TARGET VS INTENSITY:UNDERSTANDING THE NEW ACC/AHA LIPID GUIDELINES

Pamela L. Stamm, PharmD, CDE, BCPS, BCACP

Associate Professor, Auburn University Harrison School of Pharmacy

October 26, 2014

DISCLOSURES

I have NOTHING to disclose

Where do you provide care?

Community / specialty pharmacy

Long term care pharmacy

Hospital

Academia

I am retired!!!!!!!

D

B

A

C

E

Who performs?

Lipid screenings

Lifestyle counseling / programs

Adjusts in medications

Monitoring / Lab ordering

B

A

C

D

Objectives

• Compare and contrast the 2013 ACC / AHA Guidelines for the Treatment of Blood Cholesterol to previous guidelines

• Compare and contrast the new Pooled Estimates Cardiovascular Risk Calculator to other risk calculators

• Initiate, reassess, and monitor LDL lowering therapy in adults and elderly patients

• Communicate the updated ACC/AHA cholesterol guidelines to patients and prescribers

Previous Guideline Approach

• LDL targets based on estimated absolute risk• Treat to Target Approach• Lower [LDL] is better

3 Main Publications

http://my.americanheart.org/professional/ScienceNews/Clinical-Practice-Guidelines-for-Prevention_UCM_457211_Article.jsp

Lifestyle Guideline

s

Blood Cholester

ol

Risk Assessme

nt

Lifestyle Guidelines

• Applies to adults < 80 yoa

• Most trials reviewed• Included patients with CVD risk factors• Excluded trials with significant weight loss• Excluded people on antihypertensive and lipid lowering therapies

2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk

Circulation. 2013 doi:10.1161/01.cir.0000437740.48606.d1.

Lifestyle Guidelines

Addressed 3 key questions:

1. What is the impact of physical activity on BP and lipids?

2. What is the impact of dietary patterns / micronutrient composition on CVD risk factors?

3. What is the impact of sodium and potassium on CVD risk factors and outcomes?

Circulation. 2013 doi:10.1161/01.cir.0000437740.48606.d1.

Which Diet?

Mediterranean Diet

South Beach DietZone Diet

Adkins Diet

Step 1 and 2 Diets

Isocaloric Diets

Portfolio Diet

Meal Replacement Diets

Opitmal Macronutrient Intake Strategies Diet

Advice on Dietary Patterns

Take Home Points on Diet

• It’s the overall pattern that matters most• Reduce calories from saturated fat

• Aim for 5-6 % of calories of saturated fat • Lowers LDL ~ 11%

• Reduce calories from trans fat• Reduce sodium by 1,000 mg per day • It is unclear if reducing dietary cholesterol reduces LDL-C

Circulation. 2013 doi:10.1161/01.cir.0000437740.48606.d1.

How Much Exercise & What Kind?

• 120-160 min of moderate-intensity / wk, or

• 75 minutes of vigorous-intensity aerobic physical activity a week ,

or • equivalent combination of the above

• Aerobic activity • Last at least 10 minutes• Spread throughout the week

3 Main Publications

http://my.americanheart.org/professional/ScienceNews/Clinical-Practice-Guidelines-for-Prevention_UCM_457211_Article.jsp

Lifestyle Guideline

s

Risk Assessme

ntBlood

Cholesterol

ATP• Emphasis: LDL reduction /

goals

• Comprehensive approach to care

• Primarily expert opinion

• Stressed CHD prevention

ACC/AHA 2013

• Emphasis: fixed dose statin

• Limited to 4 specific questions

• Limited expert opinion

• Stresses ASCVD prevention

Emphasis on Statin Therapy and

Key Findings from RCTs and Meta-analyses

Definitions

Primary Prevention: • No previous ASCVD event • Includes those with subclinical

atherosclerosis

Secondary Prevention: • Previous ASCVD

Definitions

Clinical ASCVD: atherosclerotic cardiovascular disease• CHD (coronary heart disease)• Stroke• PAD (peripheral artery disease)

Hard ASCVD• Nonfatal MI• Coronary Heart Disease (CHD) Death• Stroke (Fatal or nonfatal)

0.4 0.8 1.2

Nonfatal MICHD deathAny major coronary event CABGPTCAUnspecifiedAny coronary revascularisationIschaemic strokeHaemorrhagic strokeUnknown strokeAny strokeAny major vascular event

0.74 (0.69 - 0.78)0.80 (0.73 - 0.86)0.76 (0.73 - 0.79)0.76 (0.69 - 0.83)0.78 (0.69 - 0.89)0.76 (0.70 - 0.83)0.76 (0.73 - 0.80)0.80 (0.73 - 0.88)1.10 (0.86 - 1.42)0.88 (0.76 - 1.02)0.85 (0.80 - 0.90)

0.79 (0.77 - 0.81)

Reduction in risk is proportional for each 39mg/dL decrease in LDL-C

Lancet 2010; 376: 1670–81

20

Relative risk (CI) per39mg/dL LDL-C

reduction

Statin better Control better99% or 95% CI

Reduction in MAJOR VASCULAR EVENTS is proportional for each 39 mg/dL decrease in LDL-C Lancet 2010; 376: 1670–81

0.5 0.75 1 1.25 1.5

Relative risk (CI) per39 mg/dL LDL-C decr.

