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| __NOTOC__
| | #REDIRECT [[Rosuvastatin#Clinical Studies]] |
| {{Rosuvastatin}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Clinical Studies==
| | [[Category: Cardiovascular Drugs]] |
| | | [[Category: Drug]] |
| ===hyperlipidemia and Mixed Dyslipidemia===
| | [[Category: Statins]] |
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| CRESTOR reduces Total‑C, LDL‑C, ApoB, nonHDL‑C, and TG, and increases HDL‑C, in adult patients with [hyperlipidemia]] and mixed [[dyslipidemia]].
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| '''Dose-Ranging Study''': In a multicenter, double-blind, placebo-controlled, dose-ranging study in patients with [hyperlipidemia]] CRESTOR given as a single daily dose for 6 weeks significantly reduced Total‑C, LDL‑C, nonHDL‑C, and ApoB, across the dose range (Table 6).
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| |[[File:Rosuvastatin08.jpg|thumb|800px]]
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| Active-Controlled Study: CRESTOR was compared with the HMG‑CoA reductase inhibitors [[atorvastatin]], [[simvastatin]], and [[pravastatin]] in a multicenter, open-label, dose-ranging study of 2240 patients with [[hyperlipidemia]] or mixed dyslipidemia. After randomization, patients were treated for 6 weeks with a single daily dose of either CRESTOR, atorvastatin, simvastatin, or pravastatin (Figure 1 and Table 7).
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| Figure 1. Percent LDL‑ C Change by Dose of CRESTOR, [[Atorvastatin]], [[Simvastatin]], and [[Pravastatin]] at Week 6 in Patients with [hyperlipidemia]] or Mixed [[Dyslipidemia]]
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| |[[File:Rosuvastatin09.jpg|thumb|800px]]
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| Box plots are a representation of the 25th, 50th, and 75th percentile values, with whiskers representing the 10th and 90th percentile values. Mean baseline LDL‑C: 189 mg/dL
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| ===Heterozygous Familial Hypercholesterolemia===
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| Active-Controlled Study: In a study of patients with heterozygous FH (baseline mean LDL of 291), patients were randomized to CRESTOR 20 mg or atorvastatin 20 mg. The dose was increased by 6-week intervals. Significant LDL-C reductions from baseline were seen at each dose in both treatment groups (Table 8).
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| ===Hypertriglyceridemia===
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| Dose-Response Study: In a double-blind, placebo-controlled dose-response study in patients with baseline TG levels from 273 to 817 mg/dL, CRESTOR given as a single daily dose (5 to 40 mg) over 6 weeks significantly reduced serum TG levels (Table 9).
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| {|
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| ===Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia)===
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| In a randomized, multicenter, double-blind crossover study, 32 patients (27 with є2/є2 and 4 with apo E mutation [Arg145Cys] with primary [[dysbetalipoproteinemia]] (Type III [[Hyperlipoproteinemia]]) entered a 6-week dietary lead-in period on the NCEP Therapeutic Lifestyle Change (TLC) diet. Following dietary lead-in, patients were randomized to a sequence of treatments in conjunction with the TLC diet for 6 weeks each: rosuvastatin 10 mg followed by rosuvastatin 20 mg or rosuvastatin 20 mg followed by rosuvastatin 10 mg. CRESTOR reduced nonHDL‑C (primary end point) and circulating remnant lipoprotein levels. Results are shown in the table below.
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| <font color="#777777">===</font>Homozygous Familial Hypercholesterolemia===
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| Dose-Titration Study: In an open-label, forced-titration study, homozygous FH patients (n=40, 8‑63 years) were evaluated for their response to CRESTOR 20 to 40 mg titrated at a 6‑week interval. In the overall population, the mean LDL‑C reduction from baseline was 22%. About one-third of the patients benefited from increasing their dose from 20 mg to 40 mg with further LDL lowering of greater than 6%. In the 27 patients with at least a 15% reduction in LDL‑C, the mean LDL-C reduction was 30% (median 28% reduction). Among 13 patients with an LDL‑C reduction of <15%, 3 had no change or an increase in LDL‑C. Reductions in LDL‑C of 15% or greater were observed in 3 of 5 patients with known receptor negative status.
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| ===Pediatric Patients with Heterozygous Familial Hypercholesterolemia===
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| In a double blind, randomized, multicenter, placebo-controlled, 12 week study, 176 (97 male and 79 female) children and adolescents with heterozygous familial [[Hypercholesterolemia]] were randomized to rosuvastatin 5, 10 or 20 mg or placebo daily. Patients ranged in age from 10 to 17 years (median age of 14 years) with approximately 30% of the patients 10 to 13 years and approximately 17%, 18%, 40%, and 25% at Tanner stages II, III, IV, and V, respectively. Females were at least 1 year postmenarche. Mean LDL C at baseline was 233 mg/dL (range of 129 to 399). The 12 week double blind phase was followed by a 40 week open label dose-titration phase, where all patients (n=173) received 5 mg, 10 mg or 20 mg rosuvastatin daily.
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| Rosuvastatin significantly reduced LDL-C (primary end point), total [[cholesterol]] and ApoB levels at each dose compared to placebo. Results are shown in Table 11 below.
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| At the end of the 12 week, double blind treatment period, the percentage of patients achieving the LDL C goal of less than 110 mg/dL (2.8 mmol/L) was 0% for placebo, 12% for rosuvastatin 5 mg, 41% for rosuvastatin 10 mg and 41% for rosuvastatin 20 mg. For the 40 week, open label phase, 71% of the patients were titrated to the maximum dose of 20 mg and 41% of the patients achieved the LDL C goal of 110 mg/dL.
