abc’s of cvd risk assessment,web.brrh.com/msl/grandrounds/2018/grandrounds_120418... ·...

ABC’s of CVD Risk Assessment,

BP, & Cholesterol Guidelines

(The Juice was Worth The Squeeze)

Roger S. Blumenthal, MD, FACC, FAHA The Kenneth Jay Pollin Professor of Cardiology

Director, The Johns Hopkins Ciccarone Center for the

Prevention of Heart Disease

Disclosures: None

Different Types of Prevention

• Primordial: Prevention of risk factor (RF)

development

• Primary: RF modification to delay ASCVD

onset

• Secondary: Initiation of Rx to reduce

recurrent events in patients with ASCVD

ASCVD = atherosclerotic cardiovascular disease

Top 10 Take Home Messages of ’18 Guidelines

1. Emphasize heart-healthy lifestyle Healthy lifestyle reduces risk at all ages reduces risk factor development 20 to 39 yrs: assessment of lifetime risk facilitates clinician–patient risk discussion & emphasizes intensive lifestyle efforts primary intervention for Metabolic Syndrome

Top 10

2. If clinical ASCVD, reduce LDL-C with high-intensity statin or max tolerated statin The more LDL-C is reduced the greater the risk reduction Use max tolerated statin to lower LDL-C by ≥50%

Top 10 Take Home Messages

Top 10

3. Very high-risk ASCVD: use LDL-C threshold of 70 mg/dL to consider nonstatin

• Very high-risk: multiple major ASCVD events or 1 major event +

high-risk conditions

• Reasonable to add ezetimibe to max. tolerated statin when LDL-C remains ≥70

• If LDL-C remains ≥70 on max. statin + ezetimibe adding PCSK9i is reasonable

* long-term safety (>3 years) & cost-effectiveness less certain


Top 10

4. Severe primary hypercholesterolemia (LDL-C ≥190) begin high-intensity statin • If LDL-C ≥100 ezetimibe reasonable • If LDL-C on statin + ezetimibe remains ≥100 & other risk factors consider PCSK9i, though long-term safety (>3 yrs) & economic value less clear


Top 10

5. 40 to 75 y/o with Diabetes & LDL-C ≥70 moderate-intensity statin If diabetes + multiple risk factors or 50-75 y/o reasonable to reduce LDL-C ≥50% with high-intensity statin


CAC beyond guidelines for the Statin Reluctant Adult with Diabetes

• Adults with Diabetes • 6751 participants from MESA, 881

diabetes

• CAC 0, 55% vs. 37%

• 11 years of follow-up

12/4/2018 Malik et al. JAMA Cardiol

2017;2:1332 9

Top 10

6. 40 to 75 y/o evaluated for primary prevention clinician–patient risk discussion before starting statin Review: • Estimated 10-yr risk, major risk factors, & risk- enhancing factors • Potential benefits of lifestyle + statin • Potential adverse effects & drug interactions + costs • Patient Preferences & values in shared decision- making


Top 10

7. 40 to 75 y/o without diabetes & LDL-C ≥70 + 10-yr risk of ≥7.5% start moderate-intensity statin if risk discussion favors Rx Risk-enhancing factors may be used in shared decision making If risk status remains uncertain consider coronary artery calcium (CAC) to resolve risk uncertainty


Top 10

8. 40 to 75 y/o without diabetes & 10-yr risk of 7.5-19.9% (intermediate risk), risk-enhancing factors favoring statin Rx include: • Family history premature ASCVD • Elevated LDL-C ≥160 (persistent) • Metabolic Syndrome •.Chronic kidney disease • Preeclampsia or premature menopause (age <40 yrs) • Chronic inflammatory disorders (e.g., rheumatoid arthritis, psoriasis, SLE, or chronic HIV) • High-risk ethnic groups (e.g., South Asian) • Triglycerides ≥175 mg/dL (persistent)


CAC beyond guidelines

• Rheumatoid arthritis

• Patients 46-60 yo, without clinical ASCVD

• 60% CAC = 0

• Swiss HIV cohort study

• ≥ 45 years old, without clinical ASCVD, FRS 9.4%

• 47% CAC = 0

• Psoriatic arthritis

• Mean age 51 years old, FRS 9%

• 58% CAC = 0

12/4/2018

Mansouri et al. JAMA Dermatol 2016;152:1244

Karpouzas et al. Rheumatology 2018;57:1080

Tarr et al. Eur Heart J 2018;39:2147

13

Top 10

8. 40 to 75 y/o: without diabetes + 10-yr risk of 7.5-19.9% (intermediate risk), risk-enhancing factors favoring statin Rx include:

if measured in selected individuals:

• Apolipoprotein B ≥130 mg/dL • hsCRP ≥2.0 mg/L • Ankle-brachial index <0.9 • Lipoprotein (a) ≥50 mg/dL or 125 nmol/L


Top 10

9. 40 to 75 y/o without diabetes & LDL-C ≥70 & 10-yr ASCVD risk of ≥7.5-19.9%, if statin decision uncertain consider CAC

• If CAC = 0, statin may be withheld or delayed, except in cigarette smokers, those with diabetes, & those with strong family history of premature ASCVD • CAC 1 to 99 favors statin • If CAC ≥100 or ≥75th%, statin indicated unless otherwise deferred by risk discussion outcome