Statin/more betterControl/less better

More vs. less intense statin

A to Z PROVE-IT

TNT IDEAL SEARCH

257 (7.2)406 (11.3)

889 (4.0)938 (5.2)

1347 (3.6)

282 (8.1)458 (13.1)

1164 (5.4)1106 (6.3)1406 (3.8)

Total 3837 (4.5) 4416 (5.3) 0.72 (0.66 - 0.78)

No. of events (% pa)

Statin/moreControl/less

99% or 95% CI

0.75 1.25Statin better Control better

Reduction in MAJOR VASCULAR EVENTS is proportional per 39mg/dL LDL-C reduction, by baseline LDL-C Lancet 2010; 376: 1670–81

< 78

> 78, < 97.5

> 97.5, < 117

> 117, < 136.5

> 136.5

0.87 (0.60 - 1.28)

0.77 (0.62 - 0.97)

0.76 (0.67 - 0.86)

0.77 (0.71 - 0.84)

0.80 (0.77 - 0.84)

Baseline LDL (mg/dL) in Statin vs control

Relative risk (CI) permmol/L LDL-C reduction

Old Basic Approach

Assess hard CHD Risk

Select Statin

Titrate Statin to LDL Goal

Assess hard ASCVD Risk

Select Moderate / High Intensity Statin

Confirm LDL Response

New Basic Approach

Recognizing need for Medications

Four defined “Statin Benefit Groups”

1. Persons with clinical ASCVD

2. Baseline LDL-C > 190mg/dL

3. Persons with DM & LDL-C 70-189mg/dL

4. 10 year hard ASCVD risk > 7.5%

Diabetes (40-75

yrs)

Clinical ASCVD

LDL-C > 190

mg/dL

Estimate ASCVD Risk

< 75 yrs

High Intensity

< 75 yrs

Risk > 7.5%Risk < 7.5 % or > 75 yrs

ModerateIntensity

> 75 yrs

> 75 yrs

Age > 21 years

Estimate ASCVD Risk40-79 years

5 - 7.5%Moderate

Intensity Statin or consider

other risk factors

> 7.5%Moderate or

High Intensity Statin

When Risk is Uncertain (<7.5%)

Measure Supports Initiating Therapy

Family history of premature CHD

Male <55 yoa

Female <65 yoa*

hs-CRP > 2.0 mg/L

CAC score > 300 Agatston units or >/=75 percentile for age, sex, and ethnicityⱡ

ABI <0.9

*1st degree relative; ⱡ see http://www.mesa-nhlbi.org/CACReference.aspx for additional information,

Defining Statin IntensityHigh-Intensity

(mg)Moderate-Intensity

(mg)Low-Intensity

(mg)↓ LDL–C about

≥50%↓ LDL–C about

30% to <50%↓ LDL–C

< 30%

Atorva (40†)–80 Rosuva 20 (40)

Atorva 10 (20) Rosuva (5) 10 Simva 20–40‡Prava 40 (80) Lova 40 Fluva XL 80 Fluva 40 bidPitava 2–4

Simva 10Prava 10–20Lova 20Fluva 20–40Pitava 1

True -or- False?

If a patient with ASCVD experiences a >50% decrease in LDL-C on

treatment with a Moderate Intensity Statin, the dose does NOT need to be increased to that of a High Intensity

Statin.False

A 65 yo patient calls to refill his Simvastatin 80mg. He has a

history of ASCVD. What do you do?

Refill it, it is a high intensity statin

Refill it if he has been on it > 12

months

Reduce dose to 40mg/day for

safety

Change it to 80mg of Atorvastatin

D

B

A

C

Paired Exercise:

Educate Provider on this Intervention

Recommend switching simvastatin 80mg to high

intensity statin

When is A Moderate Intensity Preferred for

Safety?

• Multiple comorbidities (renal / hepatic dysfunction)• Unexplained ALT > 3 ULN• Previous statin intolerance• Drug interactions• Age > 75 yrs• Asian ancestry (rosuvastatin)• H/o hemorrhagic stroke

Special Populations

• Those under 40 yrs

• Elderly (75 yrs or older)

• HF

• Hemodialysis

• Diabetes with HF or Hemodialysis

So what about LDL and NonHDL Targets?

• “No recommendation for or against”

• For those who want an objective target – look at LDL response

• Moderate intensity ↓ 30-50%• High intensity ↓ 30-50%• But it is not a substitute for intensity!!!

• Other guidelines still contain goals (ADA, AACE, IAS, NLA)

So when should we combine therapy?

• When Triglycerides > 500mg/dL

• Inadequate LDL response for• ASCVD < 75 yrs• Baseline LDL > 190 mg/dL• DM, 40-75 yrs

JD has ASCVD risk > 7.5%. He takes niacin SA 2g daily, rosuvastatin 40mg, &

fenofibrate 160mg. His LDL 54, TG 96.

Does he meet criteria for combination therapy?

