Medication Summary
Classes of medications that are appropriate for the management of major triglyceride elevations include fibric acid derivatives, niacin, and omega-3 fatty acids. High doses of a strong statin (simvastatin, atorvastatin, rosuvastatin) also lower triglycerides, by as much as approximately 50%.
Table 4. Fibric Acid Agents, Omega Acid Ethyl Esters, and Niacin Drug Characteristics [91] (Open Table in a new window)
Drug |
Lipid Effects |
Lipid Effects in Combination with Statin |
Outcomes Data |
Comments |
Bezafibrate |
LDL decrease: 9.6-25% (400 mg) HDL increase: 15-24% (400 mg) Triglyceride decrease: 25-43% (400 mg) |
Further LDL decrease: 1.1% (400 mg) Further HDL increase: 22% (400 mg) Further triglyceride decrease: 31.7% (400 mg) |
Secondary prevention: Prevents composite endpoint of MI and sudden death in a subgroup with triglycerides of 200 mg/dL or higher. No increase in non-CV death |
First-line option for triglyceride >10 mmol/L Option for triglyceride 5-10 mmol/L Option for low HDL Reversible increase in serum creatinine Requires renal dose adjustment Limited data with statins |
Ezetimibe |
LDL decrease: 18% (10 mg/day) HDL increase: 1% (10 mg/day) Triglyceride decrease: 8% |
Further LDL decrease: 25%, as add-on Further HDL increase: 3%, as add-on Further triglyceride decrease: 14%, as add-on |
Prevention of CV events in post-acute coronary syndrome patient when added to statin showed a benefit of reducing the primary endpoint (composite of CV death, MI, unstable angina requiring rehospitalization, coronary revascularization or stroke) by 6.4% vs statin alone In intermediate outcomes studies, ezetimibe did not reduce regression of carotid intima-media thickness (surrogate marker) when added to a statin |
Efficacy studied in combination with atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin Role as statin add-on to reduce LDL if HDL and triglyceride satisfactory |
Fenofibrate |
LDL decrease: 20.6% (145 mg) HDL increase: 11% (145 mg) Triglyceride decrease: 23.5-50.6% (greatest drop in patients with highest triglycerides) (145 mg) |
Further LDL decrease: 0-6% (200 mg) Further HDL increase: 13-17% (200 mg) Further triglyceride decrease: 20-32% (200 mg) |
Prevention of CV events in type 2 diabetes: Did not reduce primary composite outcome (nonfatal MI or CV death). Improved outcomes included nonfatal MI (24% decrease), coronary revascularization (21% decrease), progression to albuminuria, and reduced laser treatments for retinopathy. Nonsignificant increase in risk of CV death. |
First-line option for triglyceride >10 mmol/L (about 1000 mg/dL) Option for triglyceride >500 mg/dL or 5-10 mmol/L Option for low HDL Requires renal dose adjustment Associated with reversible increase in serum creatinine |
Gemfibrozil |
LDL: No effect HDL increase: 6% (1200 mg/day) Triglyceride decrease: 33-50% (greatest drop in patients with highest triglycerides) (1200 mg/day) |
Further triglyceride decrease: 41% Further HDL increase: 9% |
Primary prevention of coronary heart disease Secondary prevention of cardiac events in men with low HDL |
First-line option for triglyceride >10 mmol/L (about 1000 mg/dL) Option for triglyceride >500 mg/dL or 5-10 mmol/L Option for low HDL Requires renal dose adjustment Avoid with statin |
Icosapent ethyl |
LDL decrease: 5% HDL decrease: 4% Triglyceride decrease: 27% |
Further triglyceride decrease: 21.5% (4 g/day), 10.1% (2 g/day) Further LDL decrease: 6.2% (4 g/day) |
Secondary CV risk prevention; REDUCE-IT trial showed primary endpoint (major CV events) occurred in 24.7% of placebo compared with 18.2% of icosapent ethyl treated patients (p = 0.000001) [80] |
Option for triglyceride >500 mg/dL Safe for use with statins Use caution with fish or shellfish allergy |
