N3-173 Global Risk 29/10/2013 15:20:48 Lipid Lowering Strategies www.cardiowellness.blogspot.com Becky K. Captain, RN, MSN, CLS, BC, FNP Becky K. Captain, RN, MSN, CLS, BC, FNP-C Clinical Lipid Specialist Clinical Lipid Specialist Conflict of Interest Disclosure & Resolution • Consultant for Good Things Health Consultant for Good Things Health • Speaker for Abbott and Forest Pharmaceuticals Speaker for Abbott and Forest Pharmaceuticals Objectives • Know NCEP ATP III guidelines Know NCEP ATP III guidelines • Know how to lower LDL through diet and Know how to lower LDL through diet and medications medications • Know how to lower non Know how to lower non- HDL cholesterol HDL cholesterol adnt adnt triglycerides through diet and medication triglycerides through diet and medication
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N3-173 Global Risk29/10/2013 15:20:48
Lipid Lowering Strategies
www.cardiowellness.blogspot.com
Becky K. Captain, RN, MSN, CLS, BC, FNPBecky K. Captain, RN, MSN, CLS, BC, FNP--CCClinical Lipid SpecialistClinical Lipid Specialist
Conflict of Interest Disclosure & Resolution
•• Consultant for Good Things HealthConsultant for Good Things Health
•• Speaker for Abbott and Forest PharmaceuticalsSpeaker for Abbott and Forest Pharmaceuticals
Objectives
•• Know NCEP ATP III guidelinesKnow NCEP ATP III guidelines
•• Know how to lower LDL through diet and Know how to lower LDL through diet and medicationsmedications
•• Know how to lower nonKnow how to lower non--HDL cholesterol HDL cholesterol adntadnttriglycerides through diet and medicationtriglycerides through diet and medication
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“A Whole New World”
Cath Lab Sensation 16 MS CT
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How Much of the Patient Are We Treating?
0.0002 m2
1,000 m2
70 KG Male
= 1 / 5,000,000
Primary & Secondary Goals of Lipid ManagementAccording to NCEP
LDLLDL--CC•• Primary target after TLCPrimary target after TLC•• LDLLDL--C <100 mg/C <100 mg/dLdL
identified as optimal for identified as optimal for pts. w/ CHD or CHD risk pts. w/ CHD or CHD risk equivalent equivalent
•• NCEP recommends NCEP recommends optional LDLoptional LDL--C goal of C goal of <70 mg/<70 mg/dLdL for high risk for high risk pts.pts.
NonNon--HDLHDL--CC•• Secondary target if TG are Secondary target if TG are
200200--499 mg/499 mg/dLdL and LDLand LDL--C C goal is metgoal is met
•• NonNon--HDLHDL--C = Total C = Total Cholesterol minus HDLCholesterol minus HDL--CC
•• NonNon--HDLHDL--C represents all C represents all atherogenicatherogenic particlesparticles
•• NonNon--HDLHDL--C goal is 30mg/dL C goal is 30mg/dL higher than LDLhigher than LDL--C goalC goal
•• Increasing HDLIncreasing HDL--C will lower C will lower NonNon--HDLHDL--CC
NCEP ATP III Final Report, Circulation 2002; 106 3143-3421
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Comparison of LDL Cholesterol and Non-HDL Cholesterol Goals
LDL-C Goal(mg/dL)Risk Category
Non-HDL-C Goal (mg/dL)
<100(optional <70)
CHD and CHD Risk Equivalent(10-year risk for CHD >20%)
<130(optional <100)
<130(optional <100)
Multiple (2+) Risk Factors and10-year risk <20%
<160(optional <130)
<1600–1 Risk Factor <190
NCEP ATP III Final Report, Circulation 2002; 106 3143-3421
CHD Risk Equivalents
•• >20% 10>20% 10--year risk of CHD year risk of CHD (Framingham projections)(Framingham projections)
•• DiabetesDiabetes
•• Other forms of clinical atherosclerotic Other forms of clinical atherosclerotic disease:disease:
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
Peripheral Arterial Disease (PAD)
•• Studies of pts w/ PAD support the concept that Studies of pts w/ PAD support the concept that
PAD, regardless of diagnosis PAD, regardless of diagnosis (ABI, lower limb (ABI, lower limb
blood flow studies, or clinical symptoms) blood flow studies, or clinical symptoms) is a CHD is a CHD
risk equivalentrisk equivalent
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
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Abdominal Aortic Aneurysm (AAA)
•• Study population:Study population: 300 men and 43 women (aged 45300 men and 43 women (aged 45 89) 89) operated on for AAA, separated into 4 groups based on operated on for AAA, separated into 4 groups based on preoperative CHD history and ECGpreoperative CHD history and ECG
1.9% in persons with no symptoms, no prior history of CHD, and 1.9% in persons with no symptoms, no prior history of CHD, and normal ECG (31%)normal ECG (31%)
2.0% in persons with no symptoms, but previous MI by ECG 2.0% in persons with no symptoms, but previous MI by ECG (33%)(33%)
3.9% in persons with angina/prior MI (30%)3.9% in persons with angina/prior MI (30%)
•• Because the rate of CHD events is at least twice that of CHD Because the rate of CHD events is at least twice that of CHD mortality, patients with no previous history of CHD events wouldmortality, patients with no previous history of CHD events wouldfall into the CHD risk equivalent categoryfall into the CHD risk equivalent category
Hertzer NR. Ann Surg 1980;192:667-673.
