Mevacor1 (Lovastatin) is a cholesterol lowering agent isolated from a strain of Aspergillus terreus. After oral ingestion, lovastatin, which is an inactive lactone, is hydrolyzed to the corresponding β‑hydroxyacid form. This is a principal metabolite and an inhibitor of 3‑hydroxy-3‑methylglutaryl-coenzyme A (HMG‑CoA) reductase. This enzyme catalyzes the conversion of HMG‑CoA to mevalonate, which is an early and rate limiting step in the biosynthesis of cholesterol.
Lovastatin is [1S -[1α(R*),3α,7β,8β(2S*,4S*), 8aβ]]-1,2,3,7, 8,8a‑hexahydro - 3,7‑dimethyl - 8 - [2‑(tetrahydro - 4 - hydroxy - 6 - oxo - 2H - pyran - 2‑yl)ethyl] - 1 - naphthalenyl 2 - methylbutanoate. The empirical formula of lovastatin is C24H36O5 and its molecular weight is 404.55. Its structural formula is:
Lovastatin is a white, nonhygroscopic crystalline powder that is insoluble in water and sparingly soluble in ethanol, methanol, and acetonitrile.
Tablets Mevacor are supplied as 20 mg and 40 mg tablets for oral administration. In addition to the active ingredient lovastatin, each tablet contains the following inactive ingredients: cellulose, lactose, magnesium stearate, and starch. Butylated hydroxyanisole (BHA) is added as a preservative. Tablets Mevacor 20 mg also contain FD&C Blue 2 aluminum lake. Tablets Mevacor 40 mg also contain D&C Yellow 10 aluminum lake and FD&C Blue 2 aluminum lake.
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Registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Copyright © 1987-2007 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
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Mevacor - Clinical Pharmacology
The involvement of low-density lipoprotein cholesterol (LDL‑C) in atherogenesis has been well-documented in clinical and pathological studies, as well as in many animal experiments. Epidemiological and clinical studies have established that high LDL‑C and low high-density lipoprotein cholesterol (HDL‑C) are both associated with coronary heart disease. However, the risk of developing coronary heart disease is continuous and graded over the range of cholesterol levels and many coronary events do occur in patients with total cholesterol (total‑C) and LDL‑C in the lower end of this range.
Mevacor has been shown to reduce both normal and elevated LDL‑C concentrations. LDL is formed from very low-density lipoprotein (VLDL) and is catabolized predominantly by the high affinity LDL receptor. The mechanism of the LDL-lowering effect of Mevacor may involve both reduction of VLDL‑C concentration, and induction of the LDL receptor, leading to reduced production and/or increased catabolism of LDL‑C. Apolipoprotein B also falls substantially during treatment with Mevacor. Since each LDL particle contains one molecule of apolipoprotein B, and since little apolipoprotein B is found in other lipoproteins, this strongly suggests that Mevacor does not merely cause cholesterol to be lost from LDL, but also reduces the concentration of circulating LDL particles. In addition, Mevacor can produce increases of variable magnitude in HDL‑C, and modestly reduces VLDL‑C and plasma triglycerides (TG) (see Tables I-III under Clinical Studies). The effects of Mevacor on Lp(a), fibrinogen, and certain other independent biochemical risk markers for coronary heart disease are unknown.
Mevacor is a specific inhibitor of HMG‑CoA reductase, the enzyme which catalyzes the conversion of HMG‑CoA to mevalonate. The conversion of HMG‑CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol.
Pharmacokinetics
Lovastatin is a lactone which is readily hydrolyzed in vivo to the corresponding β‑hydroxyacid, a potent inhibitor of HMG‑CoA reductase. Inhibition of HMG‑CoA reductase is the basis for an assay in pharmacokinetic studies of the β‑hydroxyacid metabolites (active inhibitors) and, following base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of lovastatin.
Following an oral dose of 14C‑labeled lovastatin in man, 10% of the dose was excreted in urine and 83% in feces. The latter represents absorbed drug equivalents excreted in bile, as well as any unabsorbed drug. Plasma concentrations of total radioactivity (lovastatin plus 14C‑metabolites) peaked at 2 hours and declined rapidly to about 10% of peak by 24 hours postdose. Absorption of lovastatin, estimated relative to an intravenous reference dose, in each of four animal species tested, averaged about 30% of an oral dose. In animal studies, after oral dosing, lovastatin had high selectivity for the liver, where it achieved substantially higher concentrations than in non-target tissues. Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. As a consequence of extensive hepatic extraction of lovastatin, the availability of drug to the general circulation is low and variable. In a single dose study in four hypercholesterolemic patients, it was estimated that less than 5% of an oral dose of lovastatin reaches the general circulation as active inhibitors. Following administration of lovastatin tablets the coefficient of variation, based on between-subject variability, was approximately 40% for the area under the curve (AUC) of total inhibitory activity in the general circulation.