Niacin |
LDL decrease: 14-17% (Niaspan 2 g/day); 12% (niacin immediate-release 1.5 g/day and Niaspan 1.5 g/day) HDL increase: 22-26% (2 g/day Niaspan); 17% (niacin immediate release 1.5 g/day); 20-22% (Niaspan 1.5 g/day) Triglyceride decrease: 20-50% |
Further LDL decrease: 1-5% (Niaspan 1 g/day); 10% (Niaspan 2 g/day) Further HDL increase: 24% (Niaspan 2 g/day); 15-17% (Niaspan 1 g/day) Further triglyceride decrease: 24% (Niaspan 2 g/day); 12-22% (Niaspan 1 g/day) |
Secondary MI prevention; in combination with a resin, slows progression or promotes regression of atherosclerosis; reduces mortality |
Option for triglyceride >500 mg/dL (about 5 mmol/L) Raises HDL more than any other agent Dose-dependent risk of hyperglycemia (especially in patients with type 2 diabetes) and liver toxicity May increase risk of statin myopathy |
Omega-3 ethyl esters |
LDL increase: 44.5% (4 g/day) HDL increase: 9.1% (4 g/day) Triglyceride decrease: 45% (4 g/day) |
LDL increase: 0.7% (4 g/day) Further HDL increase: 3.4% (4 g/day) Further triglyceride decrease: 29.5% (4 g/day) |
Secondary prevention: Reduces cardiovascular death; sudden death; and combined endpoint of death, nonfatal MI, and nonfatal stroke Secondary prevention in patients with, or at risk for, type 2 diabetes: did not reduce CV events |
Option for triglyceride >500 mg/dL (about 5 mmol/L) Safe for use with statins Associated with an increase in risk for recurrence of symptomatic atrial fibrillation or flutter within first 3 months of therapy Use with caution with fish or shellfish allergy |
Table 5. Statin Drug Characteristics [92] (Open Table in a new window)
Drug |
Potency (average LDL decrease) |
Renal Considerations |
Liver Function Monitoring |
Atorvastatin |
10 mg: 35-39% 20 mg: 43% 40 mg: 50% 80 mg: 55-60% |
No dose adjustment necessary for reduced renal function |
Check liver function tests at baseline and when clinically indicated |
Fluvastatin |
20 mg: 22% 40 mg: 25% 80 mg: 35% (as XL product) |
In severe renal impairment, use daily doses >40 mg with caution |
Check liver function tests at baseline and when clinically indicated |
Lovastatin |
10 mg: 21% 20 mg: 24-27% 40 mg: 30-31% 80 mg: 40-42% (as 40 mg BID) |
If CrCl < 30 mL/min, use daily doses over 20 mg with caution |
Check liver function tests at baseline and when clinically indicated |
Pitavastatin |
1 mg: 31-32% 2 mg: 36-39% 4 mg: 41-45% |
For glomerular filtration rate 15-59 mL/min/1.73 m2, including hemodialysis, initial daily dose is 1 mg, not to exceed 2 mg/day |
Check liver function tests at baseline and when clinically indicated |
Pravastatin |
10 mg: 22% 20 mg: 32% 40 mg: 34% 80 mg: 37% |
In significant renal impairment, start with 10 mg/day |
Check liver function tests at baseline and when clinically indicated |
Rosuvastatin |
5 mg: 45% 10 mg: 46-52% 20 mg: 47-55% 40 mg: 55-63% |
If CrCl < 30 mL/min/1.73 m2 (but not on hemodialysis), starting dose is 5 mg/day, not exceed 10 mg/day Rosuvastatin levels in hemodialysis patients are about 50% higher than levels in normal renal function |
Check liver function tests at baseline and when clinically indicated |
Simvastatin |
5 mg: 26% 10 mg: 30% 20 mg: 38% 40 mg: 29-41% 80 mg: 36-47% |
In severe renal impairment, starting dose is 5 mg daily with close monitoring |
Check liver function tests at baseline and when clinically indicated |
Fibric Acid Agents
Class Summary
Fenofibrate is reported to lower LDL levels more reliably than either clofibrate or gemfibrozil, but none of the drugs in this class should be used for isolated LDL elevations. The fibrates are commonly used to treat hyperlipidemias types IV (high VLDL) and V (high VLDL and chylomicrons), as well as type III dysbetalipoproteinemia (IDL or VLDL remnant disease).
