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| | #redirect [[Lovastatin#Clinical Studies]] |
| {{Lovastatin}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Clinical Studies==
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| ===[[hypercholesterolemia]]===
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| Altoprev® has been shown to reduce Total-C, LDL-C, and TG and increase [[HDL-C]] in patients with [[hypercholesterolemia]]. Near maximal response was observed after four weeks of treatment and the response was maintained with continuation of therapy for up to 6 months.
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| In a 12-week, multicenter, placebo-controlled, double-blind, dose-response study in adult men and women 21 to 70 years of age with primary [[hypercholesterolemia]], once daily administration of Altoprev® 10 to 60 mg in the evening was compared to placebo. Altoprev® produced dose related reductions in LDL-C and Total-C. Altoprev®produced mean reductions in TG across all doses that varied from approximately 10% to 25%. Altoprev® produced mean increases in [[HDL-C]] across all doses that varied from approximately 9% to 13%.
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| The lipid changes with Altoprev® treatment in this study, from baseline to endpoint, are displayed in Table 6.
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| {|
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| |[[File:Lovastatin08.jpg|thumb|800px]]
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| N= the number of patients with values at both baseline and endpoint.
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| *Except for the [[HDL-C]] elevation with Altoprev® 10 mg, all lipid changes with
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| Altoprev® were statistically significant compared to placebo.
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| **For LDL-C, 33 patients had values at baseline and endpoint.
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| The range of LDL-C responses is represented graphically in the following figure (Figure 2):
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| {|
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| |[[File:Lovastatin09.jpg|thumb|800px]]
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| The distribution of LDL-C responses is represented graphically by the boxplots in Figure 2. The bottom line of the box represents the 25th percentile and the top line, the 75th percentile. The horizontal line in the box represents the median and the gray area is the 95% confidence interval for the median. The range of responses is depicted by the tails and outliers.
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| Expanded Clinical Evaluation of Lovastatin (EXCEL) Study
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| Lovastatin immediate-release was compared to placebo in 8,245 patients with [[hypercholesterolemia]] [Total-C 240-300mg/dL (6.2 mmol/L-7.6 mmol/L), LDL-C >160 mg/dL (4.1 mmol/L)] in the randomized, double-blind, parallel, 48-week EXCEL study. All changes in the lipid measurements (see Table 7) observed in lovastatin immediate-release-treated patients were dose-related and significantly different from placebo (p≤0.001). These results were sustained throughout the study.
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| {|
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| |[[File:Lovastatin10.jpg|thumb|800px]]
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| ====Altoprev® Long-Term Study====
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| A total of 365 patients were enrolled in an extension study in which all patients were administered Altoprev® 40 mg or 60 mg once daily for up to 6 months of treatment. The lipid-altering effects of Altoprev® were comparable to what was observed in the dose-response study, and were maintained for up to 6 months of treatment.
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| Specific Populations
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| In clinical studies with Altoprev®, there were no statistically significant differences in LDL-C reduction in an older population (≥65 years old), compared to a younger population (<65 years old). There were also no statistically significant differences in LDL-C reduction between male and female patients.
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| ===Heterozygous Familial [[hypercholesterolemia]]===
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| Lovastatin Immediate-Release
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| Lovastatin immediate-release has been shown to be effective in reducing Total-C and LDL-C in heterozygous familial and non-familial forms of primary [[hypercholesterolemia]] and in mixed [[hyperlipidemia]]. A marked response was seen within 2 weeks, and the maximum therapeutic response occurred within 4-6 weeks. The response was maintained during continuation of therapy. Single daily doses given in the evening were more effective than the same dose given in the morning, perhaps because [[cholesterol]] is synthesized mainly at night.
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| Lovastatin immediate-release was studied in controlled trials in hypercholesterolemic patients with well-controlled non-insulin dependent [[diabetes mellitus]] with normal renal function. The effect of lovastatin immediate-release on lipids and lipoproteins and the safety profile of lovastatin immediate-release were similar to that demonstrated in studies in nondiabetics. Lovastatin immediate-release had no clinically important effect on glycemic control or on the dose requirement of oral hypoglycemic agents.
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| ===Prevention of Coronary Heart Disease===
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| The Air Force/Texas Coronary [[Atherosclerosis]] Prevention Study (AFCAPS/TexCAPS), a double-blind, randomized, placebo-controlled, primary prevention study, demonstrated that treatment with lovastatin immediate-release decreased the rate of acute major coronary events (composite endpoint of myocardial infarction, unstable angina, and sudden cardiac death) compared with placebo during a median of 5.1 years of follow-up. Participants were middle-aged and elderly men (ages 45-73) and women (ages 55-73) without symptomatic cardiovascular disease with average to moderately elevated Total-C and LDL-C, below average [[HDL-C]], and who were at high risk based on elevated Total-C/[[HDL-C]]. In addition to age, 63% of the participants had at least one other risk factor (baseline [[HDL-C]] <35 mg/dL, [[hypertension]], family history, smoking and diabetes).
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| AFCAPS/TexCAPS enrolled 6,605 participants (5,608 men, 997 women) based on the following lipid entry criteria: Total-C range of 180-264 mg/dL, LDL-C range of 130-190 mg/dL, [[HDL-C]] of ≤45 mg/dL for men and ≤47 mg/dL for women, and TG of ≤400 mg/dL. Participants were treated with standard care, including diet, and either lovastatin immediate-release 20 mg - 40 mg daily (n= 3,304) or placebo (n= 3,301). Approximately 50% of the participants treated with lovastatin immediate-release were titrated to 40 mg daily when their LDL-C remained >110 mg/dL at the 20-mg starting dose.
