Post on 19-Mar-2018
transcript
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Kristine Ziemba, MSN, FNP-BC, CLSAssociate Clinical Director
Cholesterol Management Center, NEHI
September 10, 2017
1. Define Cardiovascular Disease (CVD), global & U.S. statistics
2. Briefly review CVD Risk Factors- causal relationship between abnormal blood cholesterol & CVD
3. Review Cholesterol Treatment Guidelines, Past & Present- generic & brand pharmaceuticals
4. Briefly review RCT data for Statin & non-Statin Therapies
5. Discuss OTC/Herbal supplements for lipid modification
6. Briefly review “Statin Safety” concerns
7. Introduce PCSK9-Inhibitors
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Cardiovascular Disease
Conditions involving:
(a.) Narrowed / blocked blood vessels
* Coronary Heart Disease
* Angina
* Heart Attack
* Stroke
(b.) Heart muscle
* Heart Failure
(c.) Heart Valve Disease
(d.) Heart Rhythm Abnormalities
(e.) Hypertensive Heart Disease
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The Global Burden of Diseases , Injuries & Risk Factors
(2015)
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Currently 92.1 Million Adults living with at least one (1) form of CVD* 2,150 deaths every day* 1 life every 40 seconds
By 2030, it is projected that 43.9 % of the US Adult population will have some form of CVD
Associated with immense HEALTH & ECONOMIC BURDEN in the U.S. and globally
Heart Disease & Stroke Statistics 2017 Update (March 2017)
Age
Gender
Genetics (Family History)
Ethnicity
Tobacco Use
Sedentary Lifestyle
Sleep Apnea
Chronic Kidney Disease
Metabolic Syndrome / Diabetes
Hypertension
Obesity / Overweight
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70-75%
25-30 %
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Centers for Disease Control & Prevention (2015):
73.5 million (31.7%) U.S. Adults have abnormally high LDL (“bad”) cholesterol
Fewer than 1 out of every 3 adults (29.5%) of those people has their LDL under control
Less than ½ (48%) are getting appropriate treatment to lower their LDL
EARLY & AGGRESSIVE
treatment of abnormal blood cholesterol
as one of the
MOST IMPORTANT
means by which to prevent CVD
Karalis, 2004
Published in September 2002*
Based on a “Treat to Target” strategy
Higher Risk Individuals = lower numbers
“The Lower The Better !!!!”
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*Age: years
*Gender: Female Male
*Total Cholesterol: mg/dl
*HDL Cholesterol: mg/dl
*Smoker : No Yes
*Systolic Blood Pressure: mmhg
*Are you currently on
any medications to treat HBP No Yes
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Calculate Your 10-Year Risk
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What’s New and Why ?
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The CV relative risk reduction
associated with
Fixed-Dose,
Maximally Tolerated Statin Therapy
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Healthy dietary patterns
Increased physical activity
Maintain healthy weight
Avoid tobacco / Alternative Nicotine Products
Control BP
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These lifestyle modifications have durably been found to
Lower blood pressure
Lower blood sugar
Lower LDL (Bad Cholesterol)
Raise HDL (Good Cholesterol)
Markedly lower 10-year & life time CV risk
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Rule out Secondary Causes of
Hyperlipidemia
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Estimates 10 year risk of stroke& heart attack in primary prevention (White and African American)
Guides treatment to those most likely to benefit
Highlights large burden of disability from non-fatal events
Also identified high risk groups that likely do not benefit from statin therapy
Stage III/IV HF
CKD on chronic hemodialysis
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For those who do not fall into 1 of the 4 statin benefit groups but have additional risk (ie. Strong family history in a 1st degree relative, Primary LDL-C > 160, Evidence of genetic hyperlipidemia) ~
HS CRP > 2
CAC score > 300 Agtaston Units or > 75th percentile for age, sex, ethnicity
CIMT
< 0.9 ABI
Elevated Lifetime Risk
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Statin Intensity
Moderate Intensity
30 – 49% LDL Reduction*
High Intensity
> 50 % LDL Reduction*
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Based on the TNT, IDEAL, PROVE-IT, SPARCL & CARDS Trials ….
