximally tolerated statin, difference of -12.7% at week 52; patients with statin intolerance, difference of -22.2% at week 24). Decreases in non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein levels were greater with bempedoic acid vs placebo. Treatment-emergent adverse events associated more frequently with bempedoic acid than with placebo included increased blood uric acid level (2.1% vs 0.5%), gout (1.4% vs 0.4%), decreased glomerular filtration rate (0.7% vs <0.1%), and increased levels of hepatic enzymes (2.8% vs 1.3%). Bempedoic acid added to maximally tolerated statins, including moderate- or high-intensity statins or no background statin, was associated with decreased LDL-C levels vs placebo in patients with hypercholesterolemia with an acceptable safety profile. As a nonstatin adjunct or statin alternative, bempedoic acid has potential for use in a broad spectrum of patients. ClinicalTrials.gov Identifiers: NCT02666664, NCT02991118, NCT03001076, and NCT02988115.

Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease

Additional treatment options are needed for patients who do not achieve sufficient reduction in low-density lipoprotein cholesterol (LDL-C) level with available lipid-lowering therapies. To assess the efficacy of bempedoic acid vs placebo in patients at high cardiovascular risk receiving maximally tolerated lipid-lowering therapy. Phase 3, randomized, double-blind, placebo-controlled clinical trial conducted at 91 clinical sites in North America and Europe from November 2016 to September 2018, with a final date of follow-up of September 22, 2018. A total of 779 patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both met randomization criteria, which included LDL-C level 70 mg/dL (1.8 mmol/L) or greater while receiving maximally tolerated lipid-lowering therapy. Patients were randomized 2:1 to treatment with bempedoic acid (180 mg) (n = 522) or placebo (n = 257) once daily for 52 weeks. The primary end point was percent change from baseline in LDL-C level at week 12. Secondary measures included changes in levels of lipids, lipoproteins, and biomarkers. Among 779 randomized patients (mean age, 64.3 years; 283 women [36.3%]), 740 (95.0%) completed the trial. At baseline, mean LDL-C level was 120.4 (SD, 37.9) mg/dL. Bempedoic acid lowered LDL-C levels significantly more than placebo at week 12 (-15.1% vs 2.4%, respectively; difference, -17.4% [95% CI, -21.0% to -13.9%]; P < .001). Significant reductions with bempedoic acid vs placebo were observed at week 12 for non-high-density lipoprotein cholesterol (-10.8% vs 2.3%; difference, -13.0% [95% CI, -16.3% to -9.8%]; P < .001), total cholesterol (-9.9% vs 1.3%; difference, -11.2% [95% CI, -13.6% to -8.8%]; P < .001), apolipoprotein B (-9.3% vs 3.7%; difference, -13.0% [95% CI, -16.1% to -9.9%]; P < .001), and high-sensitivity C-reactive protein (median, -18.7% vs -9.4%; difference, -8.7% [asymptotic confidence limits, -17.2% to -0.4%]; P = .04). Common adverse events included nasopharyngitis (5.2% vs 5.1% with bempedoic acid and placebo, respectively), urinary tract infection (5.0% vs 1.9%), and hyperuricemia (4.2% vs 1.9%). Among patients at high risk for cardiovascular disease receiving maximally tolerated statins, the addition of bempedoic acid compared with placebo resulted in a significant lowering of LDL-C level over 12 weeks. Further research is needed to assess the durability and clinical effect as well as long-term safety. ClinicalTrials.gov Identifier: NCT02991118.

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

BackgroundBococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk.MethodsIn two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months.ResultsAt 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of −56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of –59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001).ConclusionsIn two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389.)

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol

BackgroundIn a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers.MethodsWe conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin–kexin type 9 (PCSK9) levels were available through day 240.ResultsA total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (P<0.001 for all comparisons vs. placebo). The two-dose 300-mg inclisiran regimen produced the greatest reduction in LDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran.ConclusionsIn our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company; ORION-1 ClinicalTrials.gov number, NCT02597127.)

