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Introduction
Hypercholesterolemia- Why do we Care? 1. Affects 65 Million U.S. Adults 2. Independent Risk Factor for CHD 3. CHD #1 Killer in U.S. 4. My fiance has it
1. ONLY worry about LDL 2. If LDL is high- Put ALL Patients ONLY on a Statin for life 3. Pat yourself on the back when LDL is decreased and forget about your patients who die of heart attacks despite being on a statin
Yes
Yes or No
*Coronary heart disease or peripheral vascular disease (including symptomatic carotid artery disease). ** Other risk factors for coronary heart disease (CHD) include: age (males > 45 years, females > 55 years or premature menopause without estrogen replacement therapy); family history of premature CHD; current cigarette smoking; hypertension, confirmed HDL-C < 35 mg/dL (< 0.91 mmol/L); and diabetes mellitus. Subtract 1 risk factor if HDL-C is > 60 mg/dL (> 1.6 mmol/L).
ATP III Classification of LDL, Total, and HDL Cholesterol (JAMA- May 16, 2001)
LDL Cholesterol Primary Target of Therapy
1. <100 Optimal 2. 100-129 Near optimal/above optimal 3. 130-159 Borderline high 4. 160-189 High 5. >190 Very high
number of patients that should be on cholesterol-lowering medication by 300% from 12 million to 36 million Threshold for HDL to 40 mg/dl (from 35) Threshold for Elevated Triglycerides Risk factor status of Diabetics to equal that of someone with CHD
New Treatment Category: Metabolic syndrome= Obesity, HTN, Glc, TGs, HDL
Recommended initial test= Complete lipid panel Total cholesterol, LDL, HDL, and TGs
Combination therapy highlightedStatin +Niacin, and Statin + BAS
2. Statins
a. Great at lowering LDL levels b. Not much affect on Lipoprotein(a), HDL, or small dense LDL, and minor effects on Triglycerides
Who Cares?
The National Cholesterol Educational Panel (NCEP) Cares and in 1993Began focusing more on other major lipids in addition to LDL 1 This In-Depth Study Revealed a Plethora of Information related to CHD Risk
VLDL Carries triglycerides to peripheral cells High levels may be associated with increased CHD risk2 LDL Carries cholesterol to cells High levels linked to increased CHD risk Primary target of cholesterol-reducing therapy3 HDL Removes cholesterol from cells High HDL considered protective against CHD HDL >60 mg/dL decreases CHD risk1 Lipoprotein(a) A complex of LDL and apolipoprotein(a) Prevents LDL from being taken up by the Liver Elevated Lp(a) is an independent risk factor for premature CHD4 Triglycerides A neutral fat stored in adipose cells Positively correlated with risk for CHD1
25% of Men with a FH of CHD: 1st Sign of Heart Disease is Sudden Death 50% of arteriosclerosis cant be explained by standard risk factors (smoking, diet, lifestyle, and high cholesterol) 80% of people who develop CHD have the same basic cholesterol numbers as those who dont have CHD
LDL sub-classes- small dense (IIIa and IIIb) vs large buoyant HDL sub-classes- HDL2b Lp(a) Homocysteine Insulin C-reactive protein
HDL
Has been shown to be Cardioprotective in the Framingham Heart Study, and in retrospective analyses of intervention trials such as the Coronary Primary Prevention Trial and the Multiple Risk Factor Intervention Trial 5-7 The data were consistent with a 2% to 3% decrease in CHD risk for each 1 mg/dL increase in HDL, after adjustment to control for other risk factors.
8 HDL
The importance of raising HDL to reduce morbidity and mortality was clearly confirmed with the publication August 1999 in the NEJM of the findings of the landmark Veterans Administration High Density Lipoprotein Intervention Trial (VA-HIT) clinical outcome study.
