TOC   |  DRUGS |   ACP Drug Resource | Medline Drugs Info Site    
Hyperlipidemia                   http://www.lipidhealth.org/  |  http://www.apollolipids.org/  NCEP  ATP III

Drug Rx for Hyperlipidemia     See Drug Rx for Hyperlipidemia 2008  

Use knowledge of drug actions and interactions to adapt single and combination drug therapy to specific lipid abnormalities.

Select drugs which have effects on several lipoprotein fractions, such as:

 Drug Rx for Hyperlipidemia                See  Hyperlipidemia Rx 2008  (ACP) |    Hypertryglyceridemia 2007  
Statin Meds:  (* In CRF pt with GFR<30 or dialysis - give 1/2 the max dose twice daily)
  • Lescol (Fluvastatin) 20, 40 mg cap / day; new Lescol-XL 80 mg 1/day (Range 20-80 mg/d)
  • Lipitor (Atorvastatin) 10 , 20, 40 mg tab (Range 10-80 mg/d)
  • Mevacor (Lovastatin) 10-20-40 mg tab. Dose 10-80-mg/day (Range 10-80 mg/d)
  • Pravachol (Pravastatin) 10- 20 mg tab. Dose 10-20 mg/day  (Range 10-40 mg/d)
  • Zocor (Simvastatin) 5, 10, 20, 40, 80 mg tab: Dose 10-40 mg/day  (Range 10-80 mg/d)
  • Crestor (Rosuvastatin)  5- 40 mg/day
  • Advicor (Niacin 500 mg/Lovastatin 20 mg tablet or Niacin1000 mg/Lovastatin 20 mg table)
  • Vytorin (Ezetimibe/Zetia + simvastatin/Zocor) 10/10, 10/20. 10/40, 10/80 tablet daily
  • Baycol (Cerivastatin) 0.2, 0.3 mg tab - discontinued 8-8-2001
         Aug. 8, 2001 — A cholesterol-lowering drug taken by 700,000 Americans — Bayer Pharmaceutical’s Baycol  (Cerivastatin) — was pulled off the market Wednesday because of muscle destruction linked to 31 U.S. deaths and at least nine more fatalities abroad.
  • Pitavastatin 1,2, 4 mg tablet
    FDA approves cholesterol drug pitavastatin August 4, 2009 | Michael O'Riordan, Rockville, MD - The US Food and Drug Administration has approved pitavastatin (Livalo, Kowa Pharmaceuticals America), a new cholesterol-lowering drug for the primary treatment of hypercholesterolemia and combined dyslipidemia [1].
    Pitavastatin is the newest addition to the drug class, joining atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, and fluvastatin on the crowded statin market. The drug is expected to launch in the US in early 2010 and will be available in three low dosages: 1 mg, 2 mg, and 4 mg. It is has been available in Japan since 2003 and is also available in South Korea, Thailand, and China.
    According to the FDA, the drug was approved on the basis of results from five clinical trials showing that pitavastatin was as safe and effective as other statins on the market. A press release issued by the company notes that the studies showed the drug to be particularly effective in special populations, including the elderly, patients with diabetes, and those at higher cardiovascular risk [2].
Niacin 250-500 mg tab 1-2 tab tid    REF:  ACP PIER 2008

Benefits: Lowers LDL cholesterol and triglycerides 10%-30%. Most effective drug at raising HDL cholesterol (25%-35 %). Long term efficacy studies (CDP)

Side Effects: Flushing, nausea, glucose intolerance, gout, LFT abnormalities, and elevated uric acid levels. May potentially increase homocysteine levels.

Notes: 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.

   
Resin Meds:
  • Questran (Cholestyramine) 1-3 scoops 1-2x/day
  • Colestid 1-3 scoops  (5 gm/scoop)  1-2x/day  
  • Welchol (Colesevelam) 625 mg tablet 3 tab bid  
            Colesevelam hydrochloride is an oral, non-absorbed hydrogel polymer; it binds with bile acids in the intestine thereby impeding their reabsorption. It is used for the treatment of hypercholesterolemia. When used as a single agent, colesevelam reduces LDL-cholesterol by roughly 15—20%, compared with 30% reductions typically seen with HMG-CoA reductase inhibitors as monotherapy. The effects of colesevelam on LDL-cholesterol are synergistic with those of HMG-CoA-reductase inhibitors. Colesevelam was FDA approved on May 26, 2000.

