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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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