atorvastatin 40 mg tablet (generic lipitor)

Uses

Atorvastatin is used as an adjunct to nondrug therapies (i.e., lifestyle modifications) for prevention of cardiovascular events and for the management of dyslipidemias.

Prevention of Cardiovascular Events

The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline recommends statins as first-line therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) in adults. There is extensive evidence demonstrating that statins can substantially reduce ASCVD risk when used for secondary prevention or primary prevention (in high-risk patients). Because the relative reduction in ASCVD risk is correlated with the degree of low-density lipoprotein (LDL)-cholesterol lowering, the maximum tolerated statin intensity should be used to achieve optimum ASCVD benefits. According to the ACC/AHA guidelines, atorvastatin may be used for primary or secondary prevention in adults when moderate- or high-intensity statin therapy is indicated.(See Prevention of Cardiovascular Events under Dosage and Administration: Dosage.) Nonstatin therapies do not provide acceptable ASCVD risk reduction benefits compared to their potential for adverse effects in the routine prevention of ASCVD. For additional details on prevention of ASCVD, and also consult the most recent ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (available at http://www.cardiosource.org or http://my.americanheart.org).

Primary Prevention

The ACC/AHA cholesterol management guideline states that, before initiating statin therapy for primary prevention in patients without clinical ASCVD or diabetes mellitus, it is reasonable for clinicians and patients to discuss the potential for ASCVD risk reduction benefits, adverse effects, and drug interactions, as well as patient preferences for treatment.

Patients without Clinical Evidence of CHD

Atorvastatin is used as an adjunct to nondrug therapies (i.e., lifestyle modifications) in patients without clinical evidence of coronary heart disease (CHD) who have multiple risk factors (e.g., age, smoking, hypertension, low high-density lipoprotein [HDL]-cholesterol concentrations, family history of early CHD) to reduce the risk of myocardial infarction (MI), stroke, or angina, and to reduce the risk of undergoing revascularization procedures. Atorvastatin in fixed combination with amlodipine is used in patients for whom treatment with both atorvastatin and a calcium-channel blocking agent (i.e., amlodipine) is appropriate.

The ACC/AHA cholesterol management guideline recommends statins as first-line therapy for primary prevention in patients 21 years of age and older without clinical ASCVD who have primary, severe elevations in LDL-cholesterol concentration (190 mg/dL or greater) and in patients 40-75 years of age with LDL-cholesterol concentrations of 70-189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher.

Safety and efficacy of atorvastatin for primary prevention of cardiovascular disease have been established in several randomized, double-blind, placebo-controlled studies in patients without clinical evidence of CHD. In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) in 10,305 hypertensive, hypercholesterolemic (total cholesterol 251 mg/dL or less) patients with no history of MI who had multiple risk factors for CHD, therapy with atorvastatin (10 mg daily) for a median of 3.3 years reduced the risk of coronary events (i.e., fatal CHD or nonfatal MI) by 36% and the risk of undergoing revascularization procedures by 42%. Lipoprotein concentrations were lowered to levels similar to those observed with atorvastatin 10 mg daily in previous clinical studies. The risk of fatal and nonfatal stroke was reduced by 26%, although this was not statistically significant. Treatment with atorvastatin did not reduce the risk of death from cardiovascular or noncardiovascular causes.

In the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study in hypercholesterolemic patients (LDL-cholesterol concentrations of 100-190 mg/dL) who had a stroke or transient ischemic attack (TIA) within the past 1-6 months, therapy with high-dose atorvastatin (80 mg daily) for a median of 4.9 years reduced the risk of subsequent nonfatal or fatal stroke and of major cardiovascular events by approximately 16 and 20%, respectively, compared with placebo. However, atorvastatin therapy did not reduce overall mortality. In addition, hemorrhagic stroke and elevated aminotransferase (transaminase) concentrations (to at least 3 times the upper limit of normal) were reported in more patients receiving atorvastatin than in those receiving placebo.(See Use in Patients with Recent Stroke or Transient Ischemic Attack under Cautions: Precautions/Contraindications.) Some clinicians state that the results of this study should be interpreted with caution due to the heterogeneity of enrolled patients (i.e., with respect to stroke etiology and vascular risk). Furthermore, because patients with atrial fibrillation or other cardiac sources of embolism were excluded from the study, it is not known whether the observed benefits of atorvastatin apply to ischemic strokes of cardioembolic origin.