•• Mayo Asymptomatic Carotid Atherosclerosis StudyMayo Asymptomatic Carotid Atherosclerosis StudySubjectsSubjects
158 patients, 40% with history of CAD, 15% diabetic158 patients, 40% with history of CAD, 15% diabeticDisease severityDisease severity
Asymptomatic Asymptomatic stenosisstenosis ≥≥ 50%50%Trial stopped because of high MI and TIA event rate Trial stopped because of high MI and TIA event rate in surgical arm secondary to cessation of medical in surgical arm secondary to cessation of medical therapy (aspirin)therapy (aspirin)
Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273:1421-1428.
Carotid Artery Disease: Asymptomatic
0
10
20
30
40
50
Haffner SM et al. N Engl J Med 1998;339:229-234.
Incidence of MI during a 7-Year Follow-up in a Finnish Population
Fata
l o
r N
on
fata
l M
I (
%)
Prior MI
18.8
3.5
45.0
20.2P<0.001
P<0.001
Prior MINo prior MI No prior MINondiabetic subjects Diabetic subjects
(n=1373) (n=1059)
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Comparison of LDL Cholesterol and Non-HDL Cholesterol Goals
LDL-C Goal(mg/dL)Risk Category
Non-HDL-C Goal (mg/dL)
<100(optional <70)
CHD and CHD Risk Equivalent(10-year risk for CHD >20%)
<130(optional <100)
<130(optional <100)
Multiple (2+) Risk Factors and10-year risk <20%
<160(optional <130)
<1600–1 Risk Factor <190
NCEP ATP III Final Report, Circulation 2002; 106 3143-3421
Major Risk Factors (exclusive of LDL)
•• Cigarette SmokingCigarette Smoking•• Hypertension Hypertension •• HDL < 40 mg/HDL < 40 mg/dLdL•• Family history of premature CHD Family history of premature CHD
NCEP ATP III Final Report, Circulation 2002; 106 3143-3421
LDL-C levels of all adults (United States)
More than 3 in 4 American adults have LDL-C levels of 100 mg/dLor higher
•• Dyslipidemia is a leading risk factor for CHDDyslipidemia is a leading risk factor for CHD——the most the most prevalent form of CVDprevalent form of CVD
Unpublished data from the Third National Health and Nutrition Examination Survey (NHANES III), CDC 1994; data from 1991-1994. Summary report, March 2000.Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III). JAMA. 2001;285:2486-2497.
29%Near or above optimal
(100-129 mg/dL)
24%Optimal
(<100 mg/dL)
6%Very high
(≥190 mg/dL)
13%High
(160-189 mg/dL)
28%Borderline high
(130-159 mg/dL)
76%≥100 mg/dL
18
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Pygmy Pygmy ≈≈100100
San San ≈≈ 120120
HazdaHazda ≈≈110110
50 70 90 110 130 150
San
Pygmy
Ikung
Inuit
HazdaHunter-Gatherer Humans
Mean Total Cholesterol (mg/Mean Total Cholesterol (mg/dLdL))
La Rosa JC et al. JAMA 1999;282:2340-2346. | Crouse JR III et al. Arch Intern Med 1997;157:1305-1310. | Pedersen TR et al. Am J Cardiol 1998;81:333-335.
Reprinted from Illingworth DR. Med Clin North Am. 2000;84:23–42, with permission from Elsevier
Limited.
Pharmacologic Therapy:Pharmacologic Therapy:Dose Response of Different Dose Response of Different StatinsStatins
LDL-C = low-density lipoprotein cholesterol
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Jones PH, et al. Am J Cardiol. 2003;92:152–160.
