Rosuvastatin Monotherapy Research Articles

Effect of Rosuvastatin Monotherapy and in Combination With Fenofibrate or Omega-3 Fatty Acids on Serum Vitamin D Levels

Low levels of 25(OH) vitamin D [25(OH)VitD] have been recognized as a new cardiovascular disease (CVD) risk factor. Statins seem to increase 25(OH)VitD concentration. To investigate whether combined treatment with the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids would increase 25(OH)VitD levels compared with the high-dose rosuvastatin monotherapy in participants with mixed dislipidemia. We randomly allocated 60 patients with mixed dyslipidemia (low-density lipoprotein cholesterol: >160 mg/dL plus triglycerides: >200 mg/dL) to receive rosuvastatin 40 mg (n = 22), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 21), or rosuvastatin 10 mg plus omega-3 fatty acids 2 g (n = 17) daily for 3 months. Our primary end point was changes in the levels of serum 25(OH)VitD. Rosuvastatin monotherapy was associated with a 53% increase in 25(OH)VitD (from 14.6 [1.0-38.0] to 17.8 [5.3-49.6] ng/mL; P = .000). Rosuvastatin plus micronized fenofibrate and rosuvastatin plus omega-3 fatty acids were associated with increases of 64% (from 14.1 [1.0-48.0] to 18.4 [6.7-52.4] ng/mL, P = .001) and 61% (from 10.4 [6.6-38.4] to 14.0 [9.6-37.6] ng/mL, P = .04), respectively. The changes in 25(OH)VitD after treatment were comparable in the 3 groups. High-dose rosuvastatin monotherapy and the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids are associated with significant and similar increases in the 25(OH)VitD levels. This increase may be relevant in terms of CVD risk prevention.

Attainment of goal/desirable lipid levels in patients with mixed dyslipidemia after 12 weeks of treatment with fenofibric acid and rosuvastatin combination therapy: A pooled analysis of controlled studies

Goal/desirable lipid levels are underachieved in patients with mixed dyslipidemia. These patients may have substantial residual risk of cardiovascular disease even while receiving optimal LDL-C-lowering therapy and may require additional therapy to improve multiple lipid/lipoprotein levels. To evaluate attainment of goal/desirable levels of lipids/lipoproteins after 12-week treatment with combination rosuvastatin+ fenofibric acid versus rosuvastatin monotherapy. This was a post hoc analysis of patients with mixed dyslipidemia who enrolled in one of two randomized controlled trials, and were treated (N= 2066) with rosuvastatin (5, 10, or 20 mg), fenofibric acid 135 mg, or rosuvastatin+ fenofibric acid for 12 weeks. Data were pooled across doses of rosuvastatin as monotherapy and combination therapy. Compared with rosuvastatin monotherapy, combination therapy had comparable effects in achieving risk-stratified LDL-C goals; however, measures of total atherogenic burden were improved because significantly greater percentages of patients attained non-HDL-C goal in high- (62.9% vs 50.4%, P= .006) and moderate-risk groups (87.6% vs 80.4%, P= .016) and apolipoprotein B (ApoB) <90 mg/dL in high-risk group (59.8% vs 43.8%, P < .001). In the overall population, more patients treated with the combination therapy achieved desirable levels of HDL-C >40/50 mg/dL in men/women (P < .001), triglycerides <150 mg/dL (P < .001), and ApoB <90 mg/dL (P < .001), compared with rosuvastatin monotherapy. Furthermore, combination therapy resulted in significantly greater percentages of patients achieving simultaneous specified levels of LDL-C+ non-HDL-C (P< .015); LDL-C+ HDL-C+ TG (P < .001); and LDL-C+ HDL-C+ triglycerides+ non-HDL-C+ ApoB (P < .001), compared with rosuvastatin monotherapy. Rosuvastatin+ fenofibric acid may be more efficacious than rosuvastatin alone in patients with mixed dyslipidemia.