Patients with Diabetes Mellitus

Atorvastatin is used as an adjunct to nondrug therapies (i.e., lifestyle modifications) in patients without clinical evidence of CHD who have type 2 diabetes mellitus and multiple risk factors for CHD (e.g., retinopathy, albuminuria, smoking, hypertension) to reduce the risk of MI or stroke. Atorvastatin in fixed combination with amlodipine is used in patients for whom treatment with both atorvastatin and a calcium-channel blocking agent (i.e., amlodipine) is appropriate.

The ACC/AHA cholesterol management guideline recommends statins as first-line therapy for primary prevention in patients 40-75 years of age with type 1 or 2 diabetes mellitus. In patients with diabetes mellitus who are younger than 40 or older than 75 years of age, it is reasonable to evaluate the potential benefits, adverse effects, drug interactions, and patient preferences when deciding to initiate, continue, or intensify statin therapy.

Safety and efficacy of atorvastatin for prevention of cardiovascular disease in patients with type 2 diabetes mellitus have been established in a randomized, double-blind, placebo-controlled study. In the Collaborative Atorvastatin Diabetes Study (CARDS) in 2838 hypercholesterolemic patients (median total cholesterol concentration of 207 mg/dL, LDL-cholesterol concentration of 120 mg/dL, triglyceride concentration of 151 mg/dL) with type 2 diabetes mellitus (mean hemoglobin A_1c [HbA_1c] of 7.7%) and one or more other risk factors (e.g., smoking, hypertension, retinopathy, microalbuminuria, macroalbuminuria), therapy with atorvastatin (10 mg daily) for a median of 3.9 years reduced the risk of stroke by 48% and the risk of MI by 42% compared with placebo. Lipoprotein concentrations were lowered to levels similar to those observed with atorvastatin 10 mg daily in previous clinical studies. Treatment with atorvastatin did not reduce the risk of unstable angina, revascularization procedures, or acute CHD death.

The addition of fenofibrate to statin therapy has not been shown to provide an incremental ASCVD risk reduction benefit beyond that already established with statin monotherapy. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD Lipid) study in patients with type 2 diabetes mellitus, addition of fenofibrate (160 mg once daily) to simvastatin therapy (up to 40 mg once daily) did not further reduce the rate of fatal cardiovascular events, nonfatal MI, or nonfatal stroke compared with simvastatin alone.

Secondary Prevention

Patients with Clinical Evidence of CHD

Atorvastatin is used as an adjunct to nondrug therapies (i.e., lifestyle modifications) in patients with clinical evidence of CHD to reduce the risk of nonfatal MI, fatal and nonfatal stroke, angina, or hospitalization for congestive heart failure (CHF), and to reduce the risk of undergoing revascularization procedures. Atorvastatin in fixed combination with amlodipine is used in patients for whom treatment with both atorvastatin and a calcium-channel blocking agent (i.e., amlodipine) is appropriate.

The ACC/AHA cholesterol management guideline recommends statins as first-line therapy for secondary prevention in patients 21-75 years of age who have clinical ASCVD (i.e., acute coronary syndromes; history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) unless contraindicated.

