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, simvastatin may be used for primary or secondary prevention in adults when moderate-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).
Simvastatin is used as an adjunct to nondrug therapies (e.g., lifestyle modification) in patients with coronary heart disease (CHD) or CHD risk equivalents (i.e., risk factors that confer a risk for major coronary events equal to that of established CHD, such as diabetes mellitus, peripheral arterial disease, history of stroke or other cerebrovascular disease) to reduce the risk of total mortality by reducing CHD deaths, to reduce the risk of nonfatal myocardial infarction (MI) and stroke, and to reduce the need for coronary and noncoronary revascularization procedures.
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 [ACS]; history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack [TIA], or peripheral arterial disease presumed to be of atherosclerotic origin) unless contraindicated.
Several clinical trials designed to evaluate the benefits of simvastatin in patients with established CHD have reported improvements in the risk of cardiovascular events, as evidenced by reductions in the risks of total mortality and nonfatal coronary events. In the Scandinavian Simvastatin Survival Study (4S), therapy with simvastatin in 4444 patients with hypercholesterolemia and angina pectoris or prior MI was associated with reductions in total mortality (30%), CHD mortality (42%), and hospital-verified nonfatal MI (37%) compared with placebo over a median of 5.4 years of follow-up; the risk of undergoing myocardial revascularization procedures also was reduced by 37%. In addition, simvastatin therapy reduced the risk of fatal and nonfatal cerebrovascular events (combined incidence of stroke and TIA) by 28%. The reduction in the combined coronary events (nonfatal MI and revascularization procedures) reported in the 4S trial also was observed in women, geriatric patients (65 years of age and older), and in patients with diabetes mellitus. Unlike some prior studies of cholesterol-lowering therapy, an increased risk of death from noncardiovascular causes was not observed in patients receiving simvastatin therapy in this study.
In the Heart Protection Study (HPS), therapy with simvastatin (40 mg daily) in over 20,000 patients with CHD, history or stroke or other cerebrovascular disease, other occlusive arterial disease (e.g., peripheral arterial disease), hypertension or diabetes mellitus reduced the risk of total mortality (13%), CHD mortality (18%), nonfatal MI (38%), ischemic stroke (25%), coronary revascularization procedures (30%), and peripheral and other noncoronary revascularization procedures (16%) compared with placebo over approximately 5 years of follow-up, irrespective of baseline lipoprotein concentrations.
In another randomized, double-blind study (A to Z trial) in about 4500 patients who had manifestations of ACS within the preceding 5 days, treatment with intensive antilipemic therapy (simvastatin 40 mg daily for 1 month, then simvastatin 80 mg daily thereafter) for 6-24 months resulted in a 25% reduction in the risk of cardiovascular mortality compared with moderate antilipemic therapy (placebo for 4 months, then simvastatin 20 mg daily thereafter); there was a reduction (11%) in the rate of the primary endpoint (a composite of cardiovascular death, nonfatal MI, readmission for ACS, and stroke) for the entire study period but this difference failed to reach statistical significance. However, while no difference was evident between the intensive and moderate regimens during the first 4 months of therapy, from 4 months through the end of the study, the primary endpoint was substantially reduced (by 25%) in patients receiving the intensive regimen. Intensive or moderate antilipemic therapy reduced LDL-cholesterol concentrations to a median of 63 or 77 mg/dL, respectively, at 8 months. While a favorable trend toward reduction of major cardiovascular events was observed in this study, it is possible that more intensive therapy is required immediately after the onset of ACS during the period of greatest clinical instability to achieve a more rapid clinical benefit.
Simvastatin has been shown to slow the progression and/or induce regression of atherosclerosis in coronary arteries by reducing intimal-medial wall thickness. In the Multicenter Anti-Atheroma Study (MAAS) in hypercholesterolemic men and women with clinical evidence of CHD, progression of atherosclerosis at 2-4 years (measured as the mean per-patient changes from baseline in mean and minimal coronary artery lumen diameters, diameter stenosis, and formation of new lesions) was reduced in patients who received simvastatin (20 mg daily) compared with those receiving placebo.
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 simvastatin 10 mg daily to be a low-intensity statin (producing approximate LDL-cholesterol reductions of less than 30%) and simvastatin 20-40 mg daily to be a moderate-intensity statin (producing approximate LDL-cholesterol reductions of 30% to less than 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.
Although early findings from the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) study demonstrated that combination therapy with simvastatin and ezetimibe was not superior to simvastatin monotherapy in reducing carotid intimal-medial wall thickness (cIMT), a more recent study (the Improved Reduction of Outcomes: Vytorin Efficacy International [IMPROVE-IT]) in 18,144 post-ACS patients with baseline LDL-cholesterol concentrations of 50-125 mg/dL (or 50-100 mg/dL if they were receiving lipid-lowering therapy) showed that the addition of ezetimibe (10 mg daily) to simvastatin (40 mg daily) therapy not only produced a 24% further reduction in LDL-cholesterol concentrations, but also improved cardiovascular outcomes (a composite of cardiovascular death, nonfatal MI, unstable angina requiring hospitalization, coronary revascularization, or nonfatal stroke) compared with simvastatin (40 mg daily) monotherapy. Treatment with the simvastatin and ezetimibe combination resulted in an absolute risk reduction of 2% over 7 years for the primary composite end point.
The addition of niacin to statin-based therapy has not been shown to provide an incremental benefit in reducing cardiovascular morbidity and mortality beyond that already demonstrated with statin-based therapy. In the Impact on Global Health Outcomes (AIM-HIGH) study, the combination of extended-release niacin (1.5-2 g daily) and statin-based therapy (simvastatin 40-80 mg once daily, with or without ezetimibe 10 mg daily) was compared with statin-based therapy alone in patients with established cardiovascular disease (i.e., documented stable CHD, cerebrovascular or carotid disease, peripheral arterial disease). Despite a favorable effect on serum lipid concentrations (median high-density lipoprotein [HDL]-cholesterol concentration increased from 35 to 42 mg/dL, triglyceride concentration decreased from 164 to 122 mg/dL, and LDL-cholesterol concentration decreased from 74 to 62 mg/dL), the addition of niacin to simvastatin-based therapy did not further reduce the incidence of the primary end point (i.e., composite of death from CHD, nonfatal MI, ischemic stroke, hospitalization for more than 23 hours for ACS, or symptom-driven coronary or cerebral revascularization) compared with simvastatin-based therapy alone over a follow-up period of 36 months. The addition of extended-release niacin to existing simvastatin-based therapy, however, did increase the risk of adverse effects (e.g., pruritus, flushing, adverse GI effects, increased blood glucose concentrations). The investigators of this study stated that whether such combination therapy provides incremental benefit in higher-risk patients or in those receiving suboptimal statin therapy remains to be established.
Data from another large randomized, double-blind, multicenter study involving 25,673 adults with cardiovascular disease confirmed findings of the AIM-HIGH study. In the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), the combination of extended-release niacin/laropiprant (2 g/40 mg daily) (no longer commercially available) and statin-based therapy (simvastatin 40 mg once daily, with or without ezetimibe 10 mg daily) was compared with statin-based therapy alone in patients with established cardiovascular disease (i.e., history of MI, cerebrovascular disease, peripheral arterial disease, diabetes mellitus with evidence of symptomatic coronary disease). Despite a favorable effect on serum lipid concentrations (additional 6-mg/dL increase in HDL-cholesterol concentration, 33-mg/dL reduction in triglyceride concentration, and 10-mg/dL reduction in LDL-cholesterol concentration), the addition of niacin/laropiprant to simvastatin-based therapy did not further reduce the incidence of major cardiovascular events (i.e., nonfatal MI, death from coronary causes, stroke of any type, coronary or noncoronary revascularization) compared with simvastatin-based therapy alone over a median follow-up of 3.9 years. The addition of niacin/laropiprant to existing simvastatin-based therapy, however, did increase the risk of severe adverse effects, including disturbances in glycemic control requiring hospitalization, development of diabetes mellitus, adverse GI effects, myopathy, gout, rash, skin ulceration, and, unexpectedly, infection and bleeding.
Patients with Chronic Kidney Disease
In the Study of Heart and Renal Protection (SHARP), the fixed-combination preparation containing ezetimibe and simvastatin was shown to reduce the risk of major vascular and atherosclerotic events in patients with chronic kidney disease, a population known to be at increased risk of cardiovascular disease. More than 9000 patients with moderate to severe chronic kidney disease (33% receiving dialysis) and no known history of MI or coronary revascularization were initially randomized in a 4:4:1 ratio to receive the fixed-combination preparation containing ezetimibe and simvastatin (10 and 20 mg daily, respectively), placebo, or simvastatin alone (20 mg daily) for 1 year to assess the safety of adding ezetimibe to simvastatin; patients in the simvastatin monotherapy group were then re-randomized to the fixed-combination preparation or placebo. After a median duration of follow-up of 4.9 years, the risk of a major vascular event (nonfatal MI or cardiac death, stroke, or revascularization excluding dialysis access procedures) was reduced by 16% (based on the primary intent-to-treat analysis in patients initially randomized to the fixed-combination preparation or placebo groups) and the risk of a major atherosclerotic event (nonfatal MI or cardiac death, nonhemorrhagic stroke, or arterial revascularization excluding dialysis access procedures) was reduced by 17% (based on all patients randomized at any time to the fixed-combination preparation or placebo groups) with the fixed-combination preparation compared with placebo. The treatment effect was largely driven by a substantial reduction in ischemic strokes and arterial revascularization procedures. The subgroup of patients receiving dialysis at baseline experienced a smaller risk reduction benefit compared with those not receiving dialysis. In addition, therapy with the fixed-combination preparation did not appear to slow the progression to end-stage renal disease.
Simvastatin is used as an adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), triglyceride, and very low-density lipoprotein (VLDL)-cholesterol concentrations, and to increase HDL-cholesterol concentrations in the management of primary hyperlipidemia of primary or mixed dyslipidemia, homozygous familial hypercholesterolemia, primary dysbetalipoproteinemia, and/or hypertriglyceridemia. The efficacy of simvastatin remains to be established in patients with elevated chylomicrons as their primary lipid abnormality (Fredrickson types I and V).
Nondrug therapies and measures specific for the type of dyslipidemia (therapeutic lifestyle changes) are the initial treatments of choice, including dietary management (e.g., restriction of total and saturated fat and cholesterol intake, addition of plant stanols/sterols and viscous fiber to diet), weight control, an appropriate program of physical activity, and management of potentially contributory disease. Drug therapy is not a substitute for but an adjunct to these nondrug therapies and measures, which should be continued when drug therapy is initiated.
Primary Hyperlipidemia or Mixed Dyslipidemia
Simvastatin is used alone or in combination with ezetimibe as an adjunct to nondrug therapies (e.g., dietary management) in adults to decrease elevated serum total and LDL-cholesterol, apo B, and triglyceride concentrations, and to increase HDL-cholesterol concentrations in the treatment of primary hyperlipidemia (heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIa or IIb). Simvastatin also is used to decrease elevated serum total cholesterol, LDL-cholesterol, and apo B concentrations in the treatment of heterozygous familial hypercholesterolemia in boys and girls (at least one year postmenarchal) 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 simvastatin therapy in childhood on reducing cardiovascular morbidity and mortality in adulthood has not been established. Statins such as simvastatin 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 established with such combination therapy beyond that already established with statin monotherapy.
Reductions in total and LDL-cholesterol produced by usual dosages of simvastatin substantially exceed those of placebo and appear to be similar to or greater than those produced by monotherapy with certain other antilipemic agents. Mean reductions in total cholesterol concentrations of 19-36%, LDL-cholesterol concentrations of 26-47%, apo B concentrations of 31-38%, and triglyceride concentrations of 12-33% have been reported in controlled studies in patients with primary hypercholesterolemia who received 5-80 mg of simvastatin daily for at least 6 weeks. Modest and variable increases in HDL-cholesterol concentrations (5-16%) also were observed in these patients.
Reductions in total and LDL-cholesterol concentrations produced by usual dosages of simvastatin appear to be similar to or greater than those produced by monotherapy with most other statins (e.g., fluvastatin, lovastatin, pravastatin). In several randomized, comparative studies with various statins, patients with hypercholesterolemia who received simvastatin 5-40 mg daily had greater reductions in plasma total and LDL-cholesterol concentrations (16-30 and 21-41%, respectively) than those who received fluvastatin 20-40 mg daily (12-19 and 16-23%, respectively), lovastatin 20-40 mg daily (21-23 and 29-31%, respectively), or pravastatin 10-40 mg daily (13-24 and 19-34%, respectively). However, patients treated with atorvastatin 10-40 mg daily had greater reductions in total and LDL-cholesterol concentrations (28-40 and 38-51%, respectively) than simvastatin-treated patients. Furthermore, atorvastatin (40 mg daily) appears to be more effective than simvastatin (40 mg daily) in the management of patients with severe hypercholesterolemia who require regular plasma LDL-apheresis. Limited data indicate that reductions in LDL-cholesterol concentrations may be similar among patients receiving high-dose simvastatin and atorvastatin (80 mg daily).
Increases in HDL-cholesterol concentrations appear to be greater among simvastatin- than atorvastatin-treated patients. In several studies designed to evaluate the effects of simvastatin (40-80 mg) and atorvastatin (20-80 mg daily) on HDL-cholesterol and apolipoprotein A-I (apo A-I) concentrations, increases in HDL-cholesterol and apo A-I concentrations were more pronounced in simvastatin-treated (7-9 and 3-6%, respectively) patients than in atorvastatin-treated (0-7 and 0-5%, respectively) patients. The mechanisms of these effects have not been fully elucidated but may be related to differences in plasma elimination half-lives (approximately 20 hours for atorvastatin and 2 hours for simvastatin) and differential effects 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 simvastatin may be greater than those of some other antilipemic agents (i.e., bile acid sequestrants, fibric acid derivatives). In several controlled studies comparing 12 weeks of simvastatin therapy (20-40 mg daily) with that of cholestyramine (4-16 g in divided doses) in patients with familial and nonfamilial hypercholesterolemia, simvastatin was more effective than cholestyramine in reducing total and LDL-cholesterol concentrations (26-36 and 32-40% versus 23 and 15-21%, respectively). Simvastatin also was more effective than cholestyramine in improving triglyceride (21% reduction versus 11% increase) and HDL-cholesterol concentrations (16% versus 9% increase). Simvastatin appears to be more effective than fibric acid derivatives (e.g., gemfibrozil) in reducing total and LDL-cholesterol concentrations but less effective than these agents in reducing triglycerides and increasing HDL-cholesterol concentrations. In several randomized, comparative studies in patients with primary hypercholesterolemia, therapy with simvastatin (5-20 mg) produced greater reductions in total and LDL-cholesterol (14-27 and 22-34%, respectively) than treatment with gemfibrozil (600 mg twice daily) (5-14 and 17%, respectively); however, reductions in triglycerides and increases in HDL-cholesterol concentrations were less pronounced among patients treated with simvastatin (7-16% reduction and 6-13% increase) than in those receiving gemfibrozil (30-44% reduction and 16-26% increase). Similar results have been reported with other fibric acid derivatives (e.g., fenofibrate).
The combination of simvastatin and other antilipemic agents (e.g., bile acid sequestrants, fibric acid derivatives, ezetimibe) may produce additive antilipemic effects; however, the risk of myopathy and rhabdomyolysis may be increased with some combinations.
(See Combination Antilipemic Therapy under Uses: Prevention of Cardiovascular Events.)The addition of a bile acid sequestrant to simvastatin therapy further reduced LDL-cholesterol by 11%, resulting in an overall LDL-cholesterol reduction of 54% in patients receiving simvastatin 20-40 mg daily and cholestyramine 8-16 g daily. Low-dose simvastatin (10 mg daily) in combination with fenofibrate (300 mg daily) in patients with combined hyperlipidemia further reduced triglyceride concentrations by 32% and increased HDL-cholesterol concentrations by an additional 7%. In a multicenter, double-blind study, the addition of ezetimibe (10 mg daily) to simvastatin therapy (10-80 mg daily) further reduced LDL-cholesterol by 10-19%, resulting in overall LDL-cholesterol reductions of 46-58% with combined therapy. Similar additive antilipemic effects were observed following therapy with the fixed-combination preparation containing simvastatin and ezetimibe; LDL-cholesterol was reduced by 45-60% following therapy with the fixed-combination preparation and by 33-49% following monotherapy with simvastatin (10-80 mg daily). In another multicenter, double-blind study, the fixed-combination preparation containing 10 mg of ezetimibe and 20 mg of simvastatin was substantially more effective than doubling the dose of simvastatin (e.g., from 20 to 40 mg).
The increased risk of adverse muscular effects should be considered when simvastatin is used in combination with certain antilipemic agents (e.g., fibric acid derivatives or niacin at lipid-modifying dosages [at least 1 g daily]).
Homozygous Familial Hypercholesterolemia
Simvastatin 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 several open-label clinical trials in a limited number of patients with homozygous familial hypercholesterolemia receiving simvastatin 40-80 mg daily, LDL-cholesterol concentrations were reduced by 8-46% in most patients; however, at least one patient with homozygous familial hypercholesterolemia experienced increases (15%) in LDL-cholesterol concentrations with simvastatin therapy.
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 simvastatin or atorvastatin 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 simvastatin or atorvastatin 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 simvastatin or atorvastatin, LDL-cholesterol concentrations were reduced by an additional 27% compared with LDL-cholesterol reductions achieved with the 40-mg daily statin dosage.
Simvastatin is used as an adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum triglyceride and VLDL-cholesterol concentrations in the treatment of primary dysbetalipoproteinemia (Fredrickson type III).
Treatment with simvastatin has resulted in substantial reductions in combined intermediate-density lipoprotein (IDL)- and VLDL-cholesterol, total cholesterol, triglyceride, and non-HDL-cholesterol concentrations. In several studies in a limited number of patients with primary dysbetalipoproteinemia who received simvastatin 20-80 mg daily for at least 6 weeks, combined IDL- and VLDL-cholesterol, total cholesterol, triglyceride, and non-HDL-cholesterol concentrations decreased by 50-60, 39-54, 32-55, and 32-59%, respectively. Simvastatin 20 mg daily reportedly has produced greater reductions in LDL-cholesterol than gemfibrozil 1200 mg daily in patients with primary dysbetalipoproteinemia. However, reductions in triglyceride concentrations and increases in HDL-cholesterol concentrations were less pronounced than those reported with usual dosages of gemfibrozil.
Simvastatin is used as an adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum triglyceride concentrations in the treatment of hypertriglyceridemia (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.
Median reductions in total cholesterol concentrations of 25-32%, LDL-cholesterol concentrations of 28-37%, VLDL-cholesterol concentrations of 37-41%, triglyceride concentrations of 29-34%, and non-HDL-cholesterol concentrations of 32-38% have been reported in a subgroup analysis in patients with hypertriglyceridemia who received 40-80 mg daily. Simvastatin 20 mg daily reportedly has produced greater reductions in total and LDL-cholesterol concentrations than gemfibrozil 600 mg twice daily in patients with borderline hypertriglyceridemia; however, reductions in triglyceride concentrations were less pronounced than those reported with usual dosages of gemfibrozil.
Treatment with simvastatin preoperatively to control lipoprotein fractions has been shown to reduce the risk of postoperative thrombocytosis and thrombotic complications following coronary artery bypass grafting (CABG) procedures. Postoperative thrombocytosis (platelet counts exceeding 400,000/ mm) and MI occurred less frequently in simvastatin-treated patients than in those who received placebo (3 and 0%, respectively, versus 81 and 14%, respectively).
Simvastatin has reduced total and LDL-cholesterol concentrations in a few patients with hypercholesterolemia associated with or exacerbated by diabetes mellitus (diabetic dyslipidemia)
(see Secondary Prevention under Uses: Prevention of Cardiovascular Events), cardiac or renal transplantation, or nephrotic syndrome.
Simvastatin also has been shown to improve ejection fraction in cardiac transplant recipients. Improvement in renal cholesterol emboli syndrome was reported in at least one patient who received simvastatin (10-40 mg daily) for 3 months. However, the relationship between simvastatin and these effects is unclear.
For additional information on the role of simvastatin 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.