Colestid (Colestipol)

  • Dose: 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
  • Benefits: Nonabsorbed with long-term safety established. LDL cholesterol lowering 10%-15% (LRC-CPPT)
  • Side Effects: Taste/texture, bloating, heartburn, constipation, drug interaction (avoidable by administration of drugs 1 hour before or 4 hours after) and triglyceride increase
  • Notes: 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)

  • Dose: Three 625-mg tablets bid (3.8 g total). 3 tablets with breakfast and 3 tablets with dinner
  • Benefits, Side Effects, & Notes: same as for Colestid above

   
Ezetimibe (Zetia) 10 mg
is a novel lipid-lowering agent that is absorbed systemically but that acts by inhibiting intestinal absorption of cholesterol. The drug recently was approved by the FDA, both for monotherapy and for combination therapy with statins. In this multicenter randomized trial, sponsored by the manufacturer of ezetimibe, researchers studied the effects of ezetimibe alone, simvastatin alone, and combination therapy.
At 12 weeks, LDL cholesterol reduction was 1% with placebo, 18% with ezetimibe alone, 27% to 44% with various doses of simvastatin alone, and 44% to 57% with combination therapy. Compared with simvastatin alone, combination therapy significantly improved LDL cholesterol, HDL cholesterol, and triglyceride levels. Combination therapy generally was tolerated well.    J Am Coll Cardiol 2002 Dec 18; 40:2125-34.

Vytorin (Ezetimibe/Zetia + simvastatin/Zocor) 10/10, 10/20. 10/40, 10/80 tablet daily  

   
Fibrate Meds:
  • Lopid (Gemfibrozil) 600 mg bid
  • Tricor (Fenofibrate) 54 mg, 145 mg, 160 mg 1 tablet daily for hyper-triglyceremia
    Lofibra (Fenofibrate)     54 mg tab, 67 mg cap, 134 mg cap, 160 mg cap, 200 mg cap one daily
    Antara: 43, 87, 130 mg/d

Benefits: 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)

Side Effects: Nausea and skin rash

Notes: 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

Tricor: 48, 145 mg/d

Antara: 43, 87, 130 mg/d

Lofibra: 54, 67, 134, 160, 200 mg/d

   
Current Combination Lipid Therapy & Side Effects:

For Elevated LDL & Normal Trig < 200 mg/dL:

For Elevated LDL & Elevated Trig 200-500 mg/dL

  • Statin + Niacin
    May have myopathy & hepatitis
  • Statin + Fibrate
    May have myopathy !!!
  • Niacin + Resin
  • Niacin + Fibrate

Indications for combination therapy

  • Greater effect on a single lipoprotein abnormality
  • Control multiple lipid and lipoprotein abnormalities
  • Achieve target lipid and lipoprotein goals at reduced cost
  • Reduce the likelihood of side effects due to smaller doses of individual drug that are administered

   
Treatment to increase HDL levels:  
REF: JAMA Aug 15, 2007;298 (7): 786
  • Aerobic exercise
  • Weight loss
  • Diet rich in poly-unsaturated fats
  • Drugs:
  • Niacin (Nicotinic acid) 1-2 gm 2-3x/day - can increase HDL by 20-30%
  • Statins - can increase HDl by 5-15%
  • Gemfibrozil (Lopid 600 mg bid) & Fenofibrate  (Tricor 48-145 mg daily)
  • Rimonabant 5-20 mg/day

   

Treatment to lower Triglyceride:

Recommendations for Omega-3 Fatty Acid Intake:

  • Patients who need to lower triglycerides 2 to 4 grams of EPA+DHA per day provided as capsules under a physician’s care.
  • Consume about 1 g of EPA+DHA per day, preferably from fatty fish. EPA+DHA in capsule form could be considered in consultation with the physician.  Eat a variety of (preferably fatty) fish at least twice a week. Include oils and foods rich in alpha-linolenic acid (flaxseed, canola and soybean oils; flaxseed and walnuts).

NCEP GUIDELINES   
( JAMA. Jan.5,2000;283:94-98 , JAMA. 1993;269:3015-3023.; )
According to NCEP guidelines, LDL-C–lowering therapy should be initiated in most patients with CHD if the LDL-C level is more than 100 mg/dL. These guidelines indicate that a reasonable goal of therapy is to reduce LDL-C to 100 mg/dL or less. As defined by NCEP, therapy always means dietary therapy and may or may not include drug therapy. Maximal dietary therapy should always be used for patients whose LDL-C level is more than 100 mg/dL. If the LDL-C level at baseline is 130 mg/dL, drug therapy generally should be started.   According to the NCEP, if the LDL-C level is 100 to 129 mg/dL (2.59-3.34 mmol/L), dietary therapy and other life habit modifications, especially physical activity and weight control, should be used; whether to use drug treatment is a decision for the physician to make based on clinical judgment. The rationale for an LDL-C goal of 100 mg/dL or less in secondary prevention is based on evidence including data from epidemiological, angiographic, and clinical end-point studies.