CAC beyond guidelines

• Age-driven risk scores • MESA, 45-84 yrs old • Median f/u 8.5 yrs

• CHD events • One in seven patients

• Age 45-54, CAC >0 • Age 75-84, CAC=0

12/4/2018

Tota-Maharaj et al. Mayo Clinic Proc 2014;89:1350

16

Top 10

10. Assess adherence & % response to LDL-C–lowering med(s) + lifestyle changes with repeat lipid measurement 4-12 weeks after Rx initiation or dose adjustment repeated q3-12 months • Define responses to lifestyle + statin by % LDL-C reductions compared with baseline

• ASCVD at very high-risk, triggers for adding nonstatin drug defined by threshold LDL-C levels ≥70 on maximal statin (use Martin/Hopkins LDL-C)


2013 ACC/AHA (U.S) 10-yr CVD

risk score (ages 40-79 yrs)

A: Assessment of Risk Step 1: Calculate 10-yr risk for MI/CVA

Goff D et al. Circulation 2014.

• Based on multiple cohorts;

gender & race-specific

• CVA included in addition to MI

& CHD mortality

A : Risk Assessment: Can we

improve it?

• ASCVD

– Fatal or nonfatal MI

or stroke

Current Risk Assessment

• Global composite CVD

– MI, stroke,

– Heart Failure, Afib

– revascularization

Future Comprehensive

Risk Assessment ?? ?

Performance of Pooled Cohort Equations in Diverse Population Samples: Predictable

Over- Estimate

Risk

Under- Estimate

Risk

Low SES, HIV,

Inflammatory dz

High SES,

engaged patients

Broad US

Clinical

Population

Reasonable

Calibration

Clinician-Patient Discussion

Estimated 10-y ASCVD Risk

Pooled Cohort Equations

• Overestimate risk • In 10-year ASCVD risk >10%

• Higher socio-economic status

• Receiving preventive care

• Underestimate risk • Lower SES

• Risk enhancing factors

12/4/2018 Differing impact of Cigarettes, Weight, Dietary Knowledge 21

Estimate Absolute 10-year ASCVD Risk

Low Risk 0 - <5%

High Risk ≥20%

Intermediate Risk 7.5% - <20%

Lifestyle and drug therapy

Lifestyle modification

Borderline Risk 5% - <7.5%

Clinician-patient discussion considering risk-enhancing factors and net benefit of therapy

Refining Risk Estimates for Individual Patients

2009: Origin of Power of Zero

• The PIONEERS of this approach since 2011:

Power of Zero – CAC A Bayesian Approach

• CAC is helpful

• Intermediate risk asymptomatic patients

• Maybe low risk symptomatic patients

• CAC is NOT helpful

• Very low risk asymptomatic patients

• Higher risk symptomatic patients

• Cost saving and less downstream testing

Refining Risk Estimates for Individual Patients

Nasir K et al., MESA Study, JACC 2015

Example: MESA Study

7.5% 10-yr risk

Threshold for considering statin

CAC for “De-Risking” Negative Risk Markers for CVD: MESA

Blaha et al. Circulation

2016; 33:849-858

A: Assessment of Risk When decisions are as uncertain as a flip of a coin

Top 7 Indications for

CAC Testing (primary prevention)

1. “Intermediate” Risk Patient

– ASCVD 5-20%, Risk Uncertain

– Family History, lower risk diabetes

2. Statin Reluctant Pt

3. Statin Intolerant Pt

4. Decisions for Non-Statin Rx

5. Decisions For Aspirin Rx

6. Low Risk Chest Pain Syndrome

7. MOTIVATION!

ASPIRIN therapy

PRIMARY Prevention

A: Antiplatelet therapy

Aspirin for Primary Prevention of ASCVD:

2014 Meta-analysis

ASCVD Events – 10% ↓

RR 0.90 (95% CI 0.85, 0.95)

Major Bleeding – 55% ↑

RR 1.55 (1.35, 1.78)

NNT to prevent 1 major

ASCVD event over mean f/u

of 7 years = 284.

NNH to cause 1 major bleed =

299

Xie M et al. PLoS ONE 2014; 9(10): e90286

NNT = number needed to treat; NNH = number need to harm

Aspirin in Primary Prevention:

ASCEND

• Adults with diabetes, but no CVD

• 15,480 participants followed for mean of 7.4 yrs

• Randomized to aspirin 100 mg daily vs. placebo

• Primary efficacy outcome was 1st serious vascular event

• MI, stroke or TIA, or death (excluding any ICH)

• Primary safety outcome was 1st major bleeding event

• ICH, GI, or other serious bleeding

Aspirin in Primary Prevention:

ASCEND

BENEFIT:

Vascular Events:

RR 0.88(.79-.97)

p=0.01

• Aspirin group

[8.5%]

vs.

• Placebo group

[9.6%]

A: Aspirin in Primary Prevention

ASPREE

• Adults in Australia (>70 y.o) & U.S. (>65 y.o among

Blacks/Hispanics)

• 19,114 participants – excluded those with CVD, dementia,

disability - followed for mean of 4.7 yrs

• Randomized to EC aspirin 100 mg daily vs. placebo

• Primary endpoint: death, dementia, or persistent physical disability

• Secondary endpoint included individual components of primary end

point & major hemorrhage

A: Aspirin in Primary Prevention

ASPREE

Antiplatelet/Anti-thrombotic

Conclusions

• Primary Prevention - ??

– Low dose aspirin if sufficiently high risk for ASCVD &

low bleