Best Dx/Best Rx: Diagnosis and Treatment of = Dyslipidemia

From: Subject: Best Dx/Best Rx: Diagnosis and Treatment of Dyslipidemia Date: Wed, 3 Jun 2009 21:18:11 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_016E_01C9E490.CC8128D0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_016E_01C9E490.CC8128D0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx0906.htm Best Dx/Best Rx: Diagnosis and Treatment of = Dyslipidemia

Diagnosis = and Treatment of=20 Dyslipidemia

John D. Brunzell, M.D., F.A.C.P. R. Alan=20 Failor, M.D. University of Washington School of=20 Medicine

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis (Causes of Dyslipidemia)
Best = Tests
Best = Therapy
Best = Evidence

Definition/Key Clinical Features =

A range of disorders that include both = abnormally high=20 and low lipoprotein levels, as well as disorders in the composition of = these=20 particles
Clinically important because of their = contribution to=20 atherogenesis=20
Isolated elevation of LDL cholesterol levels =
Isolated elevation of triglyceride = levels=20
Elevated cholesterol and triglyceride levels = (with=20 small-dense LDL)=20
Low HDL cholesterol levels=20
Atherosclerosis and normal lipid levels =

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Differential = Diagnosis=20 (Causes of Dyslipidemia)

Genetic causes=20
- The metabolic syndrome
- Type 2 diabetes mellitus=20
- Familial combined hyperlipidemia = (FCHL)=20
- Familial hypertriglyceridemia (FHTG)=20
- Familial hypercholesterolemia (FH)=20
- Familial defective apolipoprotein = B-100=20
- Remnant removal disease
Secondary causes=20
- Untreated hyperglycemia=20
- Hypothyroidism=20
- Dyslipidemia secondary to estrogen and = progestin=20 therapy=20
- Nephrotic syndrome=20
- Chronic renal failure=20
- Primary biliary cirrhosis=20
- Alcohol-induced hypertriglyceridemia=20
- Adverse effects of drugs =

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Best Tests = and=20 Goals

Tests=20
- Fasting triglyceride=20
- Total cholesterol=20
- HDL cholesterol
- Calculated LDL cholesterol
Family history=20
Triglyceride levels: elevated when = triglycerides >=20 250 mg/dl
Low HDL cholesterol levels
- In men, < 40 mg/dl
- In women, < 50 mg/dl
LDL cholesterol goals based on CVD risk =
- High to very high risk: goal, < 100 = mg/dl=20
  - Drug therapy when > 100 mg/dl =
- Moderately high risk: goal, < 130 = mg/dl=20
  - Drug therapy when > 130 mg/dl =
- Moderate risk: goal, < 130 mg/dl=20
  - Drug therapy when > 160 mg/dl =
- Lower risk: goal, < 160 mg/dl
  - Drug therapy when > 190 mg/dl=20

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Best=20 Therapy

Hypercholesterolemia/Elevated LDL Cholesterol=20 Levels=20

Reduced consumption of dietary saturated fat = and=20 cholesterol
Lifestyle changes, particularly diet (also = smoking=20 cessation)
- Will reduce LDL cholesterol levels = sufficiently in=20 some patients=20
- Patients with familial forms of high LDL = will require=20 addition of cholesterol-lowering drugs [see Drug Treatment of = Lipid=20 Disorders, below]
Statins [see Drug Treatment of Lipid = Disorders,=20 below]=20
Statins plus bile acid=96binding resins and = drugs that=20 block cholesterol absorption for patients who do not respond to = statins=20 alone=20
- Consider adding nicotinic acid as third drug = when=20 needed. [see Drug Treatment of Lipid Disorders, = below]=20

Hypercholesterolemia/Elevated=20 Triglycerides=20

Fibrates: drugs of choice for patients with = marked=20 hypertriglyceridemia=20
- Will raise HDL cholesterol levels = modestly=20
- Can be used in combination with statins = [see=20 Drug Treatment of Lipid Disorders, below]
Niacin: worsens insulin sensitivity (use care = in=20 patients with type 2 diabetes mellitus)
- Can be used in combination with statins = [see=20 Drug Treatment of Lipid Disorders, below]
Omega-3 fatty acids: found in marine = oils=20
- Might be used when other modalities have = failed to=20 reduce markedly elevated triglyceride levels =