Non-lipid effects of rosuvastatin–fenofibrate combination therapy in high-risk Asian patients with mixed hyperlipidemia

ObjectiveThe aim of this study is to compare the non-lipid effects of rosuvastatin–fenofibrate combination therapy with rosuvastatin monotherapy in high-risk Asian patients with mixed hyperlipidemia. MethodsA total of 236 patients were initially screened. After six weeks of diet and life style changes, 180 of these patients were randomly assigned to receive one of two regimens: rosuvastatin 10mg plus fenofibrate 160mg or rosuvastatin 10mg. The primary outcome variables were the incidences of muscle or liver enzyme elevation. The patients were followed for 24 weeks during drug treatment and for an additional four weeks after drug discontinuation. ResultsThe rates of the primary outcome variables were similar between the two groups (2.8% and 3.9% in the combination and the rosuvastatin groups, respectively, p=1.00). The combination group had more, but not significantly, common treatment-related adverse events (AEs) (13.3% and 5.6%, respectively) and drug discontinuation due to AEs (10.0% and 3.3%, respectively) than the rosouvastatin group. Combination therapy was associated with higher elevations in homocysteine, blood urea nitrogen, and serum creatinine, whereas elevation in alanine aminotransferase was greater in the rosuvastatin group. Leukocyte count and hemoglobin level decreased to a greater extent in the combination group. The combination group showed greater reductions in TG and elevation in HDL-cholesterol. ConclusionIn our study population, the rosuvastatin–fenofibrate combination resulted in comparable incidences of myo- or hepatotoxicity as rosuvastatin monotherapy. However, this combination may need to be used with caution in individuals with underlying pathologies such as renal dysfunction (NCT01414803).

The effects of rosuvastatin alone or in combination with fenofibrate or omega 3 fatty acids on inflammation and oxidative stress in patients with mixed dyslipidemia

Objective:Mixed dyslipidemia, oxidative stress and inflammation are related to a high risk for cardiovascular events. The aim of this open-label randomized study was to compare the effects of high-dose rosuvastatin, low-dose rosuvastatin plus fenofibrate and low-dose rosuvastatin plus omega 3 fatty acids on inflammation and oxidative stress indices in patients with mixed dyslipidemia.Methods:Ninety patients with mixed dyslipidemia participated in the study. Patients were randomly allocated to receive rosuvastatin 40 mg (n = 30, group R), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 30, group RF) or rosuvastatin 10 mg plus omega 3 fatty acids 2 g daily (n = 30, group RΩ). Plasma and high-density lipoprotein (HDL)-associated lipoprotein-associated phospholipase A2 (LpPLA2) activities, high-sensitivity C reactive protein (hsCRP), plasma isoprostane and paraoxonase (PON1) activities were measured at baseline and after 3 months of treatment.Results:Serum concentrations of non-HDL cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly reduced in all study groups. However, these changes were more pronounced in the rosuvastatin monotherapy group. In all treatment groups a significant reduction in total plasma LpPLA2 activity was observed (by 41, 38 and 30% for groups R, RF and RΩ, respectively). This decrease was greater in the R and RF groups compared with the RΩ combination (p < 0.05). HDL-LpPLA2 activity was increased more in the RF group (+43%) compared with the R and RΩ groups (+ 18% and + 35%, respectively; p < 0.05 for both comparisons). In all treatment groups there was a nonsignificant reduction in plasma 8-iso-PGF2α levels. A 53% reduction of hsCRP levels was observed in the R group, while in the RF and RΩ groups the reduction was 28 and 23%, respectively (p < 0.05 and p < 0.01 for the comparisons of group R with groups RF and RΩ, respectively). No significant changes were observed in PON activities in all treatment groups.Conclusion:The greater non-HDL-C- and LDL-C-lowering efficiency of rosuvastatin monotherapy along with its more potent effect on LpPLA2 activity and hsCRP levels indicate that this regimen is a better treatment option for patients with mixed dyslipidemia.

