copyright © 2013, canadian cardiovascular society 06/10/2015 1 anderson tj, gregoire j et al., can...

Copyright © 2013, Canadian Cardiovascular Society23-04-19 1

Anderson TJ, Gregoire J et al., Can J Cardiol 2013 Feb;29(2): 151-167

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http://www.onlinecjc.com/



Canadian Cardiovascular Society Guidelines

2012 UPDATE Diagnosis and Treatment of Dyslipidemia

for the Prevention of Cardiovascular Disease in the Adult



Revision/Correction History

Date Revision

April 25, 2013 Adjusted ranges in slide 24 and 27 to be inclusive (IE ≥, ≤) to match publication

2012 CCS Dyslipidemia Guidelines Update



Primary PanelTodd J Anderson MD, Libin Cardiovascular Institute of Alberta, University of Calgary, AlbertaJean Grégoire MD, Institut de Cardiologie de Montréal, Université de Montréal, QuébecRobert A. Hegele MD, Robarts Research Institute, London, Ontario Patrick Couture MD, Centre Hospitalier Universitaire de Québec, Québec City, Québec G. B. John Mancini MD, University of British Columbia, Vancouver, British Columbia Ruth McPherson MD, PhD, University of Ottawa Heart Institute, Ottawa, Ontario Gordon A. Francis MD, St Paul’s Hospital, University of British Columbia, Vancouver, British Columbia Paul Poirier MD, PhD, Institut Universitaire de cardiologie et de Pneumologie de Québec, Quebec City, Québec David C. Lau MD, PhD, Libin Cardiovascular Institute of Alberta, University of Calgary, Alberta Steven Grover MD, McGill University Health Center, Montreal, Quebec Jacques Genest Jr., MD, McGill University Health Center, Montreal, Quebec André C. Carpentier MD, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec Robert Dufour MD, Institut de Recherches Cliniques de Montréal, Montréal, Québec Milan Gupta MD, Department of Medicine, McMaster University, Hamilton, Ontario Richard Ward MD, University of Calgary, Alberta Lawrence A. Leiter MD, St Michael’s Hospital, University of Toronto, Ontario Eva Lonn MD, Population Health Research Institute, McMaster University, Hamilton, Ontario Dominic S. Ng MD, PhD, St Michael’s Hospital, University of Toronto, Ontario Glen J. Pearson Pharm D, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta Gillian M. Yates MN, NP, QE II Health Sciences Centre, Halifax, Nova Scotia James A. Stone MD, PhD, Libin Cardiovascular Institute of Alberta, University of Calgary, Alberta Ehud Ur MB, University of British Columbia, Vancouver, British Columbia




IntroductionTodd J Anderson, MD

Who to screen & risk assessmentRobert Dufour, MD

Levels of RiskMilan Gupta, MD

Secondary testing Todd Anderson, MD

Health BehavioursGillian M. Yates, MN NP

Statin intolerance Glen J. Pearson, Pharm D

CasesJean Grégoire MD

Open questions




Changes since 2009

• GRADE recommendations• Addition of CKD definitions and treatment• Lower age for treatment in diabetes – CDA harmonization• Addition of non-HDL –C as alternative target• Recommendation for secondary testing in selected patients• More explicit recommendations for health behaviour

changes• Statin intolerance approach • Cardiovascular Age determination






Who to Screen & Risk AssessmentRobert Dufour, MD



Risk assessment1. We recommend that a cardiovascular risk assessment using the “10 Year Risk”

provided by the Framingham model be completed every 3 to 5 years for men age 40 to 75, and women age 50 to 75. This should be modified (percent risk doubled) when family history of premature CVD is positive (i.e. 10 relative <55 years for men; <65 years for women). A risk assessment may also be completed whenever a patient’s expected risk status changes. Younger individuals with >1 risk factor for premature CVD may also benefit from a risk assessment to motivate them to improve their lifestyle. (Strong Recommendation, Moderate-quality Evidence)





Risk assessment and Framingham Model




CVD − Cardiovascular risk for menPOINTS RISK POINTS RISK POINTS RISK

-3 or less < 1 % 5 3.9 % 13 15.6 %

-2 1.1 % 6 4.7 % 14 18.4 %

-1 1.4 % 7 5.6 % 15 21.6 %

0 1.6 % 8 6.7 % 16 25.3 %

1 1.9 % 9 7.9 % 17 29.4 %

2 2.3 % 10 9.4 % 18+ > 30 %

3 2.8 % 11 11.2 %

4 3.3 % 12 13.3 %

Multiplied by 2 when family history of premature CVD is positive



Limitations of 10 year risk estimates

• Sensitive to the patient’s age• Majority of individuals identified as being at low risk• More accurate among younger individuals• Competing risk increases with age (i.e cancer)• Risk categories (low, inter.,high) chosen arbitrary by consensus• Sub-optimal understanding and use