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| The long-term efficacy of rosuvastatin therapy initiated in childhood to reduce morbidity and mortality in adulthood has not been established.
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| ===Slowing of the Progression of [[atherosclerosis]]===
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| In the Measuring Effects on Intima Media Thickness: an Evaluation Of Rosuvastatin 40 mg (METEOR) study, the effect of therapy with CRESTOR on carotid [[atherosclerosis]] was assessed by B-mode ultrasonography in patients with elevated LDL‑C, at low risk (Framingham risk <10% over ten years) for symptomatic coronary artery disease and with subclinical [[atherosclerosis]] as evidenced by carotid intimal-medial thickness (cIMT). In this double-blind, placebo-controlled clinical study 984 patients were randomized (of whom 876 were analyzed) in a 5:2 ratio to CRESTOR 40 mg or placebo once daily. Ultrasonograms of the carotid walls were used to determine the annualized rate of change per patient from baseline to two years in mean maximum cIMT of 12 measured segments. The estimated difference in the rate of change in the maximum cIMT analyzed over all 12 carotid artery sites between patients treated with CRESTOR and placebo-treated patients was -0.0145 mm/year (95% CI –0.0196, –0.0093; p<0.0001).
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| The annualized rate of change from baseline for the placebo group was +0.0131 mm/year (p<0.0001). The annualized rate of change from baseline for the group treated with CRESTOR was -0.0014 mm/year (p=0.32).
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| At an individual patient level in the group treated with CRESTOR, 52.1% of patients demonstrated an absence of disease progression (defined as a negative annualized rate of change), compared to 37.7% of patients in the placebo group.
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| ===Primary Prevention of Cardiovascular Disease===
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| In the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, the effect of CRESTOR (rosuvastatin calcium) on the occurrence of major cardiovascular (CV) disease events was assessed in 17,802 men (≥50 years) and women (≥60 years) who had no clinically evident [[cardiovascular disease]], LDL‑C levels <130 mg/dL (3.3 mmol/l) and hs‑CRP levels ≥2 mg/L. The study population had an estimated baseline coronary heart disease risk of 11.6% over 10 years based on the Framingham risk criteria and included a high percentage of patients with additional risk factors such as [[hypertension]] (58%), low HDL‑C levels (23%), cigarette smoking (16%), or a family history of premature CHD (12%). Study participants had a median baseline LDL‑C of 108 mg/dL and hsCRP of 4.3 mg/L. Study participants were randomly assigned to placebo (n=8901) or rosuvastatin 20 mg once daily (n=8901) and were followed for a mean duration of 2 years. The JUPITER study was stopped early by the Data Safety Monitoring Board due to meeting predefined stopping rules for efficacy in rosuvastatin-treated subjects.
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| The primary end point was a composite end point consisting of the time-to-first occurrence of any of the following major CV events: CV death, nonfatal [[myocardial infarction]], nonfatal stroke, [[hospitalization]] for [[unstable angina]] or an arterial [[revascularization]] procedure.
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| Rosuvastatin significantly reduced the risk of major CV events (252 events in the placebo group vs. 142 events in the rosuvastatin group) with a statistically significant (p<0.001) relative risk reduction of 44% and absolute risk reduction of 1.2% (see Figure 2). The risk reduction for the primary end point was consistent across the following predefined subgroups: age, sex, race, smoking status, family history of premature CHD, body mass index, LDL‑C, HDL‑C, and hsCRP levels.
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| Figure 2. Time to first occurrence of major cardiovascular events in JUPITER
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| {|
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| The individual components of the primary end point are presented in Figure 3. Rosuvastatin significantly reduced the risk of nonfatal myocardial infarction, nonfatal stroke, and arterial [[revascularization]] procedures. There were no significant treatment differences between the rosuvastatin and placebo groups for death due to cardiovascular causes or hospitalizations for [[unstable angina]].
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| Rosuvastatin significantly reduced the risk of myocardial infarction (6 fatal events and 62 nonfatal events in placebo-treated subjects vs. 9 fatal events and 22 nonfatal events in rosuvastatin-treated subjects) and the risk of stroke (6 fatal events and 58 nonfatal events in placebo-treated subjects vs. 3 fatal events and 30 nonfatal events in rosuvastatin-treated subjects).
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| In a post-hoc subgroup analysis of JUPITER subjects (n=1405; rosuvastatin=725, placebo=680) with a hsCRP ≥2 mg/L and no other traditional risk factors (smoking, BP ≥140/90 or taking [[antihypertensives]], low HDL‑C) other than age, after adjustment for high HDL‑C, there was no significant treatment benefit with rosuvastatin treatment.
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| {|
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| At one year, rosuvastatin increased HDL‑C and reduced LDL‑C, hsCRP, total [[cholesterol]] and serum [[triglyceride]] levels (p<0.001 for all versus placebo).<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = CRESTOR (ROSUVASTATIN CALCIUM) TABLET, FILM COATED [ASTRAZENECA PHARMACEUTICALS LP] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=bb0f3b5e-4bc6-41c9-66b9-6257e2513512 | publisher = | date = | accessdate = 17 February 2014 }}</ref>
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| ==References==
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| {{Reflist|2}}
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| {{Statins}}
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| [[Category:Statins]] | |
| [[Category:AstraZeneca]]
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| [[Category:Carboxylic acids]]
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| [[Category:Sulfonamides]]
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| [[Category:Pyrimidines]]
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| [[Category:Organofluorides]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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