Safety and efficacy of atorvastatin for secondary prevention of cardiovascular disease were established in several randomized studies in patients with clinically evident CHD. In one randomized, double-blind study (Treating to New Targets [TNT]) in 10,001 patients with clinically evident CHD (i.e., history of MI, history of or current angina with objective evidence of atherosclerotic CHD, history of coronary revascularization) and LDL-cholesterol concentrations less than 130 mg/dL, treatment with intensive antilipemic therapy (atorvastatin 80 mg daily) or moderate antilipemic therapy (atorvastatin 10 mg daily) for a median of 4.9 years reduced LDL-cholesterol concentrations to a mean of 77 or 101 mg/dL, respectively. Compared with the moderate regimen, treatment with the intensive regimen resulted in a 22% relative reduction in the risk of the primary composite end point (i.e., death from CHD, nonfatal non-procedure-related MI, resuscitated cardiac arrest, and fatal or nonfatal stroke). Of the events that comprised the primary composite end point, treatment with the intensive regimen substantially reduced the rate of nonfatal non-procedure-related MI and fatal and nonfatal stroke, but not death from CHD or resuscitated cardiac arrest. Of the predefined secondary end points, treatment with the intensive regimen reduced the rate of coronary revascularization, angina, and hospitalization for CHF, but not peripheral vascular disease. The intensive regimen did not reduce overall mortality and was associated with a slightly (but not statistically significant) increased risk of death from noncardiovascular causes. In addition, severe adverse effects (e.g., increases in concentrations of aminotransferase or creatine kinase [CK, creatine phosphokinase, CPK] to at least 3 or 10 times greater than the upper limit of normal, respectively) and discontinuance of therapy due to adverse effects were more common in patients receiving the intensive regimen compared with the moderate regimen. In a post hoc analysis in 5584 patients with CHD and the metabolic syndrome, treatment with the intensive regimen was associated with a lower incidence of major cardiovascular events than treatment with the moderate regimen (9.5 versus 13%); this represented a 29% relative reduction in the risk of major cardiovascular events in favor of the intensive regimen. However, consistent with the overall population, the intensive regimen did not reduce overall mortality compared with the moderate regimen.

In a randomized, comparative study (Incremental Decrease in Endpoints through Aggressive Lipid Lowering [IDEAL]) in 8888 patients with a history of CHD and an average LDL-cholesterol concentration of approximately 122 mg/dL, treatment with atorvastatin (80 mg daily) or simvastatin (20-40 mg daily) for a median of 4.8 years resulted in similar reduction in the risk of the primary composite end point (i.e., fatal CHD, nonfatal MI, and resuscitated cardiac arrest). In addition, no difference in overall mortality was observed between atorvastatin- or simvastatin-treated patients, and the rates of death from cardiovascular or noncardiovascular causes were similar in both treatment groups.

In a multicenter, randomized, open-label study comparing the incidence of ischemic events in CHD patients undergoing angioplasty or receiving aggressive lipid-lowering therapy with atorvastatin 80 mg daily (Atorvastatin Versus Revascularization Treatments [AVERT] trial), atorvastatin was as effective as angioplasty in reducing the incidence of ischemic events (defined as death from cardiac causes, resuscitation after cardiac arrest, nonfatal MI, cerebrovascular accident, coronary artery bypass grafting, angioplasty, or worsening angina with objective evidence resulting in hospitalization) and delaying the onset of the first ischemic event. However, atorvastatin-treated patients had smaller increases in quality of life scores and were more likely to report worsening of angina (12 versus 7%) compared with patients in the angioplasty group.

High-intensity Statin Therapy

Early and intensive antilipemic therapy with a high dosage of atorvastatin has been shown to be more effective than a moderate dosage of a statin in reducing the risk of cardiovascular events in patients with acute coronary syndrome (ACS).

In a randomized, double-blind, placebo-controlled study (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering [MIRACL]) in patients with unstable angina or non-ST-segment elevation (e.g., non-Q-wave) acute MI, therapy with atorvastatin (80 mg daily), initiated within 24-96 hours after admittance to the hospital, was associated with a lower incidence of recurrent ischemic events (particularly symptomatic ischemia requiring rehospitalization) in the subsequent 16 weeks; however, the validity of these results has been questioned due to the large number of atorvastatin-treated patients lost during follow-up.

In a randomized, double-blind, study (Pravastatin or Atorvastatin Evaluation and Infection Therapy [PROVE-IT]) in over 4000 patients hospitalized for ACS within the preceding 10 days, treatment with intensive antilipemic therapy (atorvastatin 80 mg daily) or moderate antilipemic therapy (pravastatin 40 mg daily) for 2 years reduced LDL-cholesterol concentrations to a median of 62 or 95 mg/dL, respectively. Compared with the moderate regimen, treatment with the intensive regimen resulted in a 16% reduction in the composite risk of primary endpoints, including a 14% reduction in the need for revascularization procedures and a 29% reduction in the risk of recurrent unstable angina. Atorvastatin therapy also was associated with reductions in the rates of death from any cause (28%) and of death or MI (18%) compared with pravastatin therapy, but these differences were not statistically significant. Results of this study suggest that, among patients who have recently had an acute coronary syndrome, an intensive antilipemic regimen provides greater protection against death or major cardiovascular events than does a standard regimen.