Both lovastatin and its β‑hydroxyacid metabolite are highly bound (>95%) to human plasma proteins. Animal studies demonstrated that lovastatin crosses the blood-brain and placental barriers.
The major active metabolites present in human plasma are the β‑hydroxyacid of lovastatin, its 6´‑hydroxy derivative, and two additional metabolites. Peak plasma concentrations of both active and total inhibitors were attained within 2 to 4 hours of dose administration. While the recommended therapeutic dose range is 10 to 80 mg/day, linearity of inhibitory activity in the general circulation was established by a single dose study employing lovastatin tablet dosages from 60 to as high as 120 mg. With a once-a-day dosing regimen, plasma concentrations of total inhibitors over a dosing interval achieved a steady state between the second and third days of therapy and were about 1.5 times those following a single dose. When lovastatin was given under fasting conditions, plasma concentrations of total inhibitors were on average about two-thirds those found when lovastatin was administered immediately after a standard test meal.
In a study of patients with severe renal insufficiency (creatinine clearance 10–30 mL/min), the plasma concentrations of total inhibitors after a single dose of lovastatin were approximately two-fold higher than those in healthy volunteers.
In a study including 16 elderly patients between 70–78 years of age who received Mevacor 80 mg/day, the mean plasma level of HMG‑CoA reductase inhibitory activity was increased approximately 45% compared with 18 patients between 18–30 years of age (see PRECAUTIONS, Geriatric Use).
Although the mechanism is not fully understood, cyclosporine has been shown to increase the AUC of HMG-CoA reductase inhibitors. The increase in AUC for lovastatin and lovastatin acid is presumably due, in part, to inhibition of CYP3A4.
The risk of myopathy is increased by high levels of HMG‑CoA reductase inhibitory activity in plasma. Potent inhibitors of CYP3A4 can raise the plasma levels of HMG‑CoA reductase inhibitory activity and increase the risk of myopathy (see WARNINGS, Myopathy/Rhabdomyolysis and PRECAUTIONS, Drug Interactions).
Lovastatin is a substrate for cytochrome P450 isoform 3A4 (CYP3A4) (see PRECAUTIONS, Drug Interactions). Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma concentrations of drugs metabolized by CYP3A4. In one study2, 10 subjects consumed 200 mL of double-strength grapefruit juice (one can of frozen concentrate diluted with one rather than 3 cans of water) three times daily for 2 days and an additional 200 mL double-strength grapefruit juice together with and 30 and 90 minutes following a single dose of 80 mg lovastatin on the third day. This regimen of grapefruit juice resulted in a mean increase in the serum concentration of lovastatin and its β‑hydroxyacid metabolite (as measured by the area under the concentration-time curve) of 15‑fold and 5‑fold, respectively [as measured using a chemical assay— high performance liquid chromatography]. In a second study, 15 subjects consumed one 8 oz glass of single-strength grapefruit juice (one can of frozen concentrate diluted with 3 cans of water) with breakfast for 3 consecutive days and a single dose of 40 mg lovastatin in the evening of the third day. This regimen of grapefruit juice resulted in a mean increase in the plasma concentration (as measured by the area under the concentration-time curve) of active and total HMG‑CoA reductase inhibitory activity [using an enzyme inhibition assay both before (for active inhibitors) and after (for total inhibitors) base hydrolysis] of 1.34‑fold and 1.36‑fold, respectively, and of lovastatin and its β‑hydroxyacid metabolite [measured using a chemical assay — liquid chromatography/tandem mass spectrometry — different from that used in the first2 study] of 1.94‑fold and 1.57‑fold, respectively. The effect of amounts of grapefruit juice between those used in these two studies on lovastatin pharmacokinetics has not been studied.
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Kantola, T, et al., Clin Pharmacol Ther 1998; 63(4): 397–402.
Clinical Studies in Adults
Mevacor has been shown to be highly 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.