Despite the limitations assessing total CVD risk improves management of blood pressure and blood lipids




Anderson TJ, Gregoire J et al., Can J Cardiol 2013 Feb;29(2): 151-167Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA. 2002;288(4):462-467

Adherence to Statins is Sub-Optimal Among Canadians



Risk Assessment: Recommendation 2

1. We recommend calculating and discussing a patient’s “Cardiovascular Age” to improve the likelihood that patients will reach lipid targets and that poorly controlled hypertension will be treated

(Strong Recommendation, High-Quality Evidence).




Risk Assessment: Values & preferences• The primary evaluation of risk is the modified 10-year

Framingham Risk Score (FRS)

• Given the overlap in risk factors for diabetes, a simultaneous evaluation of cardiometabolic risk for diabetes may be useful to motivate lifestyle changes

• It is well known that a 10-year risk does not fully account for risk in younger individuals

• In these individuals, the calculation of a Cardiovascular Age has been shown to motivate subjects to achieve risk factor targets




Risk Assessment: Practical TipFor patients older than 75 years of age, the Framingham model is not well validated. Though clinical studies are currently under way to address this group, at this point clinical judgement is required in consultation with the patient to determine the value of pharmacotherapy.

One approach is extrapolation of the modified FRS, and this approach identifies most subjects as having intermediate- to high-risk based on age.





Cardiovascular Age Tables / Diabetes: NO




Cardiovascular Age Tables / Diabetes: YES




Cardiovascular Age Tables / Diabetes: NO




Cardiovascular Age Tables / Diabetes: YES





Levels of RiskMilan Gupta, MD



Low risk recommendations

1. Pharmacotherapy with LDL-C ≥ 5.0 mmol/L, or evidence of genetic dyslipidemia (e.g. familial hypercholesterolemia) (Strong Recommendation, Moderate-Quality Evidence).

2. ≥ 50 % reduction of LDL-C after treatment is initiated (Strong Recommendation, Moderate-Quality Evidence)




Low risk recommendations

Values and preferences: Unchanged. Less clinical trial evidence, so practice will vary and depend on patient wishes and clinical evaluation.

For subjects with 5-9% risk: - more frequent monitoring of risk- discuss risks/benefits of statin therapy- judicious use of secondary testing.




Intermediate Risk Recommendations1. IR category: adjusted FRS > 10% and <20%

(Strong Recommendation, Moderate-Quality Evidence)

2. Treat IR individuals with LDL-C > 3.5 mmol/L (Strong Recommendation, Moderate-Quality Evidence)

3. In IR individuals with LDL-C < 3.5 mmol/L, apo B ≥ 1.2 g/L or non-HDL-C ≥ 4.3 mmol/L can help identify patients to benefit from pharmacotherapy (Strong Recommendation, Moderate-Quality Evidence)

4. Target LDL-C ≤ 2.0 mmol/L or ≥ 50% reduction once treatment is initiated (Strong Recommendation, Moderate-Quality Evidence).

Alternative targets: apo B ≤ 0.8 g/L or non-HDL cholesterol ≤ 2.6 mmol/L (Strong Recommendation, Moderate-Quality Evidence).





Non-HDL-C as an alternate target to LDL-C



Intermediate risk and non-HDL: values and preferences• Adding non-HDL-C would seem to contradict the philosophy

of simplifying the guidelines.

• However, apo B is not available in some jurisdictions, while non-HDL-C is available without any additional cost or testing.

• Also, increasing data demonstrate its potential advantages over LDL-C: superior risk predictor, fasting not required.

• Therefore, it was decided to increase its profile in the guidelines. Non-HDL-C would be particularly useful where apo B is unavailable and where TG ≥ 1.5 mmol/L.




High risk recommendations1. High risk is defined in those subjects who have clinical atherosclerosis, diabetes >15

years duration and age >30 years, or age >40 years with diabetes, or adjusted Framingham Risk Score of ≥20%. (Strong Recommendation, High-Quality Evidence).