Therapeutic practice patterns related to statin potency and ezetimibe/simvastatin combination therapies in lowering LDL-C in patients with high-risk cardiovascular disease

Statin combination therapy and statin uptitration have been shown to be efficacious in low-density lipoprotein cholesterol (LDL-C) lowering and are recommended for patients with high-risk coronary heart disease (CHD) who do not reach guideline-endorsed LDL-C goals on statin monotherapy. This analysis evaluated treatment practice patterns and LDL-C lowering for patients with CHD/CHD risk equivalent on statin monotherapy in a real-world practice setting in the United States. In this retrospective, observational study, patients with CHD/CHD risk equivalent on statin therapy were identified during 2004 to 2008 in a US managed care database. Prescribing patterns and effect of switching from statin monotherapy to combination ezetimibe/simvastatin therapy vs uptitration to higher statin dose/potency level and no change from initial statin potency on LDL-C lowering were assessed. Percentage of change from baseline in LDL-C levels and odds ratios for LDL-C goal attainment were estimated with analyses of covariance and logistic regression. Of 27,919 eligible patients on statin therapy, 2671 (9.6%) switched to ezetimibe/simvastatin therapy, 11,035 (39.5%) uptitrated statins, and 14,213 (50.9%) remained on the same statin monotherapy. LDL-C reduction from baseline and attainment of LDL-C <100 and <70 mg/dL were substantially greater for patients who switched to ezetimibe/simvastatin therapy (-24.0%, 81.2%, and 35.2%, respectively) than for patients who titrated (-9.6%, 68.0%, and 18.4%, respectively) or remained on initial statin therapy (4.9%, 72.2%, and 23.7%, respectively). The odds ratios for attainment of LDL-C <100 and <70 mg/dL were also higher for patients who switched than for patients who uptitrated and had no therapy change than for patients who titrated vs no therapy change. Similarly, among a subgroup of patients not at LDL-C <100 mg/dL on baseline therapy, attainment of LDL-C <100 and <70 mg/dL was greater for patients who switched than for statin uptitration vs no change, as well as for patients who uptritrated statins vs no therapy change. In this study, LDL-C lowering and goal attainment rates improved substantially for patients with high-risk CHD on statin monotherapy who switched to combination ezetimibe/statin or uptitrated their statin therapies; however, approximately one-third of these patients still did not attain the optional recommended LDL-C goal of <70 mg/dL. Moreover, these higher efficacy lipid-lowering therapies were infrequently prescribed, indicating the need for further assessment of barriers to LDL-C goal attainment in actual practice settings.

Lomitapide: A Review of its Use in Adults with Homozygous Familial Hypercholesterolemia

Lomitapide (Juxtapid(TM)), an orally administered inhibitor of the microsomal triglyceride transfer protein, inhibits the synthesis of chylomicrons and very low-density lipoprotein, thereby reducing plasma levels of low-density lipoprotein cholesterol (LDL-C). Lomitapide is used to lower lipid levels in adults with homozygous familial hypercholesterolemia, a rare, potentially life-threatening genetic disease that is commonly caused by mutations in the LDL receptor gene or other genes that affect the function of the LDL receptor. In a multinational single-arm, open-label, 78-week, phase III trial, lomitapide reduced mean plasma LDL-C levels by 50% from baseline in 23 evaluable adults with homozygous familial hypercholesterolemia over a 26week treatment period. Reductions from baseline in LDL-C levels were sustained for up to 78weeks with continued lomitapide treatment. In this study, the initial dosage of lomitapide was 5mg once daily for two weeks, with upward titration thereafter to 10, 20, 40, and 60mg at weeks 2, 6, 10, and 14, respectively, or until an individually assessed maximum dosage was achieved. Prior to the start of treatment with lomitapide, other lipid-lowering therapy (including LDL apheresis) was stabilized over a 6-week period, and then continued throughout the lomitapide treatment phase. Lomitapide was generally well tolerated; the most common adverse events in the phase III trial were gastrointestinal events.

Changes in LDL-C levels and goal attainment associated with addition of ezetimibe to simvastatin, atorvastatin, or rosuvastatin compared with titrating statin monotherapy