In multicenter, double-blind studies in patients with familial or non-familial hypercholesterolemia, Mevacor, administered in doses ranging from 10 mg q.p.m. to 40 mg b.i.d., was compared to placebo. Mevacor consistently and significantly decreased plasma total‑C, LDL‑C, total‑C/HDL‑C ratio and LDL‑C/HDL‑C ratio. In addition, Mevacor produced increases of variable magnitude in HDL‑C, and modestly decreased VLDL‑C and plasma TG (see Tables I through III for dose response results).
The results of a study in patients with primary hypercholesterolemia are presented in Table I.
| DOSAGE | N | TOTAL-C | LDL-C | HDL-C | LDL-C/ HDL-C | TOTAL-C/ HDL-C | TG. |
| Placebo | 33 | –2 | –1 | –1 | 0 | +1 | +9 |
Mevacor | |||||||
| 10 mg q.p.m. | 33 | –16 | –21 | +5 | –24 | –19 | –10 |
| 20 mg q.p.m. | 33 | –19 | –27 | +6 | –30 | –23 | +9 |
| 10 mg b.i.d. | 32 | –19 | –28 | +8 | –33 | –25 | –7 |
| 40 mg q.p.m. | 33 | –22 | –31 | +5 | –33 | –25 | –8 |
| 20 mg b.i.d. | 36 | –24 | –32 | +2 | –32 | –24 | –6 |
Mevacor was compared to cholestyramine in a randomized open parallel study. The study was performed with patients with hypercholesterolemia who were at high risk of myocardial infarction. Summary results are presented in Table II.
| TREATMENT | N | TOTAL-C (mean) | LDL-C (mean) | HDL-C (mean) | LDL-C/HDL-C (mean) | TOTAL-C/HDL-C (mean) | VLDL-C (median) | TG. (mean) |
| Mevacor | ||||||||
| 20 mg b.i.d. | 85 | –27 | –32 | +9 | –36 | –31 | –34 | –21 |
| 40 mg b.i.d. | 88 | –34 | –42 | +8 | –44 | –37 | –31 | –27 |
| Cholestyramine | ||||||||
| 12 g b.i.d. | 88 | –17 | –23 | +8 | –27 | –21 | +2 | +11 |
Mevacor was studied in controlled trials in hypercholesterolemic patients with well-controlled non-insulin dependent diabetes mellitus with normal renal function. The effect of Mevacor on lipids and lipoproteins and the safety profile of Mevacor were similar to that demonstrated in studies in nondiabetics. Mevacor had no clinically important effect on glycemic control or on the dose requirement of oral hypoglycemic agents.
Expanded Clinical Evaluation of Lovastatin (EXCEL) Study
Mevacor was compared to placebo in 8,245 patients with hypercholesterolemia (total-C 240-300 mg/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 (Table III) in Mevacor treated patients were dose-related and significantly different from placebo (p≤0.001). These results were sustained throughout the study.
| DOSAGE | N* | TOTAL-C (mean) | LDL-C (mean) | HDL-C (mean) | LDL-C/HDL-C (mean) | TOTAL-C/HDL-C (mean) | TG. (median) |
| |||||||
| Placebo | 1663 | +0.7 | +0.4 | +2.0 | +0.2 | +0.6 | +4 |
Mevacor | |||||||
| 20 mg q.p.m. | 1642 | –17 | –24 | +6.6 | –27 | –21 | –10 |
| 40 mg q.p.m. | 1645 | –22 | –30 | +7.2 | –34 | –26 | –14 |
| 20 mg b.i.d. | 1646 | –24 | –34 | +8.6 | –38 | –29 | –16 |
| 40 mg b.i.d. | 1649 | –29 | –40 | +9.5 | –44 | –34 | –19 |
The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), a double-blind, randomized, placebo-controlled, primary prevention study, demonstrated that treatment with Mevacor 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).
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 Mevacor 20-40 mg daily (n=3,304) or placebo (n=3,301). Approximately 50% of the participants treated with Mevacor were titrated to 40 mg daily when their LDL‑C remained >110 mg/dL at the 20‑mg starting dose.
Mevacor reduced the risk of a first acute major coronary event, the primary efficacy endpoint, by 37% (Mevacor 3.5%, placebo 5.5%; p<0.001; Figure 1). A first acute major coronary event was defined as myocardial infarction (54 participants on Mevacor, 94 on placebo) or unstable angina (54 vs. 80) or sudden cardiac death (8 vs. 9). Furthermore, among the secondary endpoints, Mevacor 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 Mevacor 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 Mevacor on outcomes could not be adequately assessed in this subgroup.