These agents can also be used to treat type IIb mixed hyperlipidemia if used in conjunction with an LDL-lowering medication such as a resin.
Gemfibrozil (Lopid)
Gemfibrozil lowers triglycerides, VLDL, and IDL, but raises HDL. LDL is usually is unaffected but may increase if it is initially low or decrease if it is initially high. This agent increases the activity of lipoprotein lipase, which hydrolyzes triglycerides in triglyceride-rich lipoproteins. Gemfibrozil reduces synthesis of VLDL in the liver and increases the clearance of remnant lipoproteins from blood.
Gemfibrozil is available in generic formulation, most cost-effective fibrate at this time. Its FDA-approved indications are for type IV and V hyperlipidemia (ie, elevations in VLDL only or both VLDL and chylomicrons).
Fenofibrate (Tricor, Lofibra, TriCor, Antara, Triglide)
Fenofibrate is similar to other fibric acid derivatives in triglyceride-lowering and HDL-raising effects. However, this agent differs in that modest LDL-lowering can be expected with greater frequency than with gemfibrozil.
The FDA-approved indications for fenofibrate are for hypertriglyceridemia and hypercholesterolemia, but this difference does not qualify fenofibrate for treatment of isolated LDL elevations. Fenofibrate is taken once a day, which may increase patient compliance. Patients with mild-to-moderate renal disease should receive a reduced dose (about one third of the usual dose), and it is contraindicated in severe renal impairment.
Omega-3 Acids
Class Summary
Prescription omega-3 acids (fish oil) are available and have shown to be effective in lowering very high serum triglycerides (≥ 500 mg/dL).
Icosapent (Vascepa)
Ethyl ester of eicosapentaenoic acid indicated as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia (> 500 mg/dL). It is also indicated as adjunctive therapy for cardiovascular event risk reduction in adults whose TG levels are 150 mg/dL or higher and in whom established cardiovascular disease is present (or in whom, in the absence of established cardiovascular disease, diabetes exists, along with two or more additional cardiovascular disease risk factors). Reduces hepatic VLDL-TG synthesis and/or secretion; enhances TG clearance from circulating VLDL particle; may also increase beta-oxidation, inhibits acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT), decreases lipogenesis in liver, and increases plasma lipoprotein lipase activity. Icosapent does not increase LDL-cholesterol.
Omega-3 fatty acids (Lovaza, Vascazen, Omtryg)
Omega-3-acid ethyl esters were the first prescription omega-3-acid. These are purified fish oil, without heavy metals and polychlorinated biphenyl (PCBs). Content of EPA and DHA vary between each brand.
This agent is theorized to reduce triglyceride synthesis in the liver. EPA and DHA are poor enzyme substrates for triglyceride synthesis in the liver, and they inhibit esterification of other fatty acids. Potential mechanisms of action include acyl CoA:1,2-diacylglycerol acyltransferase inhibition, increased hepatic mitochondrial and peroxisomal beta-oxidation, decreased hepatic lipogenesis, and increased plasma lipoprotein lipase activity.
Omega-3-acid ethyl esters are indicated as adjunctive treatment to dietary changes to reduce very high triglyceride levels (ie, >500 mg/dL).