Reducing Progression of Coronary Atherosclerosis

Intensive antilipemic therapy with atorvastatin has been shown to slow the progression of coronary atherosclerosis in patients with CHD. In a randomized, double-blind, active-control study (Reversal of Atherosclerosis with Aggressive Lipid Lowering [REVERSAL]) in 654 patients with CHD, treatment with intensive antilipemic therapy (atorvastatin 80 mg daily) or moderate antilipemic therapy (pravastatin 40 mg daily) for 18 months reduced LDL-cholesterol concentrations to a mean of 79 or 110 mg/dL, respectively; concentrations of C-reactive protein were reduced by 36.4% in atorvastatin-treated patients and by 5.2% in pravastatin-treated patients. Treatment with the intensive regimen was associated with a substantially lower progression rate (measured by percent change in atheroma volume) compared with treatment with the moderate regimen. Compared with baseline values, patients treated with atorvastatin had no change in atheroma burden, whereas patients treated with pravastatin showed progression of coronary atherosclerosis. It has been suggested that the differences in atherosclerosis progression between atorvastatin and pravastatin may be related to the greater reduction in atherogenic lipoproteins and C-reactive protein concentrations in patients treated with atorvastatin.

Intensity of Statin Therapy

The ACC/AHA cholesterol management guideline states that the appropriate intensity of a statin should be used to reduce the risk of ASCVD in patients most likely to benefit. Based on the average LDL-cholesterol response observed with specific statins and dosages used in the randomized controlled studies evaluated by the guideline expert panel, ACC/AHA considers atorvastatin 10-20 mg daily to be a moderate-intensity statin (producing approximate LDL-cholesterol reductions of 30% to less than 50%) and atorvastatin 40-80 mg daily to be a high-intensity statin (producing average LDL-cholesterol reductions of at least 50%). Individual patient response may vary in clinical practice.

Combination Antilipemic Therapy

The ACC/AHA cholesterol management guideline states that nonstatin drugs may be useful adjuncts to statin therapy in certain high-risk patients (e.g., patients with ASCVD, LDL-cholesterol concentrations of at least 190 mg/dL, or diabetes mellitus) who have a less-than-anticipated response to statins, are unable to tolerate a less-than-recommended intensity of a statin, or are completely intolerant to statin therapy, particularly if there is evidence from randomized controlled studies suggesting that the addition of the nonstatin drug further reduces ASCVD events. If combination therapy is necessary, selection of the nonstatin drug should be based on the risk and benefit profile (i.e., reduction in ASCVD risk outweighs the drug's potential for adverse effects and drug interactions) and patient preferences.

Patients with Chronic Kidney Disease

The potential benefits of atorvastatin in patients with chronic kidney disease, a population at high risk of cardiovascular disease, were evaluated in the Deutsche Diabetes Dialyse Studie (4D), a randomized, double-blind, placebo-controlled study in 1255 patients with type 2 diabetes mellitus on maintenance hemodialysis. After a median follow-up of 4 years, therapy with atorvastatin 20 mg daily had no substantial effect on the primary composite end point of cardiovascular death, nonfatal MI, and stroke compared with placebo. Although atorvastatin reduced the rate of all cardiac events (a secondary end point in the study) relative to placebo, the difference was only nominally significant.

Dyslipidemias

Atorvastatin is used as an adjunct to nondrug therapies (e.g., dietary management) for the management of primary hypercholesterolemia or mixed dyslipidemia (Fredrickson type IIa or IIb), hypertriglyceridemia (Fredrickson type IV), primary dysbetalipoproteinemia (Fredrickson type III), and/or homozygous familial hypercholesterolemia. Atorvastatin has not been studied in conditions where the principal lipoprotein abnormality is elevated chylomicrons (Fredrickson types I and V). Atorvastatin in fixed combination with amlodipine is used in patients for whom treatment with both atorvastatin and a calcium-channel blocking agent (i.e., amlodipine) is appropriate.