Open‐label, ascending dose, prospective cohort study evaluating the antiviral efficacy of Rosuvastatin therapy in serum and lipid fractions in patients with chronic hepatitis C

HMG CoA reductase inhibition suppresses in vitro HCV replication through depletion of cellular sterol proteins such as geranylgeraniol. Our aims were to prospectively evaluate the changes in serum and lipid fraction HCV RNA with Rosuvastatin in non-responder (NR) patients with CHC. A total of 11 patients with CHC genotype-1 received Rosuvastatin at 20 mg qd (weeks 0-4), 40 mg qd (weeks 5-12), with 4 week follow up. Lipid fractions were separated by a sucrose density gradient ultracentrifugation, HCV RNA determined at wks 0, 2, 4, 8, 12, 16 in serum, and in selected very low- (VLDF) to high-density (HDF) lipid fractions. A reduction in LDL and total cholesterol (TC) was not accompanied by significant decline in HCV RNA. At baseline, there was an inverse correlation between HDL and HCV RNA (ρ = -0.45, P = 0.036). At 20 mg, there was correlation between change (Δ) in TG and Δ HCV RNA (ρ = 0.75, P = 0.007), Δ ALT and Δ TC (ρ = -0.64, P = 0.03) and Δ LDL (ρ = -0.67, P = 0.02). At 40 mg, Δ TG maintained a positive correlation with Δ HCV RNA (ρ = 0.65, P = 0.03). There was a group difference for HCV RNA in relation to lipid fractions (P = 0.04) but not study time intervals (P = 0.17); mean log HCV RNA was greater in VLDF compared to HDF (5.81 ± 0.59 vs 5.06 ± 0.67, P = 0.0002) with no other differences to study time intervals (P = 0.099). Short-term Rosuvastatin monotherapy is not associated with significant changes in serum or lipid fraction HCV RNA in NR patients. HCV co-localizes with the lowest density lipid fractions in serum.

High Doses of Rosuvastatin are Superior to Low Doses of Rosuvastatin Plus Fenofibrate or n‐3 Fatty Acids in Mixed Dyslipidemia

The aim of the study was to compare the efficacy of high-dose rosuvastatin, low-dose rosuvastatin plus fenofibrate and low-dose rosuvastatin plus omega-3 fatty acids with regard to the lipid profile in patients with mixed hyperlipidemia. The primary endpoint was changes in non-high density lipoprotein-cholesterol (non-HDL-C) levels. Study participants were randomly allocated to receive rosuvastatin 40 mg (n = 30, R group), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 30, RF group) or rosuvastatin 10 mg plus n-3 fatty acids 2 g (n = 30, RN group). Non-HDL-C levels were reduced in all groups: in R group by 54%, in RF group by 42% and in RN group by 42%. Significant reductions in total cholesterol (TC), low density lipoprotein (LDL)-C and triglyceride levels were observed in all groups. The reductions in total and LDL-C were greatest in the R group while a more pronounced reduction of triglycerides in the RF group compared with that in the R and the RN group was observed. HDL-C levels were significantly increased only in the RF group. In conclusion, high doses of rosuvastatin and small doses of rosuvastatin plus either fenofibrate or n-3 fatty acids exhibit favorable effects on both LDL-C and non-HDL-C levels. However, rosuvastatin monotherapy more potently reduces these parameters. The combination of rosuvastatin plus fenofibrate leads to a greater decrease in triglyceride levels and a greater increase in HDL-C levels compared with the other two treatments. While awaiting the results of ongoing trials high doses of rosuvastatin may represent the treatment of choice in individuals with mixed dyslipidemia.

