| Agent | Mechanism of Action | Dosage | Benefits | Side Effects | Notes |
|---|
|
Colestipol
(Cholestid) | Interrupts bile acid reabsorption requiring bile acid synthesis from cholesterol | 2 scoops bid or tid. (Use bulk form). Begin with 1 scoop in a.m. 30 minutes before meal, increase to bid, then to 2 scoops bid | Nonabsorbed with long-term safety established. LDL cholesterol lowering 10%-15% (LRC-CPPT) | Taste/texture,
bloating, heartburn, constipation, drug interaction (avoidable by
administration of drugs 1 hour before or 4 hours after) and
triglyceride increase | Drug of choice for LDL
cholesterol lowering in children and in women with childbearing
potential. Often used as second line drug with statins because it acts
synergistically to induce LDL receptors. Do not use in patients with
triglycerides >300 or those with GI motility disorders |
|
Colesevelam hydrochloride
(WelChol) | Interrupts bile acid reabsorption requiring bile acid synthesis from cholesterol | Three 625-mg tablets bid (3.8 g total). 3 tablets with breakfast and 3 tablets with dinner | Nonabsorbed with long-term safety established. LDL cholesterol lowering 10%-15% (LRC-CPPT) | Taste/texture,
bloating, heartburn, constipation, drug interaction (avoidable by
administration of drugs 1 hour before or 4 hours after) and
triglyceride increase | Drug of choice for LDL
cholesterol lowering in children and in women with childbearing
potential. Often used as second line drug with statins because it acts
synergistically to induce LDL receptors. Do not use in patients with
triglycerides >300 or those with GI motility disorders |
|
Ezetimibe
(Zetia) | Selectively inhibits the intestinal absorption of cholesterol and related phytosterols | 10 mg qd | Decreases
the delivery of intestinal cholesterol to the liver, thereby reducing
hepatic cholesterol stores and increases the clearance of cholesterol
from the blood rather than inhibiting cholesterol synthesis. Reduces
LDL by 18%, triglycerides by 8%, and apolipoprotein B by 16% | Well tolerated with few adverse reactions similar to placebo | Can
use in combination with statins; however, contraindicated in patients
with active liver disease or elevated LFTs. When used in combination
with statins, yields an additional LDL reduction of 12%, an increase in
HDL of 3%, and a triglyceride reduction of 8% (63). Statin plus ezetimibe yields a total LDL reduction of 25.8% (62; 64). Do not use in combination with resins, fibrates, warfarin, or cyclosporine. May take at the same time as statin (65) |
|
Ezetimibe and simvastatin
(Vytorin) | Combination
of intestinal absorption blocker and statin. Both selectively inhibits
the intestinal absorption of cholesterol and partially inhibits HMG-CoA
reductase | Ezetimibe: 10 mg/simvastatin: 10, 20, 40, or 80 mg qhs | Combination
therapy fosters patient adherence with dosing. Synergistic benefits of
both inhibition of intestinal cholesterol absorption by 54% and statin
LDL lowering of 45%-60% depending on dose | Abnormal LFTs, myositis/myalgias | Contraindicated
in patients with active liver disease or elevated LFTs, pregnant
patients, and nursing mothers. Do not use in combination with
gemfibrozil, other fibrates, >1 g niacin, amiodarone, or verapamil
due to an increased risk of myopathy |
|
Gemfibrozil
(Lopid) | Reduces VLDL synthesis and induces lipoprotein lipase | 600 mg bid | Best
triglyceride-reducing drugs, lowers 50% or more in many patients.
Raises HDL 15%. Reduces CHD events by 24% in patients with low HDL,
high triglycerides (Helsinki, VA-HIT) | Nausea and skin rash | Does
not lower LDL cholesterol reliably, or LDL cholesterol may increase in
one-third of patients. Use in combination therapy with statins
cautiously due to increased incidence of myositis/myalgias. Alters
statin metabolism and causes an increase in statin plasma concentration
(66).
Use with caution in patients with renal insufficiency and gallbladder
disease. Use with repaglinide (Prandin) may cause prolonged severe
hypoglycemia |
|
Fenofibrate
(Tricor, Antara, Triglide, Lipofen, Lofibra) | Reduces VLDL synthesis and induces lipoprotein lipase | Tricor: 48, 145 mg/d
Antara: 43, 87, 130 mg/d
Lofibra: 54, 67, 134, 160, 200 mg/d | Best
triglyceride-reducing drugs, lowers 50% or more in many patients.