BackgroundMany high-risk coronary heart disease (CHD) patients on statin monotherapy do not achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals, and combination lipid-lowering therapy may be considered for these individuals. The effect of adding ezetimibe to simvastatin, atorvastatin, or rosuvastatin therapy versus titrating these statins on LDL-C changes and goal attainment in CHD or CHD risk-equivalent patients was assessed in a large, managed-care database in the US.MethodsEligible patients (n = 17,830), initially on statin monotherapy who were ≥18 years with baseline and follow-up LDL-C values, no concomitant use of other lipid-lowering therapy, and on lipid-lowering therapy for ≥42 days, were identified between November 1, 2002 and September 30, 2009. The percent change from baseline in LDL-C levels and the odds ratios for attainment of LDL-C <1.8 and <2.6 mmol/L (70 and 100 mg/dL) were estimated using an analysis of covariance and logistic regression, respectively, adjusted for various baseline factors.ResultsLDL-C reductions from baseline and goal attainment improved substantially in patients treated with ezetimibe added onto simvastatin, atorvastatin, or rosuvastatin therapy (n = 2,312) versus those (n = 13,053) who titrated these statins. In multivariable models, percent change from baseline in LDL-C was −13.1% to −14.8% greater for those who added ezetimibe onto simvastatin, atorvastatin, or rosuvastatin versus those who titrated. The odds of attaining LDL-C <1.8 and <2.6 mmol/L (70 and 100 mg/dL) increased by 2.6–3.2-fold and 2.5–3.1-fold, respectively, in patients who added ezetimibe onto simvastatin, atorvastatin, or rosuvastatin versus titrating statins.ConclusionCHD/CHD risk-equivalent patients in a large US managed-care database, who added ezetimibe onto simvastatin, atorvastatin, or rosuvastatin, had greater LDL-C reductions and goal attainment than those who uptitrated these statin therapies. Our study suggests that high-risk CHD patients in need of more intensive LDL-C lowering therapy may benefit by adding ezetimibe onto statin therapy.

Pitavastatin

Pitavastatin (Livazo®, Livalo®), an inhibitor of HMG-CoA reductase (statin), is indicated for the reduction of elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, in adult patients with primary hypercholesterolaemia and mixed dyslipidaemia, when response to diet and other non-pharmacological measures is inadequate. Pitavastatin has a favourable pharmacological profile following oral administration, including its long half-life (up to 12 hours), selective uptake into hepatocytes and minimal metabolism by cytochrome P450 (CYP) enzymes. This latter property decreases the likelihood of drug-drug interactions with agents that are metabolized by, inhibit or induce CYP enzymes. Pitavastatin improved the lipid profile (including LDL-C, TC and high-density lipoprotein cholesterol levels) in patients with hypercholesterolaemia and mixed dyslipidaemia, according to large, pivotal phase III studies of up to 60 weeks' duration. In these trials, pitavastatin for 12 weeks was noninferior to simvastatin and atorvastatin in terms of the improvement from baseline in LDL-C levels. In similarly designed trials, pitavastatin improved lipid profiles and was noninferior to simvastatin in patients with high cardiovascular risk and demonstrated significantly greater LDL-C reduction than pravastatin in elderly patients. Furthermore, in patients with type 2 diabetes mellitus, although noninferiority criteria for the comparison with atorvastatin were not met in terms of the improvement from baseline in LDL-C levels, pitavastatin was associated with some improvements in the lipid profile. Pitavastatin also demonstrated substantial lipid-modifying effects in exclusively Asian populations in well designed clinical trials. Pitavastatin was generally well tolerated in clinical trials of up to 60 weeks' duration, with a tolerability profile generally similar to that of atorvastatin and simvastatin. Therefore, pitavastatin appears to be an attractive alternative for the treatment of patients with primary hyperlipidaemia or mixed dyslipidaemia who have not responded adequately to diet and other non-pharmacological measures, and may present a useful treatment option in patients requiring polypharmacy, such as those at high risk of cardiovascular disease. Further studies evaluating the effects of pitavastatin on clinical endpoints, such as cardiovascular morbidity and mortality, are required to confirm the longer-term benefits of pitavastatin.

A 50-Week Extension Study on the Safety and Efficacy of Colesevelam in Adults with Primary Hypercholesterolemia