Primary Hypercholesterolemia or Mixed Dyslipidemia

Adults

Atorvastatin, alone or in combination with ezetimibe, is used as an adjunct to nondrug therapies (e.g., dietary management) in adults to decrease elevated serum total and LDL-cholesterol, apolipoprotein B (apo B), and triglyceride concentrations, and to increase HDL-cholesterol concentrations in the management of primary hypercholesterolemia (heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIa or IIb). Statins such as atorvastatin also are used in combination with fenofibrate to decrease triglyceride concentrations and increase HDL-cholesterol concentrations in patients with mixed dyslipidemia and CHD (or CHD risk equivalents) who are receiving optimal statin therapy; however, no additional benefit on cardiovascular morbidity and mortality has been demonstrated with such combination therapy beyond that already established with statin monotherapy.(See Patients with Diabetes Mellitus under Prevention of Cardiovascular Events: Primary Prevention, under Uses.)

Reductions in total and LDL-cholesterol concentrations produced by usual dosages of atorvastatin substantially exceed those of placebo. Mean reductions of 29-45% in total cholesterol, 39-60% in LDL-cholesterol, 32-50% in apo B, and 19-37% in triglyceride concentrations, and increases of 5-9% in HDL-cholesterol concentrations have been reported in 2 controlled studies in 107 patients with primary hypercholesterolemia who received atorvastatin 10-80 mg daily for 6 weeks. Increases in HDL-cholesterol concentrations also have been observed in other studies in patients with primary hypercholesterolemia or mixed dyslipidemia; pooled data from 24 controlled studies indicate median increases of 5-9% in HDL-cholesterol concentrations in patients receiving atorvastatin 10-80 mg daily. Analysis of pooled data demonstrated consistent and substantial decreases in total cholesterol, LDL-cholesterol, triglyceride, total-cholesterol/HDL-cholesterol ratio, and LDL-cholesterol/HDL-cholesterol ratio in patients receiving atorvastatin. In patients with dyslipidemia and hypertension who received atorvastatin (10-80 mg daily) in combination with amlodipine (5-10 mg daily), LDL-cholesterol concentrations were reduced by 36-48% following 8 weeks of therapy.

Data from comparative studies indicate that therapy with atorvastatin may produce greater reductions in total and LDL-cholesterol concentrations than certain other statins. In 3 multicenter, double-blind, comparative studies, patients with hypercholesterolemia who received atorvastatin 10 mg daily for 16 weeks experienced greater reductions in total and LDL-cholesterol concentrations (25-29 and 35-37%, respectively) than those receiving lovastatin 20 mg daily (19 and 27%, respectively), pravastatin 20 mg daily (17 and 23%, respectively), or simvastatin 10 mg daily (24 and 30%, respectively). In other multicenter, randomized, open-label, comparative studies, patients with hypercholesterolemia who received atorvastatin 10-40 mg daily experienced greater reductions in total and LDL-cholesterol concentrations (25-40 and 35-51%, respectively) than those receiving fluvastatin 20-40 mg daily (13-19 and 17-23%, respectively), lovastatin 20-40 mg daily (21-23 and 29-31%, respectively), pravastatin 10-40 mg daily (13-24 and 19-34%, respectively), or simvastatin 10-40 mg daily (21-31 and 28-41%, respectively). The impact of differences in antilipemic effects between various statins on clinical outcomes is not known.

Compared with certain other statins, the effects of atorvastatin on HDL-cholesterol concentrations may be less pronounced, particularly with higher doses of atorvastatin. In several studies designed to evaluate the effects of atorvastatin (20-80 mg daily) and simvastatin (40-80 mg) on HDL-cholesterol and apolipoprotein (apo) A-I concentrations, increases in HDL-cholesterol and apo A-I concentrations were greater with simvastatin therapy (7-9 and 3-6%, respectively) than with atorvastatin (0-7 and 0-5%, respectively). The mechanisms of these effects have not been fully elucidated but may be related to differences in the 2 drugs' plasma elimination half-lives (approximately 20 and 2 hours for atorvastatin and simvastatin, respectively) and/or differential effects of the drugs on lipolytic enzymes (e.g., lipoprotein lipase, hepatic lipase).

Limited data from comparative studies suggest that reductions in total and LDL-cholesterol concentrations produced by atorvastatin may exceed those produced by fibric acid derivatives. In an open-label study in patients with mixed dyslipidemia, treatment with atorvastatin (10 mg daily) was associated with greater reductions in serum total and LDL-cholesterol concentrations compared with fenofibrate therapy (200 mg daily); however, fenofibrate-treated patients had greater reductions in triglyceride concentrations and larger increases of HDL-cholesterol and apo A-I concentrations than those who received atorvastatin.