Niacin
Increases HDL by up to 26% Decreases LDL by up to 17% Decreases TGs by up to 35% Decreases Lp(a) by up to 27%
Increases HDL better than ANY other medication and increases HDL2b the most
Only drug that has been shown to switch subclasses of LDL from small dense (IIIa and IIIb), to large buoyant (Pattern B to Pattern A)
Decreases Lp (a) the best of any medication
Main Reason- Flushing Difficult Dosing (TID) Its too cheap (No $$$ for Drug companies)
Niaspan is the Only Once-Daily Clinically Tested Niacin Product Approved by the FDA for the Treatment of Cholesterol and Lipid Disorders
HydroGel Programmed-Release formulation
Minimizes flushing Once-at-Night dosing Mean liver enzyme levels remain within normal limits9,10,11
Decreased Flushing
1. Niaspan has been shown to decrease flushing episodes by 78% vs Immediate-Release Niacin10
Flushing Tips
When beginning or increasing dose- take 400mg Ibuprofen (or equivilant Naproxen or Aspirin) 30 min before Niaspan Avoid Hot drinks, Hot shower, or spicy foods 1 hr before or anytime after Niaspan dosing Eat a low-fat snack with Niaspan Take right before going to bed
Niaspan
(Continued)
2. Easy Once a Day Dosing at Bedtime (Most Free Fatty Acid Mobilization Occurs Nocturnally) 3. Minimal to No Increase in LFTs11
Combination Therapy
No cases of myopathy and <1% with LFTs 9% of patients discontinued due to Flushing
Large RCT
Patient population n=1 (My girlfriend) Treatment= 1. 1st month Slo-Niacin (OTC extended release) titrated up to 1 gram over 1 month 2. 2nd month Niaspan 500mg-2.5wks,1gram-1.5wks 3. 3 months Niaspan 1gram qhs (Currently on 1gm Niaspan qhs)
Amazing Results
Lizs Results
3/09/01 4/23/01 5/24/01 8/23/01 Total Cholesterol LDL 276 228 208 203
206
154
137
130
HDL
40
36
187
41
147
56
83
Triglycerides 150
CHD Risk
Decreased from:
Summary
LDL is not the only Lipoprotein that should be considered for CHD Risk- HDL, TGs, Lp(a) should be evaluated and consideration should be given to LDL/HDL sub-class testing with a strong FH of sudden cardiac death Niaspan is close to a Magic Bullet by moving ALL Lipoproteins in the right direction, especially HDL, and doing positive things in areas we are not currently testing like Lp(a) and LDL/HDL subclasses
Advicor- is being shown to have phenomenal effects on the Lipid profile and (pending FDA approval in the second half of 2001) will become a formidable weapon in the war against CHD
References
1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel || ). JAMA. 1993;269:3015-3023 2. Phillips NR, waters D, Havel RJ. Plasma lipoproteins and progression of coronary artery disease evaluated by angiography and clinical events. Circulation 1993;88:2762-2770 3. NIH Consensus Development Panel on Triglyceride, High-Density Lipoprotein, and Coronary Heart Disease. Triglyceride, high-density lipoprotein and coronary heart disease. JAMA. 1993;269:505-510. 4. Bostom AG, Cupples LA, Jenner JL, et al. elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger: a prospective study. JAMA. 1996;276:544-548. 5. Lipid research clinics program. The lipid research clinics clinics coronary primary prevention trial results. 1 Reduction in incidence of coronary heart disease. JAMA 1984;251:351-364 6. Multiple risk factor intervention trial research group: Multiple risk factor intervention trial: Risk factor changes and mortality results. JAMA 1982;248:1465-1477 7. Gordon T, Castelli WP, Hjortland MC, et.al High density lipoprotein as a protective protective factor against coronary heart disease: The Framingham Study. Am J MED 1977;62:707-714
References (2)
8. Rubins HB,Robins SJ, Collins D, Fve CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of highdensity lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999 Aug 5;341(6):410-416. 9. Morgan JM, Capuzzi DM, Guyton JR, et al. Treatment effect of Niaspan, a controlled-release niacin, in patients with hypercholesterolemia: a placebocontrolled trial. J Cardiovasc Pharmacol Therapeut. 1996;1:195-202 10. Knopp RH, Alagona P, Davidson M. at al. Equivalent efficacy of a time-release form of niacin (NIASPAN) given Once-a-Night versus plain naicin in the managment of hyperlipidemia metabolism 1998;47:1097-1104 11. Goldberg A, Alagona P, Capuzzi DM, et al. Multiple dose efficacy and safety of an extended-release form of niacin in the management of Hyperlipidemia. AM J Cardiol 2000;85:1100-1105. 12. Guyton JR, Goldberg AC, Kreisberg RA, et al effectivness of once nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia; AM J Cardiol 1998;82 737-743. 13. Guyton JR, Capuzzi DM. Treatment of hyperlipidemia with combined niacinstatin regimens. AM J Cardiol 1998;82:824-844. 14. Wolfe ML, Vartanian SF, Ross JL, Bansavich LL, Mohler ER 3rd, Meagher E, Friedrich CA, Rader DJ. Safety and effectiveness of Niaspan when added sequentially to a statin for treatment of dyslipidemia. Am J Cardiol. 2001 Feb 15;87(4):476-9, A7. 15. Kayshyap ML, Evans R, Simmons PD, Kohler RM, McGovern ME. New combination niacin/statin formulation shows pronounced effects on major lipoproteins and is well-tolerated. J Am Coll Cardiol 2000;35(suppl A):326A.
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Professionals
The Guidelines Related Tools
ATP III Executive Summary ATP III Slide Show ATP III Full Report (coming soon) Palm OS Interactive Tool ATP III At-A-Glance: Quick Desk Reference 10-year Risk Calculator (online version)
Download our ATP III Cholesterol Management Implementation Tool for Palm OS
The Palm OS program for application 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) is now available. This interactive guideline tool will assist the clinician in implementing the ATP III Cholesterol Guidelines at the point of care. The program also contains usable information from ATP III including: ATP III classification of lipid levels. ATP III CHD risk assessment. Therapeutic Lifestyle Changes (TLC). Drug therapy for lipid lowering. Information on the metabolic syndrome. Issues for special populations.
Liz before
Niaspan
Liz after
Niaspan