Raises HDL 15%. Reduces CHD in patients with low HDL, high
triglycerides (Helsinki, VA-HIT) | Nausea and skin rash. | Does
not lower LDL cholesterol reliably or LDL cholesterol may increase in
one-third of patients. Used in combination therapy in combined
hyperlipidemia. Need to use cautiously with statins, due to increased
myositis/myalgias. Use with caution in patients with renal
insufficiency and gallbladder disease |
|
Atorvastatin
(Lipitor) | Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol
synthesis. This induces LDL receptor formation and removal of LDL
cholesterol from blood | 10-80 mg qd | Well-studied
for safety and efficacy in many trials. Lowers LDL cholesterol 20%-60%
depending on dose and drugs. Raises HDL cholesterol 5%-10%; however, at
higher doses ( 40 mg), can lower HDL cholesterol. Lowers triglycerides 15%-25% | Abnormal liver function tests, myositis/myalgias | Drug
of choice for elevated LDL cholesterol based on safety and efficacy.
Intensive lipid lowering with 80 mg of atorvastatin in patients with
CHD provides significant benefit (percent reduction in CHD events)
compared to 10 mg (67).
Liver function abnormalities less common than previously thought. The 6
statins have different metabolism allowing substitution if side effects
occur. Used in combination with bile acid binding resins to
synergistically lower LDL cholesterol. Used in combination with niacin
and fibrates in patients with combined hyperlipidemia. Use cautiously
in patients on fibrates due to increased risk of myalgia/myositis |
|
Amlodipine and atorvastatin
(Caduet) | | Amlodipine: 10, 20, 40, or 80 mg/atorvastatin: 5 or 10 mg qd | Combination
therapy fosters patient adherence with dosing. Treats both lipid
disorder and hypertension concomitantly using a statin and calcium
channel blocker | Edema, dizziness, headache, flushing, and palpitations | Do not use in patients with congestive heart failure or severe aortic stenosis |
|
Fluvastatin
(Lescol, Lescol XL) | Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol
synthesis. This induces LDL receptor formation and removal of LDL
cholesterol from blood | 20-40 mg qhs
80 mg qhs (XL) | Well
studied for safety and efficacy in many trials. Lowers LDL cholesterol
20%-30% depending on dose and drugs. Raises HDL cholesterol 5%-10%.
Lowers triglycerides 15%-25% | Abnormal LFTs, myositis/myalgias | Drug
of choice for elevated LDL cholesterol based on safety and efficacy.
Liver function abnormalities less common than previously thought. The 6
statins have different metabolism allowing substitution if side effects
occur. Used in combination with bile acid binding resins to
synergistically lower LDL cholesterol. Used in combination with niacin
and fibrates in patients with combined hyperlipidemia. Use cautiously
in patients on fibrates, due to increased risk of myalgia/myositis |
|
Niacin and lovastatin
(Advicor) | Combination product of both extended release niacin (niaspan) and statin (lovastatin) | Niacin: 500 mg/lovastatin: 20 mg
Niacin: 2000 mg/lovastatin: 40 mg
qhs | Combination
therapy fosters patient adherence with dosing. Lowers LDL cholesterol
30%-42%. Raises HDL cholesterol 20%-30%. Reduces triglycerides 32%-44% (68) | Flusing, nausea, glucose intolerance, gout, LFT abnormalities, and elevated uric acid levels. Myositis/myalgias | Drug
of choice for combined hyperlipidemia and for patients who require
simplified dosing. May use a nonenteric coated aspirin taken 1 hour
before evening dose along with a light snack to minimize flushing. Do
not take with hot beverages |
|
Lovastatin
(Mevacor, Altoprev [extended release]) | Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol
synthesis. This induces LDL receptor formation and removal of LDL
cholesterol from blood | 20-80 mg qhs | Well-studied
for safety and efficacy in many trials. Lowers LDL cholesterol 20%-60%
depending on dose and drugs. Raises HDL cholesterol 10%. Lowers
triglycerides 15%-25%. (4S, West of Scotland Coronary Prevention Study
[WOSCOPS], CARE) | Abnormal LFTs, myositis/myalgias | Drug
of choice for elevated LDL cholesterol based on safety and efficacy.
Liver function abnormalities less common than previously thought. The 6
statins have different metabolism allowing substitution if side effects
occur. Used in combination with bile acid binding resins to
synergistically lower LDL cholesterol. Used in combination with niacin
and fibrates in patients with combined hyperlipidemia. Use cautiously
in patients on fibrates, due to increased risk of myalgia/myositis |
|
Pravastatin
(Pravachol) | Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol
synthesis. This induces LDL receptor formation and removal of LDL
cholesterol from blood | 10-40 mg qhs | Well-studied
for safety and efficacy in many trials. Lowers LDL cholesterol 20%-40%
depending on dose and drugs (28% decrease in LDL in the ALLHAT-LLT
trial) (69).