*P < 0.001 vs. atorvastatin 10 mg and simvastatin 20 mg and 40 mg†P = 0.026 vs. atorvastatin 20 mg
-60%
-50%
-40%
-30%
-20%
-10%
0%
Mean
% C
han
ge i
n
LD
L-C
fro
mU
ntr
eate
dB
ase
lin
e
Valu
e
Atorvastatin Rosuvastatin Simvastatin
14% with14% with3 titrations3 titrations
9% with9% with2 titrations2 titrations
18% with18% with3 titrations3 titrations
10 mg 20 mg 30 mg 40 mg
−28
−7−4−7
−46†
−6*−3*
−37
−6−5−3
LDL–C=low-density lipoprotein cholesterol
Pharmacologic Therapy:Pharmacologic Therapy:Dose Response of Different Dose Response of Different StatinsStatins
•• Assess Assess renal functionrenal function before initiating before initiating statinstatin therapytherapy
•• StatinStatin therapy may be used in patients therapy may be used in patients with with chronic kidney diseasechronic kidney disease (some (some statinsstatinsmay need dose adjustments)may need dose adjustments)
•• No need to routinely No need to routinely monitor serum monitor serum creatininecreatinine or or proteinuriaproteinuria
StatinsStatins: : Kidney IssuesKidney Issues
Reprinted from McKenney JM, et al. Am J Cardiol 2006;97:89C–94C, with permission from Elsevier.
30
NKF Recommendations for Statin Dose Adjustment in CKD
Use doses >20 mg/day cautiously in patients with GFR <30
No adjustmentLovastatin
No dose adjustments needed for mild to moderate kidney disease; use caution in patients with severe
kidney disease; fluvastatin not studied at doses >40 mg in these patients
No adjustmentFluvastatin
No adjustmentNo adjustmentNo adjustmentPravastatinStarting dose 5 mg daily in patients with
severe kidney diseaseNo adjustmentSimvastatin
Starting dose 5 mg and NOT to exceed 10 mg in patients with GFR <30No adjustmentRosuvastatin
No adjustment30–90
No adjustment
Adjust for reduced GFR (mL/min/1.73 m2)
No adjustmentAtorvastatin<15<30
National Kidney Foundation. Am J Kidney Dis. 2007;49(suppl 2):S1-S180.
Placebo/Placebo/SimvastatinSimvastatin 20 mg20 mg 2 years2 years ACSACS 22652265 33††
Musculoskeletal AEs Simvastatin 40/80 mg
* Not treatment-related.
14,33814,338
† 9 cases of myopathy.
Muscle Safety: Simvastatin
0.02%0.08%
0.53%
0.0%
0.1%
0.2%
0.3%
0.4%
0.5%
0.6%
20 mg 40 mg 80 mg
% o
f Pat
ient
s w
ith
Myo
path
y/rh
abdo
myo
lysi
s
Vytorin® (simvastatin/ezetimibe) [package insert]. North Wales, PA: MERCK/Schering-Plough Pharmaceuticals; 2006.
•• StatinsStatins are well tolerated by most peopleare well tolerated by most people
•• Some people experience problems with liver function. Some people experience problems with liver function. Elevations in liver Elevations in liver transaminasestransaminases::
–– Occur in 0.5% to 2.0% of Occur in 0.5% to 2.0% of statinstatin users users
–– Are doseAre dose--dependentdependent
–– Are usually reversed with a Are usually reversed with a lowered lowered statinstatin dosedose
–– Usually do not recur with Usually do not recur with rechallengerechallenge or use of another or use of another statinstatin
–– Rarely progress to liver failureRarely progress to liver failure
StatinsStatins: : Liver IssuesLiver Issues
Pasternak RC, et al. J Am Coll Cardiol. 2002;40:567–572.
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•• Initiate Initiate statinsstatins
•• Continue Continue statinsstatins
•• Increase the dose of Increase the dose of statinsstatins
Pasternak RC, et al. J Am Coll Cardiol. 2002;40:567–572. |McKenney JM, et al. Am J Cardiol. 2006;97:89C–94C.
Modest increases* in liver transaminasesare not a contraindication to:
*Increases <3 × the upper limits of normal.