Figure 1: Acute Major Coronary Events (Primary Endpoint)
Atherosclerosis
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 the 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 20-80 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%).
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.
In the Familial Atherosclerosis Treatment Study (FATS), either lovastatin or niacin in combination with a bile acid sequestrant for 2.5 years in hyperlipidemic subjects significantly reduced the frequency of progression and increased the frequency of regression of coronary atherosclerotic lesions by QCA compared to diet and, in some cases, low-dose resin.
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).
Eye
There was a high prevalence of baseline lenticular opacities in the patient population included in the early clinical trials with lovastatin. During these trials the appearance of new opacities was noted in both the lovastatin 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.
A three‑year, double-blind, placebo-controlled study in hypercholesterolemic patients to assess the effect of lovastatin on the human lens demonstrated that there were no clinically or statistically significant differences between the lovastatin 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.
Clinical Studies in Adolescent Patients
Efficacy of Lovastatin in Adolescent Boys with Heterozygous Familial Hypercholesterolemia
In a double-blind, placebo-controlled study, 132 boys 10-17 years of age (mean age 12.7 yrs) with heterozygous familial hypercholesterolemia (heFH) were randomized to lovastatin (n=67) or placebo (n=65) for 48 weeks. Inclusion in the study required a baseline LDL‑C level between 189 and 500 mg/dL and at least one parent with an LDL‑C level >189 mg/dL. The mean baseline LDL‑C value was 253.1 mg/dL (range: 171-379 mg/dL) in the Mevacor group compared to 248.2 mg/dL (range: 158.5-413.5 mg/dL) in the placebo group. The dosage of lovastatin (once daily in the evening) was 10 mg for the first 8 weeks, 20 mg for the second 8 weeks, and 40 mg thereafter.
Mevacor significantly decreased plasma levels of total‑C, LDL‑C and apolipoprotein B (see Table IV).
| DOSAGE | N | TOTAL-C | LDL-C | HDL-C | TG.* | Apolipoprotein B |
| ||||||
| Placebo | 61 | –1.1 | –1.4 | –2.2 | –1.4 | –4.4 |
| Mevacor | 64 | –19.3 | –24.2 | +1.1 | –1.9 | –21 |
The mean achieved LDL‑C value was 190.9 mg/dL (range: 108-336 mg/dL) in the Mevacor group compared to 244.8 mg/dL (range: 135-404 mg/dL) in the placebo group.
Efficacy of Lovastatin in Post-Menarchal Girls with Heterozygous Familial Hypercholesterolemia
In a double-blind, placebo-controlled study, 54 girls 10-17 years of age who were at least 1 year post-menarche with heFH were randomized to lovastatin (n=35) or placebo (n=19) for 24 weeks. Inclusion in the study required a baseline LDL‑C level of 160-400 mg/dL and a parental history of familial hypercholesterolemia. The mean baseline LDL‑C value was 218.3 mg/dL (range: 136.3-363.7 mg/dL) in the Mevacor group compared to 198.8 mg/dL (range: 151.1-283.1 mg/dL) in the placebo group. The dosage of lovastatin (once daily in the evening) was 20 mg for the first 4 weeks, and 40 mg thereafter.
Mevacor significantly decreased plasma levels of total‑C, LDL‑C, and apolipoprotein B (see Table V).
| DOSAGE | N | TOTAL-C | LDL-C | HDL-C | TG.* | Apolipoprotein B |
| ||||||
| Placebo | 18 | +3.6 | +2.5 | +4.8 | –3.0 | +6.4 |
| Mevacor | 35 | –22.4 | –29.2 | +2.4 | –22.7 | –24.4 |
The mean achieved LDL‑C value was 154.5 mg/dL (range: 82-286 mg/dL) in the Mevacor group compared to 203.5 mg/dL (range: 135-304 mg/dL) in the placebo group.
The safety and efficacy of doses above 40 mg daily have not been studied in children. The long-term efficacy of lovastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.
Indications and Usage for Mevacor
Therapy with Mevacor should be a component of multiple risk factor intervention in those individuals with dyslipidemia at risk for atherosclerotic vascular disease. Mevacor should be used in addition to a diet restricted in saturated fat and cholesterol as part of a treatment strategy to lower total‑C and LDL‑C to target levels when the response to diet and other nonpharmacological measures alone has been inadequate to reduce risk.