Raised HDL cholesterol 10%. Lowers triglycerides 15%-25%. (West of
Scotland Coronary Prevention Study [WOSCOPS], CARE). Reduces the risk
of major CHD events by 19%-24% in patients with diabetes (LIPID trial) (70) | Abnormal LFT, myositis/myalgias | Drug
of choice for elevated LDL cholesterol based on safety and efficacy.
Liver function abnormalities less common than previously thought. The 6
statins have different metabolism allowing substitution if side effects
occur. Used in combination with bile acid binding resins to
synergistically lower LDL cholesterol. Used in combination with niacin
and fibrates in patients with combined hyperlipidemia. Use cautiously
in patients on fibrates, due to increased risk of myalgia/myositis |
|
Aspirin and pravastatin
(Pravigard PAC) | | Aspirin: 81 or 325 mg/pravastatin: 20, 40, or 80 mg qhs | | | |
|
Rosuvastatin
(Crestor) | Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol
synthesis. This induces LDL receptor formation and removal of LDL
cholesterol from blood | 5-40 mg qhs | Effective
in lowering LDL cholesterol 45%-63% depending on dose and drugs. Raises
HDL cholesterol 8%-14%. Lowers triglycerides 10%-35% (STELLAR trial) (71) | Abnormal LFTs, myositis/myalgias | Newest
of the 6 statins and therefore not as heavily studied in clinical
trials to date; however, numerous industry trials have been conducted.
Do not coadminister with warfarin or gemfibrozil. May be coadministered
with fenofibrate and bile acid-binding resins to synergistically lower
LDL cholesterol |
|
Simvastatin
(Zocor) | Partially
inhibits HMG-CoA reductase, the rate-limiting step of cholesterol
synthesis. This induces LDL receptor formation and removal of LDL
cholesterol from blood | 5-80 mg qhs | Well-studied
for safety and efficacy in many trials. Lowers LDL cholesterol 20%-60%
depending on dose and drugs. Raises HDL cholesterol 10%. Lowers
triglycerides 15%-25%. (4S) | Abnormal LFTs, myositis/myalgias | Drug
of choice for elevated LDL cholesterol based on safety and efficacy.
Liver function abnormalities less common than previously thought. The 6
statins have different metabolism allowing substitution if side effects
occur. Used in combination with bile acid binding resins to
synergistically lower LDL cholesterol. Used in combination with niacin
and fibrates in patients with combined hyperlipidemia. Use cautiously
in patients on fibrates, due to increased risk of myalgia/myositis |
| Niacin | Largely unknown. Reduces hepatic production of B-containing lipoproteins, increases HDL cholesterol production | 500 mg to 1 g tid | Lowers
LDL cholesterol and triglycerides 10%-30%. Most effective drug at
raising HDL cholesterol (25%-35 %). Long term efficacy studies (CDP) | Flushing,
nausea, glucose intolerance, gout, LFT abnormalities, and elevated uric
acid levels. May potentially increase homocysteine levels. | Drug
of choice for combined hyperlipidemia and in patients with low HDL
cholesterol. Extended release preparations limit flushing and LFT
abnormalities. OTC long-acting niacin preparations are not recommended,
as they increase the incidence of hepatotoxicity. Also lowers
lipoprotein (a). Used in combination with statins or bile acid binding
resins in combined hyperlipidemia. To minimize flushing, a nonenteric
coated aspirin can be taken 1 hour before evening dose along with a
light snack. Do not take with hot beverages such as tea or coffee |
Niacin
Niaspan extended release | Largely unknown. Reduces hepatic production of B containing lipoproteins, increases HDL cholesterol production | 500 mg to 2 g qhs | Lowers
LDL cholesterol and triglycerides 10%-30%. Most effective drug at
raising HDL cholesterol (25%-35%). Long term efficacy studies (CDP) | Flushing,
nausea, glucose intolerance, gout, LFT abnormalities, and elevated uric
acid levels. May potentially increase homocysteine levels | Drug
of choice for combined hyperlipidemia and in patients with low HDL
cholesterol. Extended release preparations limit flushing and LFT
abnormalities. Also lowers lipoprotein (a). Used in combination with
statins or bile acid binding resins in combined hyperlipidemia. To
minimize flushing, a non-enteric coated aspirin can be taken 1 hour
before evening dose along with a light snack. Do not take with hot
beverages such as tea or coffee |
|
Omega-3 polyunsaturated fatty acids
(Lovaza) | Inhibits
hepatic triglyceride synthesis and augments chylomicron triglyceride
clearance secondary to increased activity of lipoprotein lipase | 4 g/d (4 tablets) | Effective in controlling triglyceride levels up to 45%. Raises HDL 13% | Dyspepsia, nausea | Can
increase LDL in some patients with hypertriglyceridemia. May increase
bleeding time; therefore, use with caution in patients receiving
anticoagulant therapy |