Clinical trials show significant reduction in non–HDL, triglyceride, total cholesterol, VLDL, and apo B levels from baseline when combined with simvastatin compared with simvastatin and placebo. Monotherapy with omega-3-acid ethyl esters reduces median triglyceride, VLDL, and non–HDL levels from baseline.
Omega-3 carboxylic acids (Epanova)
Omega 3 acids are thought to inhibit acyl CoA:1,2-diacylglycerol acyltransferase. Increased mitochondrial and peroxisomal beta-oxidation in liver , decreased hepatic lipogenesis, and increased activity of plasma lipoprotein lipase activity may also be possible mechanisms. Omega 3 carboxylic acids is the first prescription omega-3 product in free fatty acid form approved in the United States. It is indicated as an adjunct to diet in patients with severe hypertriglyceridemia (ie, TG ≥ 500 mg/dL).
Lipid-Lowering Agents, Other
Class Summary
Niacin (vitamin B-3) inhibits the hepatic secretion of VLDL cholesterol. This agent is effective in most categories of hyperlipidemia. Niacin has been demonstrated to lower LDL cholesterol by 32% (generally, 15-25% decrease), lower triglycerides by 20-50% (≥1.5 g/d decreases triglycerides by as much as 50%), and raise HDL cholesterol by 43%, particularly at higher doses. Niacin lowers lipoprotein (a) levels, which may be of some clinical importance, because lipoprotein (a) levels have been associated with coronary heart disease in numerous epidemiologic studies. The clinical benefit of lowering lipoprotein (a) levels has not been determined.
Whether purchased by prescription or not, niacin costs less than any other lipid-lowering medication. For reasons not clearly understood, changing brands during treatment is more likely to cause hepatotoxicity, occurring more so with time-release than immediate-release niacin. Insulin resistance may increase; nevertheless, niacin is a useful medication in patients with type 2 diabetes. [70]
Niacin (Slo-Niacin, Niaspan, Niacor)
Niacin, or water-soluble vitamin B-3, functions in the body after conversion to nicotinamide adenine dinucleotide (NAD) in the NAD coenzyme system. In gram doses, niacin reduces levels of total cholesterol, VLDL, IDL, LDL, and triglycerides but increases HDL. The magnitude of individual lipid and lipoprotein responses may be influenced by the severity and type of underlying lipid abnormality. Thus, although niacin may increase insulin resistance and worsen glucose control, it is useful for the dyslipidemias common in patients with diabetes. This agent should be taken at bedtime after a low-fat snack and individualized according to patient response.
The slow-release formulation is more hepatotoxic than immediate-release niacin; carefully monitor aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels indefinitely in these patients. Patients strongly advised against switching formulations or brands during treatment. Both prescription and nonprescription formulas are available. Nonprescription brands cost less, but only reliable manufacturers should be recommended. Slo-Niacin is a nonprescription formulation that is available in 250-, 500-, and 750-mg tablets. Prescription extended-release (ER) niacin (Niaspan) is available by prescription in 500-, 750-, and 1000-mg tabs.
At high doses (4-6 g/d), the immediate-release formulation of niacin is less hepatotoxic than the sustained-release (SR) formulation, but it is also less well tolerated by patients due to prostaglandin-mediated flushing, itching, and rash. Therapy is best started at a low dose, such as 100 mg tid pc, and increased gradually (titrated) over several weeks, allowing some patients to accommodate adverse effects. Changing formulation at high doses may increase risk of hepatotoxicity.
Niacor and Nicolar are prescription formulations that, although more expensive than nonprescription brands, may have an advantage in making it less likely that the patient switches brands.
Lipid-Lowering Agents, Statins
Class Summary
3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors are competitive inhibitors of 3-hydroxy-3-methyl Co-A reductase, an enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis, resulting in upregulation of LDL receptors in response to the decrease in intracellular cholesterol. The HMG-CoA reductase inhibitors are indicated for the secondary prevention of cardiovascular events and for the treatment of hypercholesterolemia and mixed dyslipidemia.