Primary Prevention of Coronary Heart Disease
In individuals without symptomatic cardiovascular disease, average to moderately elevated total‑C and LDL‑C, and below average HDL‑C, Mevacor is indicated to reduce the risk of:
- Myocardial infarction
- Unstable angina
- Coronary revascularization procedures
(See CLINICAL PHARMACOLOGY, Clinical Studies.)
Coronary Heart Disease
Mevacor is indicated to slow the progression of coronary atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower total‑C and LDL‑C to target levels.
Hypercholesterolemia
Therapy with lipid-altering agents should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Mevacor is indicated as an adjunct to diet for the reduction of elevated total‑C and LDL‑C levels in patients with primary hypercholesterolemia (Types IIa and IIb3), when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate.
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Classification of Hyperlipoproteinemias
Lipoproteins Lipid Elevations Type elevated major minor IDL = intermediate-density lipoprotein. I chylomicrons TG ↑→C IIa LDL C — IIb LDL, VLDL C TG III (rare) IDL C/TG — IV VLDL TG ↑→C V (rare) chylomicrons, VLDL TG ↑→C
Mevacor is indicated as an adjunct to diet to reduce total‑C, LDL‑C and apolipoprotein B levels in adolescent boys and girls who are at least one year post-menarche, 10-17 years of age, with heFH if after an adequate trial of diet therapy the following findings are present:
- LDL-C remains >189 mg/dL or
- LDL-C remains >160 mg/dL and:
- there is a positive family history of premature cardiovascular disease or
- two or more other CVD risk factors are present in the adolescent patient
General Recommendations
Prior to initiating therapy with lovastatin, secondary causes for hypercholesterolemia (e.g., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded, and a lipid profile performed to measure total‑C, HDL‑C, and TG. For patients with TG less than 400 mg/dL (<4.5 mmol/L), LDL‑C can be estimated using the following equation:
LDL-C = total-C – [0.2 x (TG) + HDL-C]
For TG levels >400 mg/dL (>4.5 mmol/L), this equation is less accurate and LDL‑C concentrations should be determined by ultracentrifugation. In hypertriglyceridemic patients, LDL‑C may be low or normal despite elevated total‑C. In such cases, Mevacor is not indicated.
The National Cholesterol Education Program (NCEP) Treatment Guidelines are summarized below:
| Risk Category | LDL Goal (mg/dL) | LDL Level at Which to Initiate Therapeutic Lifestyle Changes (mg/dL) | LDL Level at Which to Consider Drug Therapy (mg/dL) |
| |||
| CHD* or CHD risk equivalents (10 year risk >20%) | <100 | ≥100 | ≥130 (100–129: drug optional)† |
| 2+ Risk factors (10-year risk ≤20%) | <130 | ≥130 | 10-year risk 10–20%: ≥130 10-year risk <10%: ≥ 160 |
| 0–1 Risk factor‡ | <160 | ≥160 | ≥190 (160–189: LDL-lowering drug optional) |
After the LDL‑C goal has been achieved, if the TG is still ≥200 mg/dL, non-HDL‑C (total‑C minus HDL‑C) becomes a secondary target of therapy. Non-HDL‑C goals are set 30 mg/dL higher than LDL‑C goals for each risk category.
At the time of hospitalization for an acute coronary event, consideration can be given to initiating drug therapy at discharge if the LDL‑C is ≥130 mg/dL (see NCEP Guidelines above).
Since the goal of treatment is to lower LDL‑C, the NCEP recommends that LDL‑C levels be used to initiate and assess treatment response. Only if LDL‑C levels are not available, should the total‑C be used to monitor therapy.
Although Mevacor may be useful to reduce elevated LDL‑C levels in patients with combined hypercholesterolemia and hypertriglyceridemia where hypercholesterolemia is the major abnormality (Type IIb hyperlipoproteinemia), it has not been studied in conditions where the major abnormality is elevation of chylomicrons, VLDL or IDL (i.e., hyperlipoproteinemia types I, III, IV, or V).3
The NCEP classification of cholesterol levels in pediatric patients with a familial history of hypercholesterolemia or premature cardiovascular disease is summarized below:
| Category | Total-C (mg/dL) | LDL-C (mg/dL) |
| Acceptable | <170 | <110 |
| Borderline | 170–199 | 110–129 |
| High | ≥200 | ≥130 |