•• Repeat liver function testsRepeat liver function tests–– If values are still high, rule out other causesIf values are still high, rule out other causes
•• Based on clinical judgment, consider:Based on clinical judgment, consider:–– Continuing the Continuing the statinstatin
–– Reducing the dose of the Reducing the dose of the statinstatin
•• Based on a patient population that experienced ALT/AST >3 x ULNBased on a patient population that experienced ALT/AST >3 x ULNon 2 consecutive occasions more than 14 days apart, or other defon 2 consecutive occasions more than 14 days apart, or other defined criteriained criteria
•• Across all doses, 0.5% of Across all doses, 0.5% of atorvastatinatorvastatin patients experienced elevated ALT/ASTpatients experienced elevated ALT/AST
Pasternak RC, et al. J Am Coll Cardiol. 2002;40:567–572. | McKenneyJM, et al. Am J Cardiol. 2006;97:89C–94C.
Lipid Panel
Baseline 6 weeks 3 months Every 6 months
Liver Function Tests
Baseline12 weeks after
starting/increasing therapy
Annually, as needed (when the patient reports
liver symptoms)
Creatine Kinase Test
BaselineAs needed (when patient reports muscle
soreness, tenderness, or pain)
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Bile Acid Bile Acid SequestrantsSequestrants
Bile Acid Sequestrants
•• ColesevelamColesevelam–– Indicated to lower LDL Indicated to lower LDL –– Improve glycemic control in adults w/ Type II Improve glycemic control in adults w/ Type II
•• Maximum dose: 2 Maximum dose: 2 g/dg/d•• MetaMeta--analysis results:analysis results:
−− LDLLDL--C lowering about 9C lowering about 9––13%13%
•• Lowering greater in elderly:Lowering greater in elderly:−− Additive to Additive to statinstatin therapytherapy−− Used in various population groupsUsed in various population groups
•• WellWell--toleratedtolerated
Law M et al. BMJ 2000;320:861-864.Lichtenstein AH et al. Circulation 201;103:1177-1179
Case Study
Patient Profile:Patient Profile: White Female, 44 White Female, 44 y.oy.o..
Occupation:Occupation: Real Estate AgentReal Estate Agent
Social Habits:Social Habits: Never SmokedNever Smoked
rare ETOHrare ETOH
Exercise:Exercise: Runs 20 miles weeklyRuns 20 miles weekly
LRC Follow-up Study: CVD Mortality by Non-HDL-C and LDL-C in Women
LRC = Lipid Research Clinics; RR = Relative risk; CI = confidence interval.
0 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00
RR with 95% CI
Non-HDL-C(mg/dL)
Rate/10,000
<160 17.6
160 to <190 26.5
190 to <220 29.2
≥220 51.3
LDL-C (mg/dL)
<130 25.4
130 to <160 22.8
160 to <190 27.7
≥190 40.1
The Tricks with Trigs
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Triglyceride Reduction
•• Counsel on Diet (Limit or cut out simple Counsel on Diet (Limit or cut out simple carbscarbs/simple sugars on a daily basis)/simple sugars on a daily basis)
•• Start or Increase Exercise 30Start or Increase Exercise 30--45 min of 45 min of aerobic activity 4 x weekaerobic activity 4 x week
•• Omega 3 Fish Oil 2Omega 3 Fish Oil 2--4 grams daily4 grams daily•• Return visit 6Return visit 6--8 weeks8 weeks•• StatinStatin / Fish Oil/ Fish Oil•• NiaspanNiaspan/IR Niacin/IR Niacin•• FibratesFibrates
AHA Recommendations for Omega-3 FA Intake
Kris-Etherton PM et al. Circulation 2002;106:2747-2757.
Population Recommendation
Patients without documented CHD
Eat a variety of (preferably oily) fish at least twice a week. Include oils and foods rich in α-linolenic acid (flaxseed, canola, and soybean oils; flaxseeds; and walnuts)
Patients with documented CHD
Consume ~1 g of EPA+DHA per day, preferably from oily fish. EPA+DHA supplements could be considered in consultation with the physician
Patients needing triglyceride lowering
2–4 grams of EPA+DHA per day provided as capsules under a physician’s care
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Fish Oils and Statins
•• Marine fish oils rich in omegaMarine fish oils rich in omega--3 fatty acids 3 fatty acids ↓↓ triglyceride triglyceride levels & may be effective in combination w/ levels & may be effective in combination w/ statinsstatins to treat to treat pts w/ combined pts w/ combined hyperlipidemiahyperlipidemia
•• Fish oils plus Fish oils plus statinstatin may often be an alternative to may often be an alternative to fibratefibrateplus plus statinstatin
•• Fish oils may have other CV effects complementary to those Fish oils may have other CV effects complementary to those of of statinsstatins, such as:, such as:
–– Reduction in malignant ventricular Reduction in malignant ventricular dysrhythmiasdysrhythmias–– Increased heart rate variabilityIncreased heart rate variability–– Antithrombotic effectsAntithrombotic effects–– Improved endothelial reactivity/relaxationImproved endothelial reactivity/relaxation–– AntiAnti--inflammatory effectsinflammatory effects–– Slight lowering of blood pressureSlight lowering of blood pressure
Bays HE et al. Expert Opin Pharmacother 2003;4:1901-1938.Kris-Etherton PM et al. Circulation 2002;106:2747-2757.