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| Lovastatin immediate-release reduced the risk of a first acute major coronary event, the primary efficacy endpoint, by 37% (lovastatin immediate-release 3.5%, placebo 5.5%; p<0.001; Figure 3). A first acute major coronary event was defined as myocardial infarction (54 participants on lovastatin immediate-release, 94 on placebo) or unstable angina (54 vs. 80) or sudden cardiac death (8 vs. 9). Furthermore, among the secondary endpoints, lovastatin immediate-release reduced the risk of [[unstable angina]] by 32% (1.8% vs. 2.6%; p=0.023), of [[myocardial infarction]] by 40% (1.7% vs. 2.9%; p=0.002), and of undergoing coronary revascularization procedures (e.g., [[coronary artery bypass grafting]] or [[percutaneous transluminal coronary angioplasty]]) by 33% (3.2% vs. 4.8%; p=0.001). Trends in risk reduction associated with treatment with lovastatin immediate-release were consistent across men and women, smokers and non-smokers, hypertensives and non-hypertensives, and older and younger participants. Participants with ≥2 risk factors had risk reductions (RR) in both acute major coronary events (RR 43%) and coronary revascularization procedures (RR 37%). Because there were too few events among those participants with age as their only risk factor in this study, the effect of lovastatin immediate-release on outcomes could not be adequately assessed in this subgroup.
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| {|
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| |[[File:Lovastatin11.jpg|thumb|800px]]
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| ====[[Atherosclerosis]]====
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| In the Canadian Coronary [[Atherosclerosis]] Intervention Trial (CCAIT), the effect of therapy with lovastatin on coronary [[Atherosclerosis]] was assessed by coronary angiography in hyperlipidemic patients. In this randomized, double-blind, controlled clinical trial, patients were treated with conventional measures (usually diet and 325 mg of aspirin every other day) and either lovastatin 20 mg - 80 mg daily or placebo. Angiograms were evaluated at baseline and at two years by computerized quantitative coronary angiography (QCA). Lovastatin significantly slowed the progression of lesions as measured by the mean change per-patient in minimum lumen diameter (the primary endpoint) and percent diameter stenosis, and decreased the proportions of patients categorized with disease progression (33% vs. 50%) and with new lesions (16% vs. 32%).
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| In a similarly designed trial, the Monitored [[Atherosclerosis]] Regression Study (MARS), patients were treated with diet and either lovastatin 80 mg daily or placebo. No statistically significant difference between lovastatin and placebo was seen for the primary endpoint (mean change per patient in percent diameter stenosis of all lesions), or for most secondary QCA endpoints. Visual assessment by angiographers who formed a consensus opinion of overall angiographic change (Global Change Score) was also a secondary endpoint. By this endpoint, significant slowing of disease was seen, with regression in 23% of patients treated with lovastatin compared to 11% of placebo patients.
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| The effect of lovastatin on the progression of [[Atherosclerosis]] in the coronary arteries has been corroborated by similar findings in another vasculature. In the Asymptomatic Carotid Artery Progression Study (ACAPS), the effect of therapy with lovastatin on carotid [[Atherosclerosis]] was assessed by B-mode ultrasonography in hyperlipidemic patients with early carotid lesions and without known coronary heart disease at baseline. In this double- blind, controlled clinical trial, 919 patients were randomized in a 2 x 2 factorial design to placebo, lovastatin 10-40 mg daily and/or [[warfarin]]. Ultrasonograms of the carotid walls were used to determine the change per patient from baseline to three years in mean maximum intimal-medial thickness (IMT) of 12 measured segments. There was a significant regression of carotid lesions in patients receiving lovastatin alone compared to those receiving placebo alone (p=0.001). The predictive value of changes in IMT for stroke has not yet been established. In the lovastatin group there was a significant reduction in the number of patients with major cardiovascular events relative to the placebo group (5 vs. 14) and a significant reduction in all-cause mortality (1 vs. 8).
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| ====Eye====
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| There was a high prevalence of baseline lenticular opacities in the patient population included in the early clinical trials with lovastatin immediate-release. During these trials the appearance of new opacities was noted in both the lovastatin immediate-release and placebo groups. There was no clinically significant change in visual acuity in the patients who had new opacities reported nor was any patient, including those with opacities noted at baseline, discontinued from therapy because of a decrease in visual acuity.
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| A three-year, double-blind, placebo-controlled study in hypercholesterolemic patients to assess the effect of lovastatin immediate-release on the human lens demonstrated that there were no clinically or statistically significant differences between the lovastatin immediate-release and placebo groups in the incidence, type or progression of lenticular opacities. There are no controlled clinical data assessing the lens available for treatment beyond three years.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = ALTOPREV (LOVASTATIN) TABLET, EXTENDED RELEASE [SHIONOGI INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e8b6ccc2-e6e7-45fd-ab66-c312bcbe2b01 | publisher = | date = | accessdate = 13 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:Statins]] |
| [[Category:Carboxylate esters]] | | [[Category:Carboxylate esters]] |
| [[Category:Lactones]] | | [[Category:Lactones]] |
| [[Category:Cardiovascular Drug]] | | [[Category:Cardiovascular Drugs]] |
| [[Category:Drug]] | | [[Category:Drug]] |