We now include abdominal aortic aneurysm, high risk kidney disease (eGFR < 45) and high risk hypertension in this category (Strong Recommendation, Moderate-Quality Evidence).

2. Treatment target for LDL-C ≤ 2.0 mmol/L or ≥ 50% reduction for optimal risk reduction.

(Strong Recommendation, Moderate-Quality Evidence).

3. Apo B (≤ 0.80 g/L) or non-HDL-C (≤ 2.6 mmol/L) be considered as alternative (Strong Recommendation, High-Quality Evidence).




High risk: values and preferences

• Our decision to add chronic kidney disease (eGFR < 45) to the high risk category was based on significant emerging epidemiology data and the recently published Study of Heart and Renal Protection (SHARP).

• The treatment of dyslipidemia in subjects on hemodialysis remains controversial and individual judgment is required.




Risk stratification by Framingham Risk Score (FRS) and phenotype2012 CCS Dyslipidemia Guidelines Update



Risk stratification for intermediate risk subjects2012 CCS Dyslipidemia Guidelines Update



Levels of risk - Practical tips:

• LDL-C remains the primary target in the guidelines. Clinicians would be encouraged to be familiar with the use of LDL-C and one of the two alternate targets.

• We do not advocate using all 3 indices regularly or testing for LDL-C, non-HDL-C and apo B concurrently in subjects.

• For those who have apo B available and are comfortable with using it, there are advantages that were previously addressed.




Summary of treatment thresholds and targets based on Framingham Risk Score (FRS), modified

by family history






Secondary TestingTodd J Anderson MD



Secondary Testing

1. We recommend secondary testing for further risk assessment in “intermediate risk” (10-19% FRS after adjustment for family history) subjects who are not candidates for lipid treatment based on conventional risk factors or for whom treatment decisions are uncertain.(Strong Recommendation, moderate quality evidence)




Secondary Testing

2. We suggest that secondary testing may be considered for a selected subset of “low to intermediate risk” (5-9% FRS after adjustment for family history) subjects for whom further risk assessment is indicated, e.g. strong family history of premature CAD, abdominal obesity, South Asian ancestry or impaired glucose tolerance.(Weak recommendation, low quality evidence)




Optional Biomarkers for Further Risk AssessmentBiomarker Indications for testing Frequency of testing Normal Range

Lp(a) • Further risk assessment particularly in individuals with a family history of premature CVD

• Genetically determined risk factor

• Repeat testing not required

< 30 mg/dl

(< 300 mg/L)

hsCRP • Men > 50y and women > 60y who are not candidates for statin Rx based on conventional risk factors

• q 3 y from age 50 y (M) 60 y (F)• If > 2.0 mg/L, repeat in 2-4 wk,

use lower value for risk assessment

< 1.0 lowest risk> 2.0 increased risk

> 3.0 high risk

A1C • Further risk assessment in selected subjects with FPG >5.6 mmol/L

• q 1 - 5 y • more frequently if weight gain

or incr FBG

< 5.5% low risk5.5-6.0 % mid risk6.0-6.5 % high risk

> 6.5 % diabetes

Urinary Alb/Cr • T2DM • poorly controlled HTN• Selected patients who are not

candidates for statin Rx based on conventional risk factors

• q 1 y for patients with T2DM or poorly controlled HTN

< 3 mg/mmol




Choose a test appropriate for the individual patient (not multiple tests)

• Lp(a): 30-70 mg/dl confers ~ 1.3X increased risk; > 80 mg/dl ~ 1.5X increased CVD risk

• hsCRP > 2 mg/dl is associated with ~ 1.5 to 2.0 X increased CVD risk

• HbA1c 6.0 – 6.5 % is associated with ~ 1.5 – 1.8 X increased CVD risk

• Microalbuminuria is associated with ~ 1.5 X increased CVD risk




Optional Noninvasive Tests for Further Risk AssessmentNoninvasive test

Indications for testing Normal Range Frequency of testing

Graded exercise stress test

• Selected asymptomatic adults with CVD risk factors especially those who are embarking on a vigorous exercise program

• Selected adults in the intermediate risk category

Duke Scorea

Low risk ≥ +5Moderate risk -10 to +4High risk ≤ -11

q 3-10 y or if symptoms develop

Carotid imaging

Selected asymptomatic adults in not candidates for statin Rx based on conventional risk factors. Only in centres with expertise