Combination Therapy With Ezetimibe/Simvastatin Versus Statin Monotherapy for Low-Density Lipoprotein Cholesterol Reduction and Goal Attainment in a Real-World Clinical Setting

Background Randomized studies have demonstrated improved attainment of target low-density lipoprotein cholesterol (LDL-C) values when ezetimibe is combined with statins for the treatment of hypercholesterolemia. However, the efficacy of an intervention in randomized controlled clinical studies may not correlate with its efficacy in a real-world (community practice) setting. Data to support the LDL-C lowering efficacy of ezetimibe/simvastatin (EZE/SMV) outside of controlled clinical studies are currently lacking. Objective Using patient data from a large, national, administrative claims database, this retrospective observational study evaluated the efficacy of EZE/SMV in lowering LDL-C values and achieving LDL-C target values in newly initiating users and compared the results with those from several statin monotherapies. Methods Patients with hypercholesterolemia who had filled their first prescription for EZE/SMV or statin monotherapy between July 1, 2004, and December 31, 2007, and were ≥18 years old were evaluated. Pertinent data taken from the database included lipid-lowering drug name, date of first prescription, dose, serum lipid levels, and sample dates. Data on cardiovascular history, diabetes, and other concurrent diseases and therapies were also available. Following propensity score matching, multivariate regression models were constructed to estimate the impact of the choice of therapy on key treatment outcomes including the reduction of LDL-C (absolute and percent) as well as the percent of patients achieving goal LDL-C levels as defined by the updated American Heart Association/American College of Cardiology (AHA/ACC) Guidelines for 2006. Results In the total population, both the percent decrease and the absolute reduction in LDL-C values were significantly greater with the use of EZE/SMV than with the 3 statin monotherapies ( P < 0.005 for all comparisons). A significantly greater percentage of patients achieved AHA/ACC LDL-C goals in the first 3 months of EZE/SMV treatment compared with those using each statin monotherapy ( P < 0.05 for all comparisons). Among matched patients with diagnosed diabetes, the percent reduction in LDL-C was also higher with the use of EZE/SMV than with each statin monotherapy ( P < 0.005 for all comparisons). Conclusion In a real-world setting, EZE/SMV appeared to be more effective than simvastatin, atorvastatin, or rosuvastatin monotherapy for attaining therapeutic goals set forth by national and professional societies in patients being initiated on statin-based lipid-lowering therapy.

Efficacy and Safety of Rosuvastatin 5 mg in Combination with Fenofibric Acid 135 mg in Patients with Mixed Dyslipidemia – A Phase 3 Study

Patients with mixed dyslipidemia characterized by elevated low-density lipoprotein cholesterol (LDL-C), elevated triglycerides (TG), and reduced high-density lipoprotein cholesterol (HDL-C) often require combination therapy to improve multiple lipid and nonlipid parameters. This phase 3, multicenter, randomized, double-blind study evaluated the efficacy and safety of rosuvastatin 5mg coadministered with fenofibric acid 135mg in patients with mixed dyslipidemia. A total of 760 patients with TG ≥ 150mg/dL, HDL-C <40mg/dL (<50mg/dL for women), and LDL-C ≥ 130mg/dL were randomized for a 12-week treatment period to rosuvastatin 5mg, fenofibric acid 135mg, or rosuvastatin 5mg + fenofibric acid 135mg. The primary efficacy comparisons were mean percentage changes in HDL-C and TG (rosuvastatin + fenofibric acid vs. rosuvastatin monotherapy), and LDL-C (rosuvastatin + fenofibric acid vs. fenofibric acid monotherapy). Treatment with rosuvastatin + fenofibric acid resulted in statistically significant greater improvements in HDL-C (23.0% vs. 12.4%; P < 0.001) and TG (-40.3% vs. -17.5%; P < 0.001), compared with rosuvastatin monotherapy; and LDL-C (-28.7% vs. -4.1%; P < 0.001), compared with fenofibric acid monotherapy. All secondary efficacy variables improved with combination therapy. Combination therapy was generally well tolerated with a safety profile consistent with individual monotherapies. No unexpected muscle, hepatic, or renal safety signals were identified with combination therapy versus individual monotherapies. In conclusion, rosuvastatin 5mg + fenofibric acid 135mg resulted in comprehensive improvements in the lipid profile of patients with mixed dyslipidemia without unanticipated adverse events.