VA-HIT = Veterans Affairs High-Density Lipoprotein Intervention Trial.*p≤0.05. †p = 0.07. ‡Investigator-designated.2531 men with CHD, HDL ≤40 mg/dL, and LDL ≤140 mg/dL were randomized to gemfibrozil (1200 mg/d)or placebo, and followed for a median of 5.1 years.
% C
hang
e(G
emfib
rozi
lvs
Plac
ebo)
Rubins HB et al. N Engl J Med. 1999;341:410-418.
06*
-31*
-22* -22
-29*
-40
-30
-20
-10
0
10
20
LDL-C HDL-C TG Nonfatal CHD Stroke‡
MI or DeathCHD Death
†
Da Col PG et al. Curr Ther Res Clin Exp 1973;53:473-482. | Ellen RL et al. Am J Cardiol 1998;81:60B-65B.
No Dose Limitations(Evaluate Risk-benefit) Avoid Avoid No Dose Limitations
(Evaluate Risk-benefit)No Dose Limitations
(Evaluate Risk-benefit)
Fibrates Dose Limitations (Max 10 mg)
Dose Limitations(Max 10 mg) Avoid No Dose Limitations
(Evaluate Risk-benefit)No Dose Limitations
(Evaluate Risk-benefit)
Niacin >1 G/D No Dose Limitations(Evaluate Risk-benefit)
No Dose Limitations(Evaluate Risk-benefit)
No Dose Limitations(Evaluate Risk-benefit)
No Dose Limitations(Evaluate Risk-benefit)
No Dose Limitations(Evaluate Risk-benefit)
Cyclosporine Dose Limitations (Max 5 mg)
Dose Limitations (Max 10 mg)
Dose Limitations (Max 10/10)
No Dose Limitations(Evaluate Risk-benefit)
No Dose Limitations(Evaluate Risk-benefit)
Amiodarone/Verapamil Not Mentioned Dose Limitations(Max 10 mg)
Dose Limitations(Max 10/10) No Effect Not Mentioned
Warfarin Baseline INR 2–3 ↑ To >4
Baseline INR 1.7–1.8↑ To 2.6–3.4
Baseline INR 1.7–1.8↑ To 2.6-3.4 No Effect No Effect
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HDL Cholesterol
Classification of Serum HDL-C Levels
HDL-C Category
ATP II LevelsATP III Levels
Low HDL-C <35 mg/dL <40 mg/dL
High HDL-C ≥60 mg/dL ≥60 mg/dL
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 1993;269:3015-3023. | Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
AIM HIGHAtherothrombosis Intervention in Metabolic Syndrome w/Low HDL-c/High Triglyceride & Impact on Global Health Outcomes
•• Randomized trial of niacin vs. placebo in the Randomized trial of niacin vs. placebo in the background of background of SimvastatinSimvastatin therapy in ~3,300 people therapy in ~3,300 people w/ CVD, low HDL, and high triglyceridesw/ CVD, low HDL, and high triglycerides
•• Stopped early due to lack of Stopped early due to lack of ““futilityfutility”” w/ about 2/3 of w/ about 2/3 of the events having occurred. the events having occurred. HDLHDL’’ss were higher and were higher and TG levels lower in the niacin group with LDL levels TG levels lower in the niacin group with LDL levels very low and equal in the two groupsvery low and equal in the two groups
•• There were more ischemic strokes in the niacin There were more ischemic strokes in the niacin group.group.
N3-173 Global Risk29/10/2013 15:20:48
Ch
an
ge f
rom
Base
lin
e in
M
ean
Pro
xim
al
% S
ten
osi
s(Δ
%S
)
0
Angiographic Effects of Lipid Drug Classes Meta-Analysis, 12 Trials
755025% Change in LDL% Change in LDL--CC in Rx(%Δ) Placebo-Adjusted
•• Know NCEP ATP III guidelinesKnow NCEP ATP III guidelines
•• Know how to lower LDL through diet and Know how to lower LDL through diet and medicationsmedications
•• Know how to lower nonKnow how to lower non--HDL cholesterol HDL cholesterol adntadnttriglycerides through diet and medicationtriglycerides through diet and medication