CIMT <1.0 mmNo visible plaqueb

q 5-10 y as indicated for reassessment of risk

ABI Selected asymptomatic adults, not candidates for statin Rx based on conventional risk factors (particularly smokers, diabetes)

ABI 1.0-1.3c q 5-10 y as indicated for reassessment of risk or if symptoms develop

CAC Selected asymptomatic adults who are not candidates for statin Rx based on conventional risk factors

CACLow risk 0Increased risk 0 – 100High risk 100-300d

Very high risk > 300e

CAC = 0 q 10y where clinically indicated

CAC = 0 – 100 q 3-5y if Rx is deferred




Choice & Interpretation of Noninvasive TestsGXT: May be indicated for sedentary patient wishing to start exercise program; note that CAD risk is also increased in subjects with low exercise capacity (< 6 METS)

ABI: Consider for patient with suspected PAD. ABI < 0.90 is an indication for intensive statin therapy

Carotid IMT: Each 0.1 mm increase in CIMT is associated with a 10% increased risk for MI and a 13% increased risk for stroke. Visible arterial wall plaques defined as a CIMT > 1.5 mm or CIMT values > 75% for age and sex are considered as evidence of subclinical atherosclerosis and an indication for statin therapy

Coronary artery calcium: Highest incremental value but radiation exposure and not yet generally available. CAC > 100 is generally an indication for statin Rx. CAC > 300 places patient in very high risk category (10 y risk of MI/CV death = 28%)





Eva Lonn




Novel markers of atherosclerotic risk

Lorenz et al. Circ 2007 115:459

Met-analysis of 37197 subjects8 studies, 12 pubs of IMT



IMT and Discrimination, Reclassification

• USE-IMT meta-analysis– 15 large cohort studies– 45,000 subjects– 4007 first MI or stroke– C-statistic 0.757 and not changed with IMT– NRI significant but 0.8% given sample size– NCRI for intermediate risk 3.6%

Den Ruijiter JAMA 2012; 308:796-





Coronary Artery CalciumDue to atherosclerosis

Related to age and risk factors

Not related to stenosis but is related to plaque volume

Can be detected by EBCT or MDCT

Radiation dose is moderate (0.5-1.5 mSev and acquisition very quick

Variance about 40% for repeated measures



Coronary calcium score – Prevalence

Tota-Maharaj EHJ 2012;33:2955


aSx group 44,052CAC related to all cause mortality across age range



Coronary calcium score - Prognosis MESA – 6722 subjects162 events

HR 7.08 for majorCoronary eventWith CAC >100


Detrano NEJM 2008;356:1336



Comparison of novel risk markers

Yeboah JAMA 2012;308:788

MESA1330 IR subjectsCAC, IMT, CRP, FH and ABI

123 CVD events

Carotid IMT not associated with events while others were

CAC was best






Health BehavioursGillian M. Yates, MN NP



Search Strategy • Update on international and US dietary guidelines for the treatment

of dyslipidemias and cardiovascular diseases since 2007• Update on physical activity guidelines for the treatment of

dyslipidemias and cardiovascular diseases since 2007• Three primary questions to be addressed:

1. Effect of diets and macronutrient composition in interventions ≥ 8 weeks in duration

2. Effect of physical activity in interventions ≥ 8 weeks3. Effect of health behaviour changes (i.e., lifestyle modification

with combined dietary and exercise, with or without weight loss) in interventions ≥ 8 weeks




Lifestyle Modification

• Health behaviour interventions are the cornerstone of cardiovascular disease management and prevention– Diet– Exercise– Alcohol intake– Cigarette smoking– Stress and mental health issues




Table 7. Expected Benefit of Health Behaviour ChangesIntervention (minimal dose for effect) Expected OutcomeDietary cholesterol intake98 < 300 mg/day (NCEP step I diet) < 200 mg/day (NCEP step II diet)

↓ LDL-C10-12%12-16%

Saturated fats < 7% of daily caloric intake107 ↓ LDL-C 5-10%; ↓ CVD mortality 14%

