INDICATIONS AND USAGE
Therapy with lipid-altering agents should be only one component of multiple risk-factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia.
Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate (see also Table 8 and the NCEP treatment guidelines1).
ADVICOR
ADVICOR (niacin extended-release and lovastatin) is indicated for use when treatment with both NIASPAN and lovastatin is appropriate.
As described in the labeling for Niaspan and lovastatin below, the components of ADVICOR are both indicated for the treatment of hypercholesterolemia. Patients receiving treatment with ADVICOR should be on a standard cholesterol-lowering diet and should continue on this diet during treatment.
NIASPAN (niacin extended-release)
Hypercholesterolemia
NIASPAN is indicated as an adjunct to diet for reduction of elevated TC, LDL-C, Apo B and TG levels, and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Table 7), when the response to an appropriate diet has been inadequate.
Secondary Prevention of Cardiovascular Events
In patients with a history of myocardial infarction and hypercholesterolemia, niacin is indicated to reduce the risk of recurrent nonfatal myocardial infarction.
Hypertriglyceridemia
Niacin is also indicated as adjunctive therapy for treatment of adult patients with very high serum triglyceride levels (Table 7) who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them.
Such patients typically have serum TG levels over 2000 mg/dL and have elevations of VLDL-C as well as fasting chylomicrons (Table 7).
Patients who consistently have total serum or plasma TG below 1000 mg/dL are unlikely to develop pancreatitis.
Therapy with niacin may be considered for those patients with TG elevations between 1000 and 2000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis.
Some patients with TG under 1000 mg/dL may, through dietary or alcohol indiscretion, convert to a pattern with massive TG elevations accompanying fasting chylomicronemia, but the influence of niacin therapy on risk of pancreatitis in such situations has not been adequately studied.
Drug therapy is not indicated for patients with hyperlipoproteinemia, who have elevations of chylomicrons and plasma TG, but who have normal levels of VLDL-C.
Lovastatin
Hypercholesterolemia
Lovastatin is indicated as an adjunct to diet for the reduction of elevated TC and LDL-C levels in patients with primary hypercholesterolemia (Table 7), when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate.
Primary Prevention of Cardiovascular Events
In individuals without symptomatic cardiovascular disease, average to moderately elevated TC and LDL-C, and below average HDL-C, lovastatin is indicated to reduce the risk of:
Myocardial infarction
Unstable angina
Coronary revascularization procedures
Secondary Prevention of Cardiovascular Events
Lovastatin is also indicated to slow the progression of coronary atherosclerosis in
patients with coronary heart disease as part of a treatment strategy to lower TC and LDL-C to target levels.
The National Cholesterol Education Program (NCEP) Treatment Guidelines are summarized below:
TC = total cholesterol; TG = triglycerides; LDL = low-density lipoprotein; VLDL = very low-density lipoprotein; IDL = intermediate-density lipoprotein
= increased or no change
Table 7. Classification of Hyperlipoproteinemias
Type
Lipoproteins Elevated
Lipid Elevations
I (rare)
Chylomicrons
Major
Minor
IIa
LDL
TG
TC
IIb
LDL,VLDL
TC
-
III (rare)
IDL
TC
TG
IV
VLDL
TC/TG
-
V (rare)
Chylomicrons, VLDL
TG
TC
General Recommendations
Prior to initiating therapy with a lipid-lowering agent, secondary causes for hypercholesterolemia (e.g., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded, and a lipid profile performed to measure TC, HDL-C, and TG. For patients with TG < 400 mg/dL, LDL-C can be estimated using the following equation:
LDL-C = TC - [(0.20 x TG) + HDL-C]
For TG levels > 400 mg/dL, this equation is less accurate and LDL-C concentrations should be determined by ultracentrifugation. Lipid determinations should be performed at intervals of no less than 4 weeks and dosage adjusted according to the patient's response to therapy. The NCEP Treatment Guidelines are summarized in Table 8.
Table 8.
NCEP Treatment Guidelines:
LDL-C Goals and Cutpoints for Therapeutic Lifestyle Changes and Drug Therapy in Different Risk Categories
Risk Category
LDL Goal(mg/dL)
LDL Level at Which to Initiate Therapeutic Lifestyle Changes(mg/dL)
LDL Level at Which toConsider DrugTherapy (mg/dL)
CHD or CHDrisk equivalents(10-year risk >20%)
<100
100
130(100-129:drug optional)
2+ Risk factors(10-year risk 20%)
<130
130
10-year risk 10%-20%:
130
10-year risk <10%:
160
0-1 Risk factor
<160
160
190(160-189:LDL-loweringdrug optional)
CHD, coronary heart disease
Some authorities recommend use of LDL-lowering drugs in this category if an LDL-C level of <100 mg/dL cannot be achieved by therapeutic lifestyle changes. Others prefer use of drugs that primarily modify triglycerides and HDL-C, e.g., nicotinic acid or fibrate. Clinical judgement also may call for deferring drug therapy in this subcategory.
Almost all people with 0-1 risk factor have 10-year risk <10%; thus, 10-year risk assessment in people with 0-1 risk factor is not necessary.
After the LDL-C goal has been achieved, if the TG is still 200 mg/dL, non-HDL-C (TC minus HDL-C) becomes a secondary target of therapy.
Non-HDL-C goals are set 30 mg/dL higher than LDL-C goals for each risk category.