* Fasting lipid panel 4-14 weeks after initiation of therapy
* Monitor every 3-6 months thereafter
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Based on randomized
data reviewed by expert panel …
Moderate intensity: 30 - 49% reduction from baseline untreated LDL
High intensity statins: > 50% reduction from baseline untreated LDL
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• Reinforce continued medication & TLC adherence
&
• Follow up q 3-12 months
Anticipated LDL
Response
• ? Statin Tolerance
• ? Adherence to Therapy
• Exclude Secondary Causes
• Consider adjunctive Rx (*risk)
Less Than Anticipated LDL
Response
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• Coronary Drug Project (CDP)• Niacin (Nicotinic Acid)vs. Placebo
• Secondary prevention trial• Reduction in CVD events in men with
hypercholesterolemia
• Lipid Research Clinics (LRC)• Cholestyramine (Questran) vs. Placebo
• Primary prevention• Reduction in CVD events in men with
hypercholesterolemia
▪ Helsinki Heart Study (HHS)▪ Gemfibrozil (Lopid) vs. Placebo
▪ Primary prevention▪ Reduction in CVD events in men
▪ Veterans Affairs Intervention Trial (VA-HIT)▪ Gemfibrozil (Lopid) vs. Placebo
▪ Secondary prevention▪ Reduction of CVD events in men
▪ Fenofibrate Intervention & Event Lowering in Diabetes (FIELD)▪ Fenofibrate (Tricor) vs. Placebo
▪ Primary prevention▪ Reduction of CVD events in diabetics▪ No secondary prevention benefits
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Focus on residual CV risk
beyond LDL
Back to pre-specified lipid targets
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*No recommendation for or againstLDL / Non-HDL Targets
*Lack of RCT evidence to support titration of pharmacologic therapy once LDL goal achieved - citing no further reduction in ASCVD events
Ensuring aggressive therapy aimed at lowering atherogeniccholesterol & CVE risk
Facilitating effective communication b/w pt’s and providers to
maximize long-term adherence to treatment
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Lower Is Better
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Primary Prevention Trials
Secondary Prevention Trials
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*Appropriate Statin-Intensity- 4 Statin Benefit Groups
*Routine use of Non-Statin therapies discouraged
*Max tolerated Statin as 1st line Rx for LDL & Non-HDL
*Adjunctive Rx with Non-Statintherapies (CAI, BAS, FAD, NA) may be considered if LDL & Non-HDL not
at goal
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May 2017
*Differs from ACC/AHA Guidelines:
Endorses 2002 NCEP ATP III “treating to targets”
* Similar to ACC/AHA Guidelines:
Endorses* MNT (low chol, Saturated Fat & Trans-Fat, soluble fiber &
plant stanols) * Smoking Cessation* Exercise (aerobic & muscle strengthening)
* Unique from ACC/AHA Guidelines:
Supports use of Apo-B level and LDL-P [ ] for risk stratification & further LDL lowering
Le
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“Treatment goals for dyslipidemia
should be personalized
according to level of CV risk”.
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1. *Statins = 1’ agent to achieve LDL target
2. *Fibrates = used to Rx severe TG > 500 & for CVE reduction only in TG 3. > 200, HDL < 40
* Prescription Om3FA = 2-4 gm/d for Sev TG > 500 (diet supp not FDA approved, use discouraged)
* Niacin = principally as adjunct for TG lowering; not indicated if LDL well controlled on statin
* BAS = may be considered for LDL/Apo B lowering and HDL raising, may increase TG
* Zetia = in c/w statin for additional LDL lowering; monoRx if statin intol
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Cataracts
DiabetesRisk / benefit discussion
Memory impairmentReversible
Muscle symptomsMuscle /Joint Pain (Myalgia/Arthralgia)
Muscle Weakness (Myopathy)
Liver disease Chemical Hepatitis
Fatty Liver Disease / Elevated AST/ALT
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Age > 75 y.o.
Previous intolerance to statin medications
Impaired renal or liver function
Muscle disorders
Concomitant use of drugs affecting statinmetabolism
Poly-pharmacy
Transplant/HIV
Modify intensity
History of hemorrhage stroke
Asian ancestry
2 consecutive LDL levels < 40
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Cholesterol-Lowering Supplements
Plant PhytosterolsoInterfere with absorption of dietary cholo2g/d < LDL 9 to 20%oFelt to reduce CV risk at 800 mg/D
Niacin (“Nicotinic Acid”)oB Vitamino1-3 g / d< LDL up to 30%, raises HDL & < TGoFlushoLiver monitoring
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Cholesterol-LoweringSupplements
RYR ExtractoMain compound, Monacolin K decreases chol production in the liveroPurified form = Lovastatin (Mevacor)oSupplement effect unpredictable
Soluble Fiber oPsyllium (produce, grains) can lower LDL 5-15% + addt’l heart health effects**oBeta Glucan (oats, barley) lowers LDL (3-6 g/d)
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Cholesterol-Lowering Supplements
PolicosanoloDerived from sugar cane, beeswaxoStudied mostly in Cuba, mechanism ???oStudies in Germany/Italy = ineffective
oSE: GI, Rash, adversely interacts with blood thinners
oNot recommended
GarlicoInconsistent results (studies)oSupplements not recommended; if any effect on chol= small
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Cholesterol-LoweringSupplements
Guggul Extract (Guggulipid)oWell studied (U.S./Norway)
* No LDL lowering effecto SE: GI; can interfere w/ Rxo Long-term safety unknown
* Not recommended
Artichoke Leaf ExtractoEvidence suggests only a small effect on cholesterol, further research recommended oNot recommended
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Decrease LDLRDegradation
Increase LDLRReutilization
Triglyceride Rich Lipoprotein Cholesterol (TRL-C)
CTEP-Inhibitors (Directly Raise HDL-C)
Non-HDL Cholesterol as Primary Treatment Target (Replacing LDL-C ?????)
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The “2013 ACC/AHA Guideline on The Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults” considers which of the following Statin Drug-Dose combinations to be “High-Intensity” Therapy?
A. Atorvastatin (Lipitor) 20 mg Daily
B. Simvastatin (Zocor) 40 mg Daily
C. Rosuvastatin (Crestor) 20 mg Daily
D. Pravastatun (Pravachol) 80 mg Daily
E. Pitavastatin (Livalo) 4 mg Daily
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Which of the Cholesterol Lowering Guidelines discussed DOES NOT endorse the use of “Treatment Targets”?
A. 2013 ACC/AHA Guidelines
B. 2015 NLA Guidelines
C. 2002 NCEP ATP III Guidelines
D. 2017 AACE/ACE Guidelines
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Of the following OTC (Over-The-Counter) supplements,
which IS NOT recommended for cholesterol lowering?
A. OM3 Fatty Acids (Fish Oil)
B. Nicotinic Acid (Niacin)
C. Policosanol
D. Soluble Fiber
E. Plant Phytosterols
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