HMG-CoA reductase inhibitors are indicated for patients with primary and familial hypercholesterolemia, as well as combined hyperlipidemia, as an adjunct to other lipid-lowering treatments. Their main differences lie in their metabolism and therapeutic half-life and in their drug interactions.
FDA warnings
On March 1, 2012, the US Food and Drug Administration (FDA) issued updates to the prescribing information concerning interactions between protease inhibitors (such as those used to treat hepatitis C or human immunodeficiency virus infection) and certain statin drugs, notably that the combination of these agents taken together may raise the blood levels of statins and increase the risk for myopathy. [57] The most serious form of myopathy, rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal. [57]
Two days earlier, on February 28, 2012, the FDA approved important safety label changes for statins, including removal of routine monitoring of liver enzymes from drug labels. [58] Information about the potential for generally nonserious and reversible cognitive side effects and reports of increased blood sugar and glycosylated hemoglobin (HbA1c) levels were added to the statin labels. In addition, the lovastatin label was extensively updated with new contraindications and dose limitations when this agent is taken with certain medicines that can increase the risk for myopathy. [58]
On June 8, 2011, the FDA recommended limiting the use of the highest approved dose of simvastatin (Zocor) (80 mg) due to the increased risk of myopathy. [59] The agency also required changes to the simvastatin label to add new contraindications (should not be used with certain medications) and dose limitations for using simvastatin with certain medicines. [59]
Atorvastatin (Lipitor)
Fluvastatin
Lovastatin (Mevacor)
Pitavastatin
Pravastatin
Rosuvastatin (Crestor)
Simvastatin (Zocor)
Vytorin
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Eruptive xanthomas on the back of a patient admitted with a triglyceride level of 4600 mg/dL and acute pancreatitis.
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Close-up of eruptive xanthomas.
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Composition of triglyceride (TG)-rich lipoproteins. IDL = intermediate-density lipoprotein; VLDL = very low-density lipoprotein.
-
Lipoprotein lipase (LPL) releases free fatty acids (FFAs) from chylomicrons (chylo) and produces chylomicron remnants that are small enough to take part in the atherosclerotic process. Chol = cholesterol; TGs, TGS = triglycerides.
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Once very low-density lipoprotein (VLDL) has been metabolized by lipoprotein lipase, VLDL remnants in the form of intermediate-density lipoprotein (IDL) can be metabolized by hepatic lipase, producing low-density lipoprotein (LDL), or they can be taken up by the LDL receptor via either apolipoprotein B (apo B) or apo E. Chol = cholesterol; TGs = triglycerides.
Tables
Type |
Serum Elevation |
Lipoprotein Elevation |
I |
Cholesterol and triglycerides |
Chylomicrons |
IIa |
Cholesterol |
LDL |
IIb |
Cholesterol and triglycerides |
LDL, VLDL |
III |
Cholesterol and triglycerides |
IDL |
IV |
Triglycerides |
VLDL |
V |
Cholesterol and triglycerides |
VLDL, chylomicrons |
IDL = intermediate-density lipoprotein; LDL = low-density lipoprotein; VLDL = very low-density lipoprotein. Source: Fredrickson DS, Lees RS. A system for phenotyping hyperlipidaemia. Circulation. Mar 1965;31:321-7. [3] |
||
Classification |
TG level, mg/dL |
Normal triglyceride level |
< 150 |
Borderline-high triglyceride level |
150-199 |
High triglyceride level |
200-499 |