Initial Classification of Hyperlipidemia based on total Cholesterol and HDL
Total Cholesterol
<200 mg/dL       - Desirable Blood Cholesterol
200-239 mg/dL  - Borderline-High Blood Cholesterol
=>240 mg/dL     - High Blood Cholesterol

HDL-Cholesterol
HDL  <35mg/dL  - Undesirably Low HDL

LDL-cholesterol = total cholesterol - HDL-cholesterol - (triglyceride/5).
LDL  >160 mg/dL as "high-risk LDL-cholesterol,"
LDL    130-159 mg/dL as "borderline-high-risk LDL-cholesterol," and
LDL  <130 mg/dL as "desirable LDL-cholesterol."

LDL  <100 mg/dL as desirable in diabetic, and CAD patients

Table - Treatment Decisions Based on LDL-Cholesterol

Dietary Therapy
.      Initiation Level          LDL Goal    
Without CHD & <2 risk factors 160 mg/dL <160 mg/dL
Without CHD & with 2 or more risk factors 130 mg/dL <130 mg/dL
With CHD >100 mg/dL <100 mg/dL

Drug Treatment
.      Initiation Level          LDL Goal    
Without CHD & <2 risk factors 190 mg/dL <160 mg/dL
Without CHD & with 2 or more risk factors 160 mg/dL <130 mg/dL
With CHD >130 mg/dL <100 mg/dL

* In men under 35 years of age and premenopausal women with LDL-cholesterol levels 190-219 mg/dL, drug therapy should be delayed except in high-risk patients such as those with diabetes.
** In CHD patients with LDL-cholesterol levels 100-129 mg/dL, the physician should exercise clinical judgment in deciding whether to initiate drug treatment.

     

The 2001 ATP (Adult Treatment Panel) III clinical definition of Metabolic syndrome requires the presence of 3 or more of the following:

  1. Abdominal obesity with Waist >40 inches (>102 cm) in men, >35 inches (>88 cm) in women
  2. Triglyceride >150 mg/dL
  3. HDL <40 mg/dL in men, <50 mg/dL in women
  4. BP >130/95
  5. FBS >110 mg/dL

The National Cholesterol Education Program-Adult Treatment Panel III (NCEP-III) recommended a new classification, the metabolic syndrome, for persons thought to be at high risk for vascular disease risk. Persons with three or fewer of the five factors (increased waist circumference, triglycerides, low high-density lipoprotein [HDL] cholesterol, high blood pressure, or impaired fasting glucose) are considered to have the syndrome. (Adapted from the Executive Summary of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III] [13 - JAMA Vol. 285 No. 19, May 16, 2001 ]).

           

2008

Adams LA, Lindor KD. Treatment of hyperlipidemia in nonalcoholic fatty liver disease: Fat for thought. Indian J Gastroenterol [serial online] 2004 [cited 2008 Nov 14];23:127-8.  http://www.indianjgastro.com/text.asp?2004/23/4/127/12404

In this issue of the Journal, Hatzitoloios and colleagues enrolled a select group of 72 non-diabetic NAFLD patients with hyperlipidemia, in an open-label, uncontrolled study of 24 weeks' duration.[9] Patients with hypertriglyceridemia (n=23) were given omega-3 fatty acids (5 mL, thrice daily), patients with predominant hypercholesterolemia (n=28) were given atorvastatin (20 mg daily), and obese dyslipidemic patients (n=28) were prescribed orlistat (120 mg, thrice daily). Endpoints were safety and efficacy as judged by change in aminotransferases and resolution of fatty infiltration on liver ultrasound. After 24 weeks, all patients had reductions in triglyceride and cholesterol levels. Similarly, all patients had significant reductions in aminotransferase levels, although only the group receiving orlistat had complete normalization in all patients. This was also the only group that lost a significant amount of weight over the treatment period. When ultrasonography was repeated at the end of treatment, a normal liver echopattern was observed in 86% of patients receiving orlistat, 61% of those on atorvastatin, and 35% of those taking omega-3 fatty acids.

These promising results have also been echoed in a few other smaller pilot studies. A diet high in polyunsaturated fatty acids has been shown to be associated with liver enzyme improvement in obese subjects with fatty liver.[10] Similarly, atorvastatin and orlistat have improved liver enzymes as well as liver steatosis in a handful of patients over 6-12 months.