Phytosterols 1-2 g/day100 ↓ LDL-C 5-8%

Soy proteins with isoflavones 25g/day101 ↓ LDL-C 3-5%

Viscous fibre 10 g/day102 ↓ LDL-C 3-5%

Nuts 30-67 g/day103 ↓ LDL-C 5-7%, ↓ TG 5-10%

Portfolio type diet104 ↓ LDL-C 8-14%

Mediterranean type diet105 ↓ LDL-C 5-10%; ↓ CVD mortality

DASH (Dietary Approaches to Stop Hypertension) diet106

↓ CVD mortality in those with hypertension




Table 7. Expected Benefit of Health Behaviour Changes

Intervention (minimal dose effect) Expected Outcome

Moderated Alcohol intake 1-2 drinks/day ↑ HDL 5-10%, ↓ CVD events

Weight loss and reduction of abdominal obesity42 ↓ LDL-C, ↑ HDL, ↓ TG, 5-10% of body weight loss ↓cardiometabolic risk

Omega -3 - 2-4 g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)/day ↓ TG 25-30% in pts. with ↑ TG

Exercise109,110 30-60 min/day moderate to vigorous intensity ↑ HDL 5-10%, ↓ CVD events

Smoking cessation ↑ HDL, ↓ CVD events




RecommendationsWe suggest that all individuals be encouraged to adopt healthy eating habits to lower their cardiovascular (CVD) risk: 1.Moderate energy (caloric) intake to achieve and maintain a healthy body weight 2.Emphasize a diet rich in vegetables, fruit, whole-grain cereals, and polyunsaturated and monounsaturated oils, including omega-3 fatty acids particularly from fish 3.Avoid trans fats, limit saturated and total fats to < 7% and < 30% of daily total energy (caloric) intake, respectively 4.Increase daily fibre intake to > 30 g5.Limit cholesterol intake to 200 mg daily for individuals with dyslipidemia or at increased CVD risk (Conditional Recommendation, Moderate-Quality Evidence)




Recommendations

We recommend the Mediterranean, Portfolio or DASH diets to improve lipid profiles or decrease CVD risk

(Strong Recommendation, High-quality Evidence) and for cholesterol lowering consider increasing

phytosterols, soluble fibre, soy and nut intake (see Table 7)




Recommendations• We recommend that adults should accumulate at

least 150 min. of moderate-to-vigorous-intensity aerobic physical activity per week, in bouts of 10 min or more to reduce cardiovascular disease risk.

(Strong Recommendation, High-Quality Evidence)

• We recommend smoking cessation (Strong Recommendation, Moderate-Quality Evidence)

• and limiting alcohol intake to 30 g or less per day (1-2 drinks)

(Conditional Recommendation, Moderate-Quality Evidence)






Statin Intolerance Glen J. Pearson PharmD



Statin Intolerance Recommendations1. Because overall risk/benefit favours therapy in patients

meeting criteria for lipid lowering therapy and cardiovascular risk reduction, we recommend that:

i. despite concerns about a variety of other possible adverse effects, all purported statin-associated symptoms should be evaluated systematically, incorporating observation during cessation, reinitiation (same or different statin, same or lower potency, same or decreased frequency of dosing) to identify a tolerated, statin-based therapy for chronic use; and(Strong Recommendation, Very Low-Quality Evidence)




Statin Intolerance Recommendations1. Because overall risk/benefit favours therapy in patients

meeting criteria for lipid lowering therapy and cardiovascular risk reduction, we recommend that: (cont)

ii. Statins not be withheld on the basis of a potential, small risk of new-onset diabetes mellitus emerging during long-term therapy (Strong Recommendation, Very Low-Quality Evidence)

2. We do not recommend vitamins, minerals, or supplements for symptoms of myalgia perceived to be statin-associated

(Strong Recommendation, Very Low-Quality Evidence).




Statin Intolerance Practical tip• Patients should be advised to stop statin therapy and contact the

prescribing health care provider if worrisome symptoms develop.

• The amount of effort spent persevering with statin therapy in subjects with adverse effects should be directly related to the level of risk for an individual patient.

• In those at highest risk all options should be exercised before changing to alternative lipid-lowering therapy or withdrawing all lipid-lowering treatment. Lower dose combination therapy remains an option for these subjects.




Statin Intolerance Practical tip• Strong emphasis should be put on a more aggressive

nonpharmacologic approach such as diet modulation and exercise.

• For subjects at lower risk who do not tolerate statin therapy, a re-evaluation of the need for lipid lowering therapy should precede a change to alternative therapy because outcomes studies are not as robust.