Low HDL Cholesterol Levels=20

Usually accompanies = hypertriglyceridemia=20
Isolated low HDL cholesterol levels (20=9630 = mg/dl) are=20 rare but are a risk factor for cardiovascular disease; treatment is=20 controversial=20
Manage the underlying = hypertriglyceridemia=20
Niacin: can increase HDL cholesterol = levels=20
- Dose: start with 250 mg q.d. with meals; = increase to=20 0.5 g three times a day after meals; slow-release forms available=20 (Niaspan)=20
- Cost/mo: $7; slow-release forms more = expensive=20

Combination = Therapy=20

For use when both LDL cholesterol and = triglyceride=20 levels are elevated and when monotherapy fails to achieve target lipid = and=20 lipoprotein levels=20
Statins + fibrates=20
Statins + niacin=20
Statins + bile-acid sequestrants
Ezetimibe + statins=20
Statins + niacin + an intestinally active = agent=20

Drug Treatment of Lipid Disorders =

Bile Acid=96Binding Resins: for = elevated LDL,=20 normal triglycerides (will increase triglyceride levels)=20

Start with one packet (2 g for colestipol = tabs) b.i.d.,=20 increase over 1=962 wk to desired dose=20
Take other drugs 1 hr before or 4 hr = after=20
May be used with nicotinic acid, statins, or = fibrates=20
Cholestyramine
- Dose: maximum 24 g/day b.i.d. or = t.i.d.=20
- Cost/mo: $69
Colestipol: t.i.d. more effective=20
- Dose: maximum 30 g/day b.i.d. or = t.i.d.=20
- Cost/mo: $305
Colestipol tablets=20
- Dose: maximum 16 g/day
- Cost/mo: $268
Colesevelam: better tolerated than other = resins=20
- Dose: Three 625 mg tablets b.i.d. with meals = or 6=20 tablets/day with a meal; maximum 7 tablets/day=20
- Cost/mo: $190 =

Ezetimibe: can reduce LDL cholesterol by ~ 20% = without=20 increasing plasma triglyceride levels=20

Dose: 10 mg/day=20
Cost/mo: $72

Fibrates: for elevated triglycerides and patients = in whom=20 both LDL and triglycerides are elevated=20

May be used with bile acid=96binding resins or = nicotinic=20 acid=20
Decrease dose with severe renal disease =
Fenofibrate=20
- Dose: 200 mg/day=20
- Cost/mo: $73
Gemfibrozil=20
- Dose: 600 mg b.i.d.
- Cost/mo: $17 =

Niacin: for elevated LDL, triglycerides, or both = with low HDL=20 cholesterol=20

May be used with bile acid=96binding resins or = fibrates=20
- Dose: start with 250 mg q.d. with meals; = increase to=20 0.5 g three times a day after meals; slow-release forms available as = Niaspan=20
- Cost/mo: $7; slow release form more = expensive=20

Statins: for elevated = LDL=20

Possibly useful for patients in whom both LDL = and=20 triglycerides are elevated=20
May be used with bile acid=96binding resins or = ezetimibe=20
Atorvastatin=20
- Dose: start with 10=9620 mg/day; maximum 80=20 mg/day=20
- Cost/mo: $95
Fluvastatin=20
- Dose: start with 20 mg/day; maximum 80 = mg/day=20
- Cost/mo: $68
Lovastatin=20
- Dose: start with 20 mg/day; maximum 80 = mg/day=20
- Cost/mo: $126
Pravastatin: may be used with drugs that are = cleared by=20 hepatic enzymes CYP450, CYP3A4=20
- Dose: start with 40 mg/day; maximum 80 = mg/day=20
- Cost/mo: $120
Resuvastatin=20
- Dose: start with 10 mg/day; maximum 40 = mg/day=20
- Cost/mo: NA
Simvastatin=20
- Dose: start with 20=9640 mg/day; maximum 80=20 mg/day=20
- Cost/mo: $124

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Best Evidence

Carr MC, et al: J Clin Endocrinol Metab 89:2601, = 2004 [PMID=20 15181030]

Executive summary of the third report of the = National=20 Cholesterol Education Program (NCEP) expert panel on detection, = evaluation, and=20 treatment of high blood cholesterol in adults (adult treatment panel = III). JAMA=20 285:2486, 2001 [PMID 11368702]

Grundy SM: Am J Cardiol 90:11i, 2002 [PMID=20 12419477]

Grundy SM, et al: Circulation 110:227, 2004 [PMID = 15249516]

Yusuf S, et al: Lancet 364:937, 2004 [PMID=20 15364185]

April=20 2006