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2013 ACC/AHA Guidelines on the

Treatment of Blood Cholesterol to

Reduce Atherosclerotic Cardiovascular

Risk in Adults2014 AAHP Fall Seminar

Sherry Myatt, PharmD, BCPS

Assistant Director of Pharmacy for Clinical Services

UAMS Med Center

Disclosures

• I have no relevant financial interests to disclose for this

talk

Overview

• NHLBI vs ACC/AHA

• First new guidelines since ATP III guideline update in 2004

• Review the most important statements or changes presented in these guidelines

• No longer have therapeutic targets

• New risk calculator

• Use medications proven to reduce risk, ie statins

• Avoid medications or supplements that may lower the cholesterol number, but have no data to decrease CV risk

• Not a comprehensive approach to lipid management

• Finally, review questions and controversies that have arisen since publication.

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Objectives for Pharmacists

1. Outline the main differences between the 2013 ACC /AHA cholesterol management guideline and the previous NCEP guideline. Discuss the controversy about the new guideline.

2. Describe the 4 statin benefit groups identified in the 2013 guideline and identify which patients to target for lipid lowering therapy

3. Describe the recommended intensity of statin therapy for each benefit group. List at least 2 regimens of each intensity.

4. Evaluate the recommended initial dose and follow-up of statin therapy.

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Some Patients to Think About…

• 63 yo man with STEMI, discharged on a high intensity

statin

• 26 yo woman with elevated LDL–C of 220 mg/dL, noted

in teens + family history CHD

• 44 yo woman with diabetes, well-controlled hypertension

and micro-albuminuria

• 56 yo African-American woman with multiple ASCVD

risk factors

• 57 yo white man with LDL-C 165 mg/dl

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Don’t Forget Healthy

Lifestyle

• Healthy diet

• Regular exercise

• No tobacco

• Maintain healthy weight

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2013 ACC/AHA/NHLBI Guideline on Lifestyle for

CVD Prevention

• Eat a dietary pattern that is rich in fruit, vegetables, whole grains, fish, low-fat dairy, lean poultry, nuts, legumes, and nontropical vegetable oils consistent with a Mediterranean or DASH-type diet.

• Restrict consumption of saturated fats, trans fats, sweets, sugar-sweetened beverages, and sodium.

• Engage in aerobic physical activity of moderate to vigorous intensity lasting 40 minutes per session three to four times per week

4 Defined Statin Benefit Groups

1. Patients with clinical ASCVD

2. LDL greater than 190 mg/dl

3. Patients with diabetes, age 40-75 years

4. Age 40-75 years that do not meet above

criteria, but have a 10 year risk of >7.5 %

All of these are indicated for statin treatment

1. Patients with Clinical ASCVD

Defined by the inclusion criteria for the secondary prevention statin RCTs:

• Coronary artery disease or peripheral artery disease

• Stroke or TIA*

• Acute coronary syndromes

• Coronary or other arterial revascularization

• PVD presumed to be atherosclerotic

• These patients get High Intensity Statin Therapy

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Identifying ASCVD

This could be identified in several ways:

• Heart catheterization

• Q waves on ECG

• TEE

• Coronary CTA

• Noninvasive testing including, carotid duplex, upper or lower extremity arterial duplex

• Peripheral angiography

2. LDL > 190 mg/dl

• This is one of the few times level of cholesterol

mentioned in the guidelines

• These are patients with familial hyperlipidema

• They deserve special consideration

• Often start with untreated LDL of 325-400 mg/dl

LDL > 190 mg/dl

• These patients get high intensity statin treatment

• If they cannot tolerate high intensity statin therapy, use moderate intensity statin +/- or other agent to achieve >50% reduction of baseline LDL.

• Patients with FH are frequently unable to achieve previous goals even with multiple cholesterol lowering agents

• In this special case, the authors felt that data has shown significant reductions of ASCVD by decreasing LDL > 50%

• Can include statin plus another agent

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3. Diabetics Between 40-75

Years Old

• LDL levels 70-189 mg/dL and no ASCVD

• All have indication for statin

• Level of intensity of statin treatment depends on

calculated 10 year risk

Diabetics Between 40-75

Years Old

• Diabetics with > 7.5% 10 year risk get high intensity

statin therapy

• Diabetics with < 7.5% 10 year risk of CAD get moderate

intensity statin therapy

• Statin indicated in all patients with diabetes

4. Nondiabetic Patients Without

Known CAD with >7.5% 10 year risk

• 10 year and lifetime risk as determined by new Pooled

Cohort Equationss

• Specifically designed for this trial

• Downloadable on AHA or ACC site

• Not without controversy, as the calculator has never

before been published or validated

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CV Risk Calculator

• Sex

• Age

• Race

• Total Cholesterol

• HDL

• Systolic BP

• Treated for HBP

• Diabetes

• Smoker

Risk Factors Used in Calculator

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Data Generated With Calculator

• Patient’s 10 year risk

• 10 year risk of someone the same age with optimized risk

factors

• Patient’s lifetime risk of ASCVD

• Lifetime risk of someone with optimal risk factor levels

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Nondiabetic Patients Without Known

CAD with >7.5% 10 year risk

• Statin indicated in these patients **after a risk to

benefit discussion with their provider

Before initiating statin therapy, clinicians and patients engage in a

discussion of the potential for ASCVD risk reduction benefits,

potential for adverse effects, drug-drug interactions, and patient

preferences

• Moderate to high intensity statin therapy

recommended

What if you don’t fall into one of the 4

categories where statins are indicated?