Switching from Any Statin Brand to Ezetimibe/Simvastatin 10/20 mg is More Effective at Lowering Plasma Lipids Compared with Rosuvastatin 10 mg

Synopsis: Ezetimibe/simvastatin combination and rosuvastatin monotherapy represent two potent lipid-altering treatments for patients with hypercholesterolemia. Purpose: This post-hoc analysis compared the effects of switching from statin monotherapy to ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) vs rosuvastatin 10 mg (ROSUVA) in patient subgroups defined by the brand of prerandomization statin therapy. Methods: In this study, high-risk patients with elevated low-density lipoprotein cholesterol (>2.59 and <4.92 mmol/L) despite statins entered an open-label period and received the same statin brand/dose prior to randomization. Patients were randomized 1:1 to EZE/SIMVA 10/20 mg or ROSUVA 10 mg for 6 weeks. Patient subgroups were defined by the brand of pre-randomization statin therapy (atorvastatin n = 232, rosuvastatin n = 94, simvastatin n = 186, and other [fluvastatin, lovastatin, pravastatin] n = 106). This analysis evaluated % change in lipids/lipoproteins in the patient subgroups. Consistency of the treatment effect across subgroups was evaluated by testing for treatment × subgroup interaction without multiplicity adjustment. Results: Treatment effects across the subgroups were generally consistent with the overall population. EZE/SIMVA was more effective than ROSUVA at lowering low-density lipoprotein, total cholesterol, non-high-density lipoprotein-C, and apoB in the overall population and across the subgroups. Conclusions: Irrespective of statin brand, switching from statins to EZE/SIMVA 10/20 mg vs ROSUVA 10 mg provided superior lipid reductions.Tabled 1Between-treatment differences (EZE/SIMVA – ROSUVA; 95% CI) in least squares mean % change from baseline at study endpoint†Last available post-baseline value collected during the 6-week active treatment period.Overall populationAtorvastatinRosuvastatinSimvastatinOtherP value for treatment-by-subgroup interactionLDL-C (mmol/L)–10.7 (–14.1, –7.3)∗P < .001 EZE/SIMVA vs ROSUVA.–14.3 (–21.2, –7.4)–11.3 (–23.0, 0.5)–7.9 (–14.0, –1.8)–8.0 (–16.0, 0.1).298TC (mmol/L)–7.2 (–9.6, –4.8)∗P < .001 EZE/SIMVA vs ROSUVA.–9.2 (–14.0, –4.4)–7.8 (–15.7, 0.0)–4.8 (–9.2, –0.4)–4.6 (–10.3, 1.1).438non-HDL-C (mmol/L)–9.4 (–12.5, –6.3)∗P < .001 EZE/SIMVA vs ROSUVA.–10.7 (–16.8, –4.5)–9.8 (–20.4, 0.7)–7.7 (–13.7, –1.7)–8.0 (–15.3, –0.8).723apo B (g/L)–8.1 (–10.9, –5.3)∗P < .001 EZE/SIMVA vs ROSUVA.–9.8 (–15.5, –4.1)–9.8 (–19.1, –0.6)–9.4 (–14.7, –4.1)–4.6 (–10.8, 1.7).852∗ P < .001 EZE/SIMVA vs ROSUVA.† Last available post-baseline value collected during the 6-week active treatment period. Open table in a new tab

Abstract 3732: Long-Term Safety and Efficacy of ABT-335 (Fenofibric Acid) in Combination with Statin Therapy for the Treatment of Patients with Mixed Dyslipidemia