Management Algorithm for Statin-Induced Muscle Symptoms

Mancini GBJ, Baker S, Bergeron J, et al. Can J Card 2011; 27:635–662




Canadian Lipid Guidelines: Summary• FRS doubled with positive family history• Primary target: - absolute LDL-C ≤ 2 mmol/L

- relative decrease in LDL-C ≥ 50%

• Alternates: - non-HDL-C ≤ 2.6 mmol/L - apo B ≤ 0.8 g/L

• 5-9% risk: - monitor yearly• Secondary markers:

- biochemical: Lp(a), hsCRP, HbA1c, ACR- non-invasive: GXT, IMT, ABI, CAC

• Lifestyle recommendations• Statin intolerance recommendations




Case DiscussionsJean Grégoire MD




Case # 1



Case # 1

• 54 year old woman• Treated hypertension x 12 years, otherwise healthy• Non-smoker, non-diabetic, no relevant family history• BP 132/90, TC 5.4, HDL 1.3, LDL 3.3




What is her FRS?

1. < 5 %2. 5-9%

3. 10-19%4. >20%


FRS is 10%LDL is 3.3



Should she receive a statin?

1. Yes2. No3. I need more

information in order to decide




High risk hypertension (ASCOT)

HT plus any 3 of these risk factors equates to high risk:

• Male gender• Age >55• Smoking• LVH• TC:HDL > 6• Family history premature CHD• Abnormal ECG• Microalbuminuria


ASCOT Primary Endpoint: Non-fatal MI and Fatal CHD

0

1

2

3

4

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Years

Cu

mu

lati

ve I

nci

den

ce (

%)

36% reduction

HR = 0.64 (0.50-0.83)

Atorvastatin 10 mg Number of events 100

Placebo Number of events 154

p=0.0005

Sever PS, Dahlöf B, Poulter N, Wedel H, et al, for the ASCOT Investigators. Lancet 2003;361:1149-58

0

1

2

3

4

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Years

Cu

mu

lati

ve I

nci

den

ce (

%)



Case # 1 – Additional information

• Weight 66 kg, BMI 25.8, waist circumference 85 cm• FPG 5.3, A1c 0.058• hsCRP 1.2• Creatinine 168, eGFR 40




Case # 1

• She has chronic kidney disease (eGFR < 45)This is considered a high risk equivalent

• She should therefore be considered for statin therapy to a target LDL < 2.0




Alberta Kidney Disease NetworkTonelli et al. Lancet 2012




0 1 2 3 4 5 Years of follow-up

0

5

10

15

20

25 Pr

opor

tion

suffe

ring

even

t (%

)

Risk ratio 0.83 (0.74-0.94) Logrank 2P=0.0021 Placebo

Simv/Eze

SHARP: Major Atherosclerotic Events in Patients with CKD2012 CCS Dyslipidemia Guidelines Update



Case # 1

• She is started on atorvastatin 20 mg daily• LDL falls to 2.4 and the drug is well-tolerated• The dose is titrated to 40 mg daily but she develops

bothersome muscle aches with a CK of 450• Renal function remains stable




Muscle aches on atorvastatin 40 mg, suboptimal LDLWhat next?

1. Reduce atorvastatin to 20 mg daily, accept LDL 2.42. Change to rosuvastatin 10 mg and titrate as tolerated3. Change to simvastatin 20 mg and add ezetimibe 10 mg4. Reduce to atorvastatin 20 mg and add ezetimibe 10 mg5. Leave atorvastatin at 40 mg and add coenzyme Q106. Other


While the correct answer is 4, 2 and 3 could be used as second choices.



Canadian Journal of Cardiology 2011; 27:635-662




Non-Statin Lipid Lowering Strategies

EzetimibeLowers LDL 15-20%Well toleratedMay be added tolow dose statin

Bile acid sequestrantsLowers LDL 15%May prevent diabetesColesevalam bettertolerated

Ezetimibe + Bile acid sequestrant

40-45% LDL reduction

Fibrates TG LDL little change ? Benefit when HDL low

Niacin Flushing/pruritus may limit

tolerance Lowers LDL 20% TG40%, HDL30%




What if she was already on hemodialysis? Should she receive lipid-lowering therapy?

1. Yes2. No

3. Uncertain




Risk ratio & 95% CIPlaceboSimv/Eze

Simv/Eze better Placebo better

(n=4620)(n=4650)

Non-dialysis (n=6247) 296 (9.5%) 373 (11.9%)

Dialysis (n=3023) 230 (15.0%) 246 (16.5%)

Major Atherosclerotic Event 526 (11.3%) 619 (13.4%) 16.6% SE 5.4 reduction (p=0.0021)

1.0 1.2 1.4 0.8 0.6

SHARP: Major Atherosclerotic Events by renal status

No significant heterogeneity between non-dialysis and dialysis patients (p=0.25)

The treatment of dyslipidemia in subjects on hemodialysis remains controversial and individual judgment is required.