The combination of atorvastatin and other antilipemic agents (e.g., bile acid sequestrants, ezetimibe) generally results in additive antilipemic effects; however, the risk of myopathy and rhabdomyolysis may be increased.(See Combination Antilipemic Therapy under Uses: Prevention of Cardiovascular Events.) The addition of a bile acid sequestrant (e.g., colestipol 20 g daily) to atorvastatin therapy (10 mg daily) further reduced LDL-cholesterol by 10%, resulting in an overall LDL-cholesterol reduction of 45% in patients receiving the combination; however, frequent adverse effects (e.g., GI effects such as constipation) reported with this combination regimen may discourage adherence to therapy. The addition of ezetimibe (10 mg daily) to atorvastatin therapy (10-80 mg daily) further reduced LDL-cholesterol by 7-16%, resulting in an overall LDL-cholesterol reduction of 53-61%.

Pediatric Patients

Atorvastatin is used as an adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum total cholesterol, LDL-cholesterol, and apo B concentrations in the management of heterozygous familial hypercholesterolemia in boys and postmenarchal girls 10-17 years of age who, despite an adequate trial of dietary management, have a serum LDL-cholesterol concentration of 190 mg/dL or greater or a serum LDL-cholesterol concentration of 160 mg/dL or greater and either a family history of premature cardiovascular disease or 2 or more other cardiovascular risk factors. The long-term effect of atorvastatin therapy in childhood on reducing cardiovascular morbidity and mortality in adulthood has not been established. For additional details on management of dyslipidemias in pediatric patients, and also consult the most recent Integrated Guideline for Cardiovascular Health and Risk Reduction in Children and Adolescents (available at http://www.nhlbi.nih.gov).

In a double-blind, placebo-controlled study (followed by an open-label phase), 187 boys and postmenarchal girls 10-17 years of age with heterozygous familial hypercholesterolemia or severe hypercholesterolemia (mean baseline LDL-cholesterol concentration of 219-230 mg/dL) were randomized to receive either atorvastatin (10 mg daily for the first 4 weeks, increased to 20 mg daily if LDL-cholesterol concentration exceeded 130 mg/dL) or placebo for 26 weeks; after 26 weeks of the double-blind phase, all patients entered an open-label phase and received atorvastatin for an additional 26 weeks. During the 26-week double-blind phase, treatment with atorvastatin 10-20 mg daily resulted in mean reductions of 31% in total cholesterol, 40% in LDL-cholesterol, 34% in apo B, and 12% in triglyceride concentrations, while concentrations of these lipoprotein fractions in placebo recipients changed minimally. HDL-cholesterol concentrations increased by 2.8% in atorvastatin-treated patients and decreased by 1.9% in placebo recipients. The mean LDL-cholesterol concentration achieved with atorvastatin therapy was 130.7 mg/dL compared with 228.5 mg/dL achieved with placebo during the 26-week double-blind phase.

Hypertriglyceridemia

Atorvastatin is used as an adjunct to nondrug therapies (e.g., dietary management) in the treatment of elevated serum triglyceride concentrations (Fredrickson type IV). AHA states that although statins have consistently shown benefit in subgroups with or without high triglyceride concentrations, fibric acid derivatives have more commonly been shown to provide greater benefit in subgroups with increased triglyceride concentrations.

While statins are effective in reducing LDL-cholesterol concentrations, most statins generally have a limited effect on serum triglyceride concentrations. However, limited data suggest that triglyceride reductions produced by usual dosages of atorvastatin substantially exceed those of placebo and appear to be similar to those reported with usual dosages of fibrates or niacin. In several clinical studies in 64 patients with isolated hypertriglyceridemia, treatment with atorvastatin (10-80 mg daily) resulted in median reductions of 39-52% in triglyceride, 28-44% in total cholesterol, 27-41% in LDL-cholesterol, 45-62% in very low-density lipoprotein (VLDL)-cholesterol, and 33-52% in non-HDL-cholesterol concentrations, and a median increase of 8-14% in HDL-cholesterol concentrations; however, no patient achieved normal triglyceride concentrations as a result of treatment.