Background: The efficacy and safety of ABT-335 + statin combination therapy was demonstrated in three 12-week, controlled studies of patients with mixed dyslipidemia randomized to ABT-335 (135mg) + low or moderate dose rosuvastatin (R), simvastatin (S), or atorvastatin (A), or ABT-335 or statin monotherapy. A subsequent 52-week open label extension study evaluated the long-term safety and efficacy of ABT-335 combined with statins. Methods: Patients who completed 12 weeks of treatment in the 3 controlled studies were eligible to enroll in the 52-week extension study to receive ABT-335 + the moderate dose statin that was used in their initial study: R 20mg, S 40mg, or A 40mg. This was a pre-specified, integrated analysis of patients receiving ABT-335 + statin in the 12- and 52-week studies. Results: Of the 2715 randomized patients, 2316 completed the 12-week studies and 1911 enrolled in the extension study. A total of 2201 patients received at least 1 dose of ABT-335 + statin for a median duration of 364 days; 1139 patients were treated for ≥52 weeks. The incidence of adverse events (AEs) was similar across all 3 combination therapy groups (Table ). The most common AEs were headache, upper respiratory tract infection, nasopharyngitis, and back pain. Rhabdomyolysis was not reported in any group. Patients who were initially randomized to ABT-335 + statin and continued in the extension study (N=979) had sustained improvements in multiple lipids. After 12 and 52 weeks of treatment, combination therapy resulted in mean percent decreases in TG (−45.7% and −47.5%, respectively) and LDL-C (−32.2% and −37.8%), and increases in HDL-C (17.6% and 23.8%). Mean values at 12 and 52 weeks were: TG 141.2 and 136.3 mg/dL; LDL-C 101.6 and 93.5 mg/dL; and HDL-C 45.0 and 47.1 mg/dL, respectively. Conclusions: Long-term ABT-335 + statin combination therapy was generally well tolerated and resulted in comprehensive and sustained improvements in TG, HDL-C, and LDL-C in adults with mixed dyslipidemia. Summary of safety, n/N (%)

Setting a new standard in achieving superior efficacy: ezetimibe + simvastatin

Ezetimibe with simvastatin in combination inhibits both the absorption and production of cholesterol. This dual mechanism of inhibition substantially increases the capacity to decrease levels of atherogenic low-density lipoproteins, compared with that observed when either drug is used alone. Ezetimibe/simvastatin is more effective than atorvastatin or rosuvastatin monotherapy treatments in low-density lipoprotein cholesterol lowering and getting more patients to goals. Ezetimibe/simvastatin offers an important treatment alternative to patients who respond inadequately even to high-dose statin therapy.

Are HIV positive patients resistant to statin therapy?

BackgroundPatients with HIV are subject to development of HIV metabolic syndrome characterized by dyslipidemia, lipodystrophy and insulin resistance secondary to highly active antiretroviral therapy (HAART). Rosuvastatin is a highly potent HMG-CoA reductase inhibitor. Rosuvastatin is effective at lowering LDL and poses a low risk for drug-drug interaction as it does not share the same metabolic pathway as HAART drugs. This study sought to determine the efficacy of rosuvastatin on lipid parameters in HIV positive patients with HIV metabolic syndrome.ResultsMean TC decreased from 6.54 to 4.89 mmol/L (25.0% reduction, p < 0.001). Mean LDL-C decreased from 3.39 to 2.24 mmol/L (30.8% reduction, p < 0.001). Mean HDL rose from 1.04 to 1.06 mmol/L (2.0% increase, p = ns). Mean triglycerides decreased from 5.26 to 3.68 mmol/L (30.1% reduction, p < 0.001). Secondary analysis examining the effectiveness of rosuvastatin monotherapy (n = 70) vs. rosuvastatin plus fenofibrate (n = 43) showed an improvement of 21.3% in TG and a decrease of 4.1% in HDL-C in the monotherapy group. The rosuvastatin plus fenofibrate showed a greater drop in triglycerides (45.3%, p < 0.001) and an increase in HDL of 7.6% (p = 0.08).ConclusionThis study found that rosuvastatin is effective at improving potentially atherogenic lipid parameters in HIV-positive patients. The lipid changes we observed were of a smaller magnitude compared to non-HIV subjects. Our results are further supported by a small, pilot trial examining rosuvastatin effectiveness in HIV who reported similar median changes from baseline of -21.7% (TC), -22.4% (LDL-C), -30.1% (TG) with the exception of a 28.5% median increase in HDL. In light of the results revealed by this pilot study, clinicians may want to consider a possible resistance to statin therapy when treating patients with HIV metabolic syndrome.