JD has ASCVD risk > 7.5%. He takes niacin SA 2g daily, rosuvastatin 40mg, &

fenofibrate 160mg. His LDL 54, TG 96 What changes do you make?

Stop the niacin

Stop the niacin and the fenofibrate

Reduce rosuvastatin to 10mg/day

Change to pravastatin for safety

Nothing

D

B

A

C

E

The Lancet 2011; 377:2181-2192 (DOI:10.1016/S0140-6736(11)60739-3)

SHARP Trial

TK has statin intolerance. ASCVD risk > 7.5%. Her baseline LDL 130, TG 150, HDL

35. What do you start?

Cholestyramine or other BAS

Niacin

Ezetimibe

Gemfibrozil

Fenofibrate

D

B

A

C

E

Evidence summary p 134-135 Full

Report on Blood

Cholesterol

Safety Monitoring

Baseline• ALT • CK (only if at perceived risk of adverse muscle

events)

Follow-up• ALT if symptoms suggest hepatotoxicity• CK with muscle weakness, pain, cramping, stiffness,

generalized fatigue

Efficacy Monitoring

• Lipids 4-6 weeks after initiation and dose change to assess LDL-C response

• 6-12 months thereafter

• More frequently if needed for adherence

Points to Note

• No recommendation FOR or AGAINST specific LDL or NonHDL targets

• Decrease dose if intolerance occurs - even low intensity statins reduce ASCVD events

• May decrease dose if LDL-C < 40mg/dL on 2 occasions

• Insufficient evidence to treat baseline LDL-c < 70 mg/dL

3 Main Publications

http://my.americanheart.org/professional/ScienceNews/Clinical-Practice-Guidelines-for-Prevention_UCM_457211_Article.jsp

Lifestyle Guideline

s

Blood Cholester

ol

Risk Assessme

nt

Why not Framingham or other existing tools?

• Historically dated populations

• Limited ethnic diversity

• Narrowly defined endpoints, lacked stroke

• Endpoints influenced by cohort providers (elective procedures)

• Endpoints with poor diagnostic reliability (HF & angina)

Pooled Risk Calculator

• Developed from 5 major cohorts• Validated on 2 external cohorts

• Designed for primary prevention patients NOT on drug therapy

• Provides 2 different risk assessments• 10 year risk of hard ASCVD• Lifetime risk for someone age 50 yrs

Pooled Risk Calculator

• Downloadable excel spreadsheet: my.americanheart.org/cvriskcalculator

• Online calculator: see above

• ASCVD Estimator App (Android & iPhone)

Who qualifies for risk assessment

• C or AA (possibly others)

• Males and Females

• Aged 40-79

• No known ASCVD

• NOT on lipid altering therapy

For which of the following patients can ASCVD risk be performed?

35 yo C Male

55 yo M with diabetes

65 yo Asian female

78 yo CM with h/o strokeD

B

A

C

Independent Risk Factors

Framingham OmnibusAge √ √

Tobacco Use √ √

Diabetes √

HTN treatment

√ √

TC √ √

HDL √ √

SBP √ √

Other potential Risk Factors

• Those that did not have sufficient evidence to support use at this time

• CKD• Albuminuria• Cardiorespiratory fitness• ApoB

• Those to NOT use• CIMT

Explain to a given patient their ASCVD Risk

• 55 yr old Non-Hispanic Caucasian Female• Denies tobacco and DM• Diagnosed with HTN

• 154/92 on Lisinopril 40mg daily• TC 240, LDL 170, HDL 60

1. Determine her ASCVD risk?2. Explain her risk to her (neighbor)?

For every 100 persons like you, 4 – 5 will experience a NF MI, Heart related death, or stroke.

95-96 will not.

True -or- False?

I can estimate someone’s longer term risk by multiplying the 10

year risk by X.False

Lifetime Risk Calculator

• Estimate for a person 50 yoa

• Not a continuous function

• Fit into 1 of 5 risk categories for gender

Lloyd-Jones et al. Circulation 2006;113(6)791-8.

Cumulative incidence of CVD adjusted for the competing risk of death for men & women according

to aggregate risk factor burden at 50 yrs.

Lloyd-Jones D et al. Circulation 2006;113:791-798 Copyright © American Heart Association, Inc. All rights reserved.

Notable patterns for risk > 7.5%

Age ofNon Smoker

Age of Smoker

AA Male 66 53

C Male 63 57

AA Female 70 63

C Female 71 66

Controversies / Myths

“New risk assessment tool overestimates risk”

“More people will take statins!”

78 yo M requests a refill of atorvastatin 80mg daily.

PMH: h/o CVA, HTN, and OACurrent Meds: Atorvastatin, ASA, Lisinopril,

Acetaminophen

Denies any symptoms of muscle pain, weakness, cramping

78 yo M requests a refill of atorvastatin 80mg daily.

Refill it

Suggest he stop therapy

Reduce dose to 40mg/day

Reduce dose to 20mg/dayD

B

A

C

Summary

• New guidelines are designed to • Better identify those needing treatment• Simplify treatment options• Minimize Clinical Inertia

• Many questions remain unanswered• They conflict with other recent guidelines