• There are no recommendations for treatment in selected

individuals who are not in the 4 statin benefit treatment

groups

• In these individuals whose 10 year risk is less that 7.5%,

or when the decision is unclear, other factors should be

considered:

Other Factors to be Considered

• Family history of premature CAD

• LDL > 160 mg/dl

• Increased CRP greater than 2.0

• Coronary calcium greater than 300

• ABI < 0.9

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No Recommendations for These

• No indication for starting or discontinuing statins in the

following:

• Patients < 40 or > 75 years of age with no ASCVD or LDL

> 190

• NYHA class II-IV CHF

• Or those on dialysis

• HIV patients

• Solid organ transplant patients

• Insufficient data from RCT available

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No More Treatment Targets for LDL

or Non-HDL

• This is a huge change for patients and providers.

• No longer treat to target

• Doesn’t fit in well with “know your numbers.”

• Goal is no longer “lower is better.”

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New Perspective

on LDL–C & Non-HDL–C Goals

• Lack of RCT evidence to support titration of drug therapy

to specific LDL–C and/or non-HDL–C goals

• Strong evidence that appropriate intensity of statin

therapy should be used to reduce ASCVD risk in those

most likely to benefit

• Quantitative comparison of statin benefits with statin risk

• Nonstatin therapies – did not provide ASCVD risk

reduction benefits or safety profiles comparable to statin

therapy

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Why Not Continue to Treat to

Target?

Major difficulties:

1. Current RCT data do not indicate what the

target should be

2. Unknown magnitude of additional ASCVD risk

reduction with one target compared to another

3. Unknown rate of additional adverse effects

from multidrug therapy used to achieve a

specific goal

4. Therefore, unknown net benefit from treat-to-target

approach

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Non-Statin Therapies

• For hyperlipidemia, non statin therapies, alone or in combination with statins, do not provide acceptable risk reduction benefits compared to adverse effects.

• These include:

• Zetia

• Fibrates

• Fish oil

• Niacin

• For the most part, these should be avoided with few exceptions

• Why don’t non-statins play a more prominent role in the new guidelines?

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Recent Troublesome Non-Statin

Trials

• Fibrate

• ACCORD. N Engl J Med 2010; 362:1563-1574

• FIELD. Lancet; 366:1849-1861

• Fish oil

• Risk and Prevention Study Group. N Eng J Med 2013; 368:1800-1808

• Omega-3 Fatty Acid Supplementation and Risk of Cardiovascular Events. JAMA 2012; 308(10):1024-1033

• SELECT. JNCI 2013; July 10

Recent Troublesome Non-Statin

Trials

• Niacin

• HPS2-THRIVE (Treatment of HDL to reduce the Incidence of Vascular Events.) European Heart Journal 2013; 34:1279-1291

• AIM-HIGH N Eng J Med 2011; 365:2255-2267

• Zetia

• ENHANCE. N Eng J Med 2008; 358:1431-1443

• ARBITER 6-HALTS. N Eng J Med 2009; 361:2113-2122

• SEAS. N Eng J Med; 359:1343-1356

• IMPROVE-IT ongoing

Non-Statin Therapy

Considerations

• Use the maximum tolerated intensity of statin

• Consider addition of a nonstatin cholesterol-lowering drug(s)

• If a less-than-anticipated therapeutic response persists

• Only if ASCVD risk-reduction benefits outweigh the

potential for adverse effects in higher-risk persons:

• Clinical ASCVD <75 years of age

• Baseline LDL-C ≥190 mg/dL

• Diabetes mellitus 40 to 75 years of age

• Nonstatin cholesterol-lowering drugs shown to reduce

ASCVD events in RCTs are preferred

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What if your patient cannot tolerate

statin due to muscle weakness?

• Readdress lifestyle issues

• Decrease the dose of statin

• Try another statin

• Check vitamin D levels and replace

• Evaluate for other conditions that may

cause muscle weakness

What if your patient cannot tolerate

statin due to muscle weakness?