Rosuvastatin: The Most Efficient Treatment Option For Patients With Dyslipidemia

It has been unequivocally proven that lowering serum cholesterol reduces the risk of cardiovascular disease. For every 1% reduction in serum total cholesterol, the risk of coronary heart disease is lowered by 2%, and with a 1 mmol/l reduction in low-density lipoprotein cholesterol (LDL-C), the 5-year incidence of major coronary events, coronary revascularization and stroke, is reduced by approximately one fifth. The risk of cardiovascular disease increases linearly with increasing serum cholesterol. Thus, people with high cholesterol levels have the highest risk, but in any population the largest number of cardiovascular events and deaths will occur in people whose serum cholesterol is only marginally elevated, as they form the largest pool of the background population. Unfortunately, a significant number of patients requiring lipid-modifying therapy remain untreated or suboptimally treated, with almost half failing to reach current guideline targets for LDL-C, and therefore remaining at unacceptably high risk of a cardiovascular event, such as a myocardial infarction or stroke, despite receiving medical treatment. This is partly due to noncompliance or ineffective use of cholesterol-lowering therapy. Consequently, there remains a need for an effective, well-tolerated agent or combination of such agents that can produce beneficial changes in the atherogenic lipid profile and enable the majority of patients requiring lipid-lowering therapy to reach their recommended LDL-C goals. Among the statins, rosuvastatin monotherapy has been shown to have superior efficacy in reducing LDL-C across its licensed dose range. At daily doses of 5–40 mg, rosuvastatin produces mean reductions in plasma LDL-C of 45–63%, achieves LDL-C goals in 48–89% of patients, and is more effective than equivalent and maximum doses of atorvastatin, simvastatin and pravastatin. This means that fewer patients treated with rosuvastatin will require other cholesterol-lowering agents, leading to lower treatment cost. Rosuvastatin also improves high-density lipoprotein cholesterol (HDL-C), triglyceride and lipid ratios, such as LDL-C:HDL-C ratio. Furthermore, a recent study showed that significant regression of atherosclerosis can be achieved with intensive statin therapy using rosuvastatin 40 mg. The safety and tolerability of rosuvastatin is similar to other marketed statins. Rosuvastatin as a single therapy is a valuable option and, thus far, the most efficient treatment for a broad spectrum of patients with dyslipidemia. In particular, the overall lipid profile, including HDL-C and triglycerides, in patients with Type 2 diabetes or the metabolic syndrome is markedly improved with rosuvastatin therapy.

Rosuvastatin for the Treatment of Hypercholesterolemia

Rosuvastatin, a new hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), is approved as an adjunct to diet in patients with primary hypercholesterolemia, mixed dyslipidemia, or Fredrickson type IV hypercholesterolemia. Because of its increased affinity for the reductase, rosuvastatin reduces the low-density lipoprotein cholesterol (LDL) level more than atorvastatin, simvastatin, and pravastatin do, without additional adverse effects. In addition, cytochrome P450 isoenzymes do not extensively metabolize rosuvastatin, and inhibitors of these isoenzymes do not substantially affect it. Rosuvastatin could be a first-line option for patients requiring a reduction of 50% or more to reach the LDL goal of the National Cholesterol Education Program Adult Treatment Panel III. Rosuvastatin monotherapy may allow patients to achieve this LDL goal earlier, and it may help them avoid combination therapy or potential adverse effects of high-dose statin therapy. However, because cardiovascular disease morbidity and mortality data are lacking for rosuvastatin (but available for all other marketed statins) and because its postmarketing data are limited, rosuvastatin should be reserved for patients requiring an LDL reduction of 50% or less who cannot reach the recommended goal with other statins because of adverse effects, drug interactions, or cost.