Case # 2



Case # 2

• 36 year old South Asian man• Non-smoker, non-diabetic, normotensive• Father had MI at age 46• BP 128/84, TC 5.8, HDL 1.0, LDL 4.1




What is his FRS?

1. < 5 %2. 5-9%

3. 10-19%4. >20%


FRS is 3.9%Family history FRS 7.8%

LDL is 4.1



Ten-Year vs. Lifetime Risk

70

60

50

40

30

20

10

050 60 70 80 90

69

5046

36

5

60

50

40

30

20

10

0

Men(n = 3564)

Women

(n = 4362)

Adjusted cumulative incidence of CVD (%)

50 60 70 80 90

≥2 Major RFs1 Major RF

≥1 Elevated RF≥1 Not optimal RF

All optimal RFs

70

50

39

27

8

Attained age (years)

Lloyd-Jones DM et al. Circulation. 2006;113:791-8.




Lifestyle Recommendations

• Mediterranean, Portfolio or Dash diets: including foods high in plant sterols, soy protein, high viscous fiber, omega 3 fatty acids and nuts

• Moderate alcohol intake 1-2 drinks/day• 150 min of moderate to vigorous aerobic activity per week• Healthy body weight with BMI 20-25 kg/m(2)• 0-5-30 approach to counselling:

– 0 cigarettes– 5 servings of fruits/vegetables/day– 30 min of exercise per day




Should he receive a statin?

1. Yes2. No3. I need more information in

order to decide





• Weight 65 kg, BMI 22.5, waist circumference 80 cm• FPG 6.2, A1c 0.062• Creatinine 78, eGFR 120





1. Yes2. No3. I need more information

in order to decide




Case # 2

• 36 year old South Asian man• Non-smoker, non-diabetic, normotensive• Father had MI at age 46• BP 128/84, TC 5.8, HDL 1.0, LDL 4.1• Weight 65 kg, BMI 22.5, waist circumference 80 cm• FBS 6.2, A1c 0.062• Creatinine 78, eGFR 120




Statins and low risk individuals

CTT Lancet 2012;379




Case # 2

• He is at low to intermediate risk (7.8%)• He is South Asian, indicating higher risk than suggested by FRS• LDL is fairly high at 4.1, though not > 5.0• Secondary testing is reasonable to further risk stratify

• He has dysglycemia, with an abnormal A1c, which increases his risk by 1.5 -2 fold

• He can therefore be considered for statin therapy to a target LDL < 2.0 or a 50% reduction from baseline




Case # 3




Case # 3

• 56 year old white man• Non-smoker, non-diabetic, normotensive• No relevant family history• BP 124/78, TC 5.6, HDL 1.1, TG 3.2, LDL 3.0




What is his FRS?

1. < 5 %2. 5-9%

3. 10-19%4. >20%


FRS is 15.6%LDL is 3.0




1. Yes2. No3. I need more

information in order to decide





• Weight 86 kg, BMI 30, waist circumference 104 cm• FBS 5.4, Creatinine 85, eGFR 90





1. Yes2. No3. I need more information

in order to decide




Is secondary testing necessary?

1. Yes2. No3. Uncertain




If secondary testing is necessary, which test would you consider?

1. hsCRP2. HbA1c3. Urinary protein4. Stress testing5. Carotid ultrasound6. Ankle brachial index7. Coronary calcium score8. Other




Case # 3: Secondary testing is not required

• 56 year old white man• Non-smoker, non-diabetic, normotensive• No relevant family history• BP 124/78, TC 5.6, HDL 1.1, TG 3.2, LDL 3.0• Weight 86 kg, BMI 30, waist circumference 104 cm• FBS 5.4, Creatinine 85, eGFR 90




Case # 3 – Options other than secondary testingThe role of non-HDL

• For patients with FRS 5-19% with LDL<3.5, one can consider assessment of apoB or non-HDL

• Non-HDL = TC minus HDL• No fasting required, no extra cost, immediately calculated

from any full lipid profile • This patient’s non-HDL = 5.6 – 1.1 = 4.5• If non-HDL > 4.3 with LDL < 3.5, can consider statin therapy




Thank You and Questions

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