• If unexplained severe muscle symptoms or

fatigue develop during statin therapy:

• Promptly discontinue the statin

• Address possibility of rhabdomyolysis with:

• CK

• Creatinine

• urine analysis for myoglobinuria

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4 Defined Statin Benefit

Groups

• CAD, CVD or PAD

• LDL >190 mg/dl

• Diabetics, age 40-75 years with LDL 70-189 mg/dl

• Age 40-75 years that don’t meet above criteria, but have a

calculated 10 year risk of > 7.5% of developing CAD

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No Longer Appropriate Strategies

• Treat to target

• Lower is better

• Treat for lifetime risk

Questions Remain

• Add in data for groups where RCT become more available

• Treatment of hypertriglyceremia

• Use of non-HDL in decision making

• Whether on-treatment markers such as Apo B, Lp(a), or LDL particles are useful to guide treament

• Best approaches to using noninvasive imaging for refining risk estimates

Likely Future Updates

• How lifetime risk should be used and the optimal age to begin statin therapy to reduce lifetime risk of ASCVD

• Subgroups of individuals with heart failure or undergoing dialysis that might benefit from statin therapy

• Long-term effects of statin-associated new onset diabetes and management

• Efficacy and safety of statins in patients excluded from RCT to date (eg, HIV positive or solid organ transplant)

• Role of pharmacogenetic testing

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Controversies

• Calculator may overestimate risk and lead to inappropriate use of statins, specifically in primary prevention.

• During the review phase of the guidelines, Dr. Ridker and Cook pointed out that the calculator was not working among the populations it was tested on by the guideline authors.

• Concern that the calculator over predicted risk by 75 –150%

• So patients from a previously studied population might have had an actual risk of 4% but the calculator might have calculated a risk of 8%, warranting statin therapy.

Calculations may not always make

sense

• Dr. Nissen cites examples

• 47 year old African-American with TChol 160, HDL 44, SBP 130 on 25 mg HCTZ, nondiabetic, nonsmoker has 10 year risk of 7.6%

• 60 year old African-American with no risk factors, TChol 150, SBP 125 on no meds, nondiabetic, nonsmoker has 10 year risk of 7.5%

• Similar for a healthy white man aged 58

• 44 year old nonsmoking, nondiabetic white man with strong family history of MI, total cholesterol of 250 mg/dl, LDL 182, HDL 28, SBP 120 on no meds has 5% calculated risk.

Where do we go from

here?

• Suspend guidelines?

• Evaluate risk calculator accuracy using current

populations and make adjustments.

• Continue guideline and review new evidence as it

becomes available

• Continue the discussion

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Remember Our Patients?

1. 63 yo man with STEMI, discharged on a high intensity

statin

2. 26 yo woman with elevated LDL–C of 220 mg/dL,

noted in teens + family history CHD

3. 44 yo woman with diabetes, well-controlled

hypertension and micro-albuminuria

4. 56 yo African-American woman with multiple ASCVD

risk factors

5. 57 yo white man with LDL-C 165 mg/dl

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Remember Our Patients?

ASCVD risk calculation NOT needed:

• Case 1: ASCVD

• High-intensity statin therapy for optimal risk reduction in those <75 years who tolerate it

• Moderate intensity may be initiated or continued if >75 yo or if high-intensity Rx not safe or not tolerated

• Case 2: LDL–C ≥190 mg/dL (secondary causes ruled out)

• Evidence supports high-intensity statin therapy

• LDL–C levels may still remain very high, even after the intensity of statin therapy has been achieved; addition of a nonstatin drug may be considered to further lower LDL–C

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Remember Our Patients?

ASCVD risk calculator useful:

• Case 3: Diabetes; 40-75 yo; LDL–C 70-189 mg/dL• Moderate-intensity statin to be initiated or continued

• High-intensity statin reasonable if estimated 10-year ASCVD risk calculated to be >7.5%

• Cases 4 & 5: Primary prevention; 40-75 yo; LDL–C 70-189 mg/dL• Use Pooled Cohort Equations (risk calculator) to estimate 10-year ASCVD

risk for African American and white individuals to guide initiation of statin therapy

• Clinician-patient discussion before treatment is initiated

• Moderate or high intensity statin when >7.5% 10-year ASCVD risk

• Moderate intensity statin therapy reasonable when >5% 10-year ASCVD risk or when other characteristics that increase ASCVD risk are present

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Summary

• No longer use targets for cholesterol levels

• Identify patients at risk

• Know the 4 high risk groups

• Use medications proven to reduce risk, ie statins

• Encourage healthy lifestyle

• Understand that questions and concerns remain

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“Now this is not the end. It is not even the

beginning of the end. But it is, perhaps, the

end of the beginning”

Winston Churchill, 1942

Quiz

• Which of the following is not one of the risk factors considered in the10year CV risk calculator?1. Smoking

2. Gender

3. Age

4. CAD

• Which of the following statins would be considered “high intensity”?1. Lovastatin 80mg/d

2. Atorvastatin 80mg/d

3. Rosuvastatin 10mg/d

4. Simvastatin 40mg/d

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Quiz

• Which recommendation is found in the new guidelines?

1. An LDL goal of < 100 mg/dL is recommended for patients with CV disease.

2. Patients aged 40-75 with DM should get a statin.

3. Most pts over age 75 should get a high intensity statin.

4. Niacin should be started if HDL is < 40 mg/dL.

• Which patient requires a risk assessment using the Pooled Cohort Analysis?

1. A 30 year old white male with LDL-c 205

2. A 70 year old woman with a recent CVA

3. A 50 year old black man with HTN

4. A 45 white woman with DM and PVD

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