Rosuvastatin Alone or With Extended‐Release Niacin: A New Therapeutic Option for Patients With Combined Hyperlipidemia

Combination therapy with a statin and niacin may provide optimal therapy for patients with combined hyperlipidemia and low levels of high-density lipoprotein (HDL) cholesterol. The authors assessed the efficacy and safety of rosuvastatin monotherapy, extended-release (ER) niacin monotherapy, or rosuvastatin and ER niacin combined therapy in patients with atherogenic dyslipidemia. In a 24-week, open-label, multicenter trial, men and women aged > or =18 years with fasting levels of total cholesterol > or =200 mg/dL, HDL cholesterol > or =45 mg/dL, triglycerides 200-800 mg/dL, and apolipoprotein B > or =110 mg/dL were randomly assigned to one of four treatment groups: rosuvastatin 10-40 mg, ER niacin 0.5-2 g, rosuvastatin 40 mg plus ER niacin 0.5-1 g, or rosuvastatin 10 mg plus ER niacin 0.5-2 g. Daily doses of rosuvastatin 40 mg monotherapy reduced low-density lipoprotein (LDL) cholesterol and non-HDL cholesterol levels significantly more than did either ER niacin 2 g monotherapy or rosuvastatin 10 mg combined with ER niacin 2 g. Addition of ER niacin 1 g to rosuvastatin 40 mg did not further reduce total or non-HDL cholesterol. Triglyceride reductions were similar among the four treatment groups. ER niacin mono- and combined therapy produced significantly greater rises in HDL cholesterol and apolipoprotein A-1 than did rosuvastatin monotherapy. Rosuvastatin monotherapy was better tolerated than ER niacin taken either alone or with rosuvastatin. In this study, rosuvastatin very effectively improved the three major lipoprotein-lipid abnormalities of combined hyperlipidemia.

Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels

Patients with combined hyperlipidemia and low high-density lipoprotein (HDL) cholesterol levels may benefit from combination therapy with a statin and niacin; therefore, we assessed the efficacy and safety of rosuvastatin and extended-release (ER) niacin alone and in combination in 270 patients with this atherogenic dyslipidemia. Men and women ≥18 years with fasting total cholesterol levels ≥200 mg/dl, triglycerides 200 to 800 mg/dl, apolipoprotein B ≥110 mg/dl, and HDL cholesterol <45 mg/dl were randomized to 1 of 4 treatments in this 24-week, open-label, multicenter trial: rosuvastatin 10 to 40 mg; ER niacin 0.5 to 2 g; rosuvastatin 40 mg/ER niacin 0.5 to 1 g; or rosuvastatin 10 mg/ER niacin 0.5 to 2 g. Percent changes from baseline in low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and other lipid measurements at week 24 were determined by analysis of variance, with statistical testing performed separately between the rosuvastatin monotherapy group and each remaining treatment group. Daily doses of rosuvastatin 40 mg reduced LDL and non-HDL cholesterol significantly more than either ER niacin 2 g or rosuvastatin 10 mg/ER niacin 2 g (−48% vs −0.1% and −36% for LDL cholesterol and −49% vs −11% and −38% for non-HDL cholesterol, respectively; p <0.01 for all comparisons); no additional reduction in LDL or non-HDL cholesterol was observed with the combination of rosuvastatin 40 mg/ER niacin 1.0 g (−42% and −47%; p = NS). Triglyceride reductions ranged from −21% (ER niacin monotherapy) to −39% (rosuvastatin 40 mg/ER niacin 1 g), but no observed differences were statistically significant. Compared with rosuvastatin alone, rosuvastatin 10 mg/ER niacin 2 g produced significantly greater increases in HDL cholesterol (11% vs 24%, p <0.001) and apolipoprotein A-I (5% vs 11%, p <0.017). Similar increases in HDL cholesterol and apolipoprotein A-I were noted between the monotherapy groups. Over 24 weeks, rosuvastatin alone was better tolerated than either ER niacin alone or the combinations of rosuvastatin and ER niacin.