Atorvastatin 10 mg daily reportedly has produced greater reductions in LDL-cholesterol than niacin 3 g daily or fenofibrate 300 mg daily in patients with combined hyperlipidemia or isolated hypertriglyceridemia. However, reductions in triglyceride concentrations and increases in HDL-cholesterol concentrations were less than those reported with usual dosages of niacin or fenofibrate.

Primary Dysbetalipoproteinemia

Atorvastatin is used as an adjunct to nondrug therapies (e.g., dietary management) for the treatment of primary dysbetalipoproteinemia (Fredrickson type III) in patients who do not respond adequately to diet.

In an open-label, crossover study in 16 patients with primary dysbetalipoproteinemia (genotypes 14 apo E2/E2 and 2 apo E3/E2), treatment with atorvastatin (10 or 80 mg daily) for at least 8 weeks resulted in substantial reductions in total cholesterol (37 or 58%, respectively), triglyceride (39 or 53%, respectively), combined intermediate-density lipoprotein (IDL)- and VLDL-cholesterol (32 or 63%, respectively), and non-HDL-cholesterol concentrations (43 or 64%, respectively).

Homozygous Familial Hypercholesterolemia

Atorvastatin is used alone or in combination with ezetimibe to decrease elevated serum total and LDL-cholesterol concentrations in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies (e.g., plasma LDL-apheresis) or when such therapies are not available. Patients with homozygous familial hypercholesterolemia usually respond poorly to combined dietary management and drug therapy, including regimens containing a statin, in part because these patients have poorly functioning, few, or no LDL receptors. In an uncontrolled study in 29 patients 6-37 years of age with homozygous familial hypercholesterolemia, LDL-cholesterol concentrations were reduced by 7-53% (mean reduction of 20%) in 25 of 29 patients (86%) and increased by 7-24% in 4 of 29 patients (14%) who received atorvastatin dosages of 20-80 mg daily; 5 of the 29 patients had absent LDL-receptor function (of these, 2 patients also had a portacaval shunt and had no substantial reduction in LDL-cholesterol concentrations, and the remaining 3 receptor-negative patients had a mean LDL-cholesterol reduction of 22%). Similar reductions (17-28%) were observed in another open-label study in which patients received atorvastatin dosages of 40-80 mg daily for at least 4 weeks. In a limited number of patients undergoing plasma LDL-apheresis to lower cholesterol concentrations, addition of atorvastatin (80 mg daily) for 8 weeks reduced plasma total and LDL-cholesterol concentrations by an additional 29 and 31%, respectively. Limited evidence indicates that treatment with atorvastatin also may slow the progression of atherosclerosis in these patients.

In a randomized, double-blind study of 12 weeks' duration in a limited number of patients with a clinical and/or genotypic diagnosis of homozygous familial hypercholesterolemia, the addition of ezetimibe (10 mg daily) to atorvastatin or simvastatin therapy (40 or 80 mg daily) was more effective in reducing LDL-cholesterol concentrations (21% additional reduction based on pooled data from 40-mg and 80-mg statin groups) than increasing the dosage of atorvastatin or simvastatin monotherapy from 40 to 80 mg daily (7% additional reduction based on pooled data from 40-mg and 80-mg statin groups). In patients receiving ezetimibe (10 mg daily) in combination with higher dosages (80 mg daily) of atorvastatin or simvastatin, LDL-cholesterol concentrations were reduced by an additional 27% compared with LDL-cholesterol reductions achieved with the 40-mg daily statin dosage.

Other Uses

Atorvastatin has reduced total and LDL-cholesterol concentrations in a few patients with renal transplantation. In addition, the drug has reduced total and LDL-cholesterol concentrations in hypercholesterolemic patients on peritoneal dialysis. Atorvastatin, alone or in combination with gemfibrozil, also has been shown to reduce cholesterol and triglyceride concentrations in patients with hypercholesterolemia associated with the use of protease inhibitors.

For additional information on the role of atorvastatin or other statins in the treatment of lipoprotein disorders, prevention of cardiovascular events, or other uses, see General Principles of Antilipemic Therapy and see Uses in the HMG-CoA Reductase Inhibitors General Statement 24:06.08. For additional information on the use of amlodipine, see Uses in Amlodipine Besylate 24:28.08.