Very high triglyceride level |
>500 |
Source: National Cholesterol Education Program. Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. May 16 2001;285(19):2486-97. [14] |
|
Classification |
LDL Goal, mg/dL |
Non-HDL Goal, mg/dL |
|
CHD and CHD risk equivalent, diabetes mellitus, and the following: |
10-year risk for CHD >20% |
< 100 |
< 130 |
Two or more risk factors and the following: |
10-year risk < 20% |
< 130 |
< 160 |
0-1 risk factor |
< 160 |
< 190 |
|
CHD = coronary heart disease; LDL = low-density lipoprotein; HDL = high-density lipoprotein. Source: National Cholesterol Education Program. Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. May 16 2001;285(19):2486-97. [14] |
|||
Drug |
Lipid Effects |
Lipid Effects in Combination with Statin |
Outcomes Data |
Comments |
Bezafibrate |
LDL decrease: 9.6-25% (400 mg) HDL increase: 15-24% (400 mg) Triglyceride decrease: 25-43% (400 mg) |
Further LDL decrease: 1.1% (400 mg) Further HDL increase: 22% (400 mg) Further triglyceride decrease: 31.7% (400 mg) |
Secondary prevention: Prevents composite endpoint of MI and sudden death in a subgroup with triglycerides of 200 mg/dL or higher. No increase in non-CV death |
First-line option for triglyceride >10 mmol/L Option for triglyceride 5-10 mmol/L Option for low HDL Reversible increase in serum creatinine Requires renal dose adjustment Limited data with statins |
Ezetimibe |
LDL decrease: 18% (10 mg/day) HDL increase: 1% (10 mg/day) Triglyceride decrease: 8% |
Further LDL decrease: 25%, as add-on Further HDL increase: 3%, as add-on Further triglyceride decrease: 14%, as add-on |
Prevention of CV events in post-acute coronary syndrome patient when added to statin showed a benefit of reducing the primary endpoint (composite of CV death, MI, unstable angina requiring rehospitalization, coronary revascularization or stroke) by 6.4% vs statin alone In intermediate outcomes studies, ezetimibe did not reduce regression of carotid intima-media thickness (surrogate marker) when added to a statin |
Efficacy studied in combination with atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin Role as statin add-on to reduce LDL if HDL and triglyceride satisfactory |
Fenofibrate |
LDL decrease: 20.6% (145 mg) HDL increase: 11% (145 mg) Triglyceride decrease: 23.5-50.6% (greatest drop in patients with highest triglycerides) (145 mg) |
Further LDL decrease: 0-6% (200 mg) Further HDL increase: 13-17% (200 mg) Further triglyceride decrease: 20-32% (200 mg) |
Prevention of CV events in type 2 diabetes: Did not reduce primary composite outcome (nonfatal MI or CV death). Improved outcomes included nonfatal MI (24% decrease), coronary revascularization (21% decrease), progression to albuminuria, and reduced laser treatments for retinopathy. Nonsignificant increase in risk of CV death. |
First-line option for triglyceride >10 mmol/L (about 1000 mg/dL) Option for triglyceride >500 mg/dL or 5-10 mmol/L Option for low HDL Requires renal dose adjustment Associated with reversible increase in serum creatinine |
Gemfibrozil |
LDL: No effect HDL increase: 6% (1200 mg/day) Triglyceride decrease: 33-50% (greatest drop in patients with highest triglycerides) (1200 mg/day) |
Further triglyceride decrease: 41% Further HDL increase: 9% |
Primary prevention of coronary heart disease Secondary prevention of cardiac events in men with low HDL |
First-line option for triglyceride >10 mmol/L (about 1000 mg/dL) Option for triglyceride >500 mg/dL or 5-10 mmol/L Option for low HDL Requires renal dose adjustment Avoid with statin |
Icosapent ethyl |
LDL decrease: 5% HDL decrease: 4% Triglyceride decrease: 27% |