Colesevelam is a bile acid sequestrant that differs structurally from traditional bile acid sequestrants, allowing it to bind bile acids with greater affinity. Studies have shown that colesevelam significantly reduces low-density lipoprotein cholesterol (LDL-C) levels and, in some cases, significantly increases high-density lipoprotein cholesterol (HDL-C) levels in adults with primary hypercholesterolemia. To investigate the safety and efficacy of colesevelam in adults with primary hypercholesterolemia. This multicenter, open-label, titration-based extension study enrolled subjects who completed one of three multicenter, randomized, double-blind, placebo-controlled phase II studies with colesevelam. This study consisted of a 4-week washout/dietary stabilization period, a 50-week open-label treatment period, and a 2-week follow-up period. Ten clinical centers within the US. Males and females 18 years of age or older who had completed a previous short-term (4- or 6-week) phase II clinical study with colesevelam. At week 0 (following a 4-week washout of all lipid-lowering medication), subjects initiated treatment with colesevelam at a dosage of 1.5 g/day. Colesevelam was uptitrated to a maximum dosage of 3.75 g/day as necessary to achieve a 15-30% reduction from baseline in LDL-C level. At week 12, an HMG-CoA reductase inhibitor (statin) or niacin (nicotinic acid) could be added if colesevelam 3.75 g/day was not sufficient to result in a 15-30% reduction from baseline in LDL-C level. The primary efficacy measure was the change in LDL-C level from baseline to week 50 across all treatment regimens. Secondary efficacy parameters included the change and percent change in total cholesterol, HDL-C, and triglyceride levels from baseline to week 50. There were three cohorts analyzed: (i) colesevelam monotherapy (included all subjects who received colesevelam monotherapy, regardless of dose); (ii) all treatment regimens (included all subjects who received colesevelam monotherapy or colesevelam plus low-dose statin or niacin therapy); and (iii) combination therapy (included only subjects who received colesevelam plus low-dose statin therapy). Two additional cohorts were also evaluated: (iv) maximum-dose colesevelam monotherapy (included only subjects who received colesevelam 3.75 g/day monotherapy); and (v) all maximum-dose colesevelam treatment regimens (included all subjects who received colesevelam 3.75 g/day, either as monotherapy or in combination with low-dose statin or niacin therapy). In total, 272 subjects were screened, 260 enrolled, and 186 completed the study. In total, 255 subjects were included in the intent-to-treat population. The maximum dosage of colesevelam (3.75 g/day) was taken by 50% of subjects (n = 94/188) at week 50; only 38 subjects received low-dose statin or niacin by study end. At week 50, LDL-C levels were significantly (p < 0.001) reduced from baseline across all treatment regimens (by 29.6 mg/dL [from 185.8 to 156.2 mg/dL; 15.0%]). Colesevelam also significantly reduced total cholesterol levels and significantly increased HDL-C and triglyceride levels across all treatment regimens (p < 0.001 for all). Drug-related adverse events were reported by 36.2% of subjects across all treatment regimens (and by 47.4% of subjects who received colesevelam plus low-dose statin or niacin therapy). In this study, colesevelam was found to be safe and effective for the management of LDL-C levels in adults with primary hypercholesterolemia.

Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia--Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR).

BackgroundMany patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C) goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg) and atorvastatin (20 mg) in high-risk patients with hypercholesterolemia.MethodsA total of 996 patients with hypercholesterolemia (LDL-C ≥ 3.4 and < 5.7 mmol/L [130 and 220 mg/dL]) and coronary heart disease (CHD), atherosclerosis, or a CHD-risk equivalent were randomized to once-daily rosuvastatin 10 mg or atorvastatin 20 mg. The primary endpoint was the percentage change from baseline in LDL-C levels at 6 weeks. Secondary endpoints included LDL-C goal achievement (National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] goal < 100 mg/dL; 2003 European goal < 2.5 mmol/L for patients with atherosclerotic disease, type 2 diabetes, or at high risk of cardiovascular events, as assessed by a Systematic COronary Risk Evaluation (SCORE) risk ≥ 5% or 3.0 mmol/L for all other patients), changes in other lipids and lipoproteins, cost-effectiveness, and safety.ResultsRosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p < 0.05). Significantly more patients achieved NCEP ATP III and 2003 European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 20 mg (68.8% vs. 62.5%, p < 0.05; 68.0% vs. 63.3%, p < 0.05, respectively). High-density lipoprotein cholesterol was increased significantly with rosuvastatin 10 mg versus atorvastatin 20 mg (6.4% vs. 3.1%, p < 0.001). Lipid ratios and levels of apolipoprotein A-I also improved more with rosuvastatin 10 mg than with atorvastatin 20 mg. The use of rosuvastatin 10 mg was also cost-effective compared with atorvastatin 20 mg in both a US and a UK setting. Both treatments were well tolerated, with a similar incidence of adverse events (rosuvastatin 10 mg, 27.5%; atorvastatin 20 mg, 26.1%). No cases of rhabdomyolysis, liver, or renal insufficiency were recorded.ConclusionIn high-risk patients with hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin 20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other lipid parameters. Both treatments were well tolerated.