Further triglyceride decrease: 21.5% (4 g/day), 10.1% (2 g/day) Further LDL decrease: 6.2% (4 g/day) |
Secondary CV risk prevention; REDUCE-IT trial showed primary endpoint (major CV events) occurred in 24.7% of placebo compared with 18.2% of icosapent ethyl treated patients (p = 0.000001) [80] |
Option for triglyceride >500 mg/dL Safe for use with statins Use caution with fish or shellfish allergy |
Niacin |
LDL decrease: 14-17% (Niaspan 2 g/day); 12% (niacin immediate-release 1.5 g/day and Niaspan 1.5 g/day) HDL increase: 22-26% (2 g/day Niaspan); 17% (niacin immediate release 1.5 g/day); 20-22% (Niaspan 1.5 g/day) Triglyceride decrease: 20-50% |
Further LDL decrease: 1-5% (Niaspan 1 g/day); 10% (Niaspan 2 g/day) Further HDL increase: 24% (Niaspan 2 g/day); 15-17% (Niaspan 1 g/day) Further triglyceride decrease: 24% (Niaspan 2 g/day); 12-22% (Niaspan 1 g/day) |
Secondary MI prevention; in combination with a resin, slows progression or promotes regression of atherosclerosis; reduces mortality |
Option for triglyceride >500 mg/dL (about 5 mmol/L) Raises HDL more than any other agent Dose-dependent risk of hyperglycemia (especially in patients with type 2 diabetes) and liver toxicity May increase risk of statin myopathy |
Omega-3 ethyl esters |
LDL increase: 44.5% (4 g/day) HDL increase: 9.1% (4 g/day) Triglyceride decrease: 45% (4 g/day) |
LDL increase: 0.7% (4 g/day) Further HDL increase: 3.4% (4 g/day) Further triglyceride decrease: 29.5% (4 g/day) |
Secondary prevention: Reduces cardiovascular death; sudden death; and combined endpoint of death, nonfatal MI, and nonfatal stroke Secondary prevention in patients with, or at risk for, type 2 diabetes: did not reduce CV events |
Option for triglyceride >500 mg/dL (about 5 mmol/L) Safe for use with statins Associated with an increase in risk for recurrence of symptomatic atrial fibrillation or flutter within first 3 months of therapy Use with caution with fish or shellfish allergy |
Drug |
Potency (average LDL decrease) |
Renal Considerations |
Liver Function Monitoring |
Atorvastatin |
10 mg: 35-39% 20 mg: 43% 40 mg: 50% 80 mg: 55-60% |
No dose adjustment necessary for reduced renal function |
Check liver function tests at baseline and when clinically indicated |
Fluvastatin |
20 mg: 22% 40 mg: 25% 80 mg: 35% (as XL product) |
In severe renal impairment, use daily doses >40 mg with caution |
Check liver function tests at baseline and when clinically indicated |
Lovastatin |
10 mg: 21% 20 mg: 24-27% 40 mg: 30-31% 80 mg: 40-42% (as 40 mg BID) |
If CrCl < 30 mL/min, use daily doses over 20 mg with caution |
Check liver function tests at baseline and when clinically indicated |
Pitavastatin |
1 mg: 31-32% 2 mg: 36-39% 4 mg: 41-45% |
For glomerular filtration rate 15-59 mL/min/1.73 m2, including hemodialysis, initial daily dose is 1 mg, not to exceed 2 mg/day |
Check liver function tests at baseline and when clinically indicated |
Pravastatin |
10 mg: 22% 20 mg: 32% 40 mg: 34% 80 mg: 37% |
In significant renal impairment, start with 10 mg/day |
Check liver function tests at baseline and when clinically indicated |
Rosuvastatin |
5 mg: 45% 10 mg: 46-52% 20 mg: 47-55% 40 mg: 55-63% |
If CrCl < 30 mL/min/1.73 m2 (but not on hemodialysis), starting dose is 5 mg/day, not exceed 10 mg/day Rosuvastatin levels in hemodialysis patients are about 50% higher than levels in normal renal function |
Check liver function tests at baseline and when clinically indicated |
Simvastatin |
5 mg: 26% 10 mg: 30% 20 mg: 38% 40 mg: 29-41% 80 mg: 36-47% |
In severe renal impairment, starting dose is 5 mg daily with close monitoring |
Check liver function tests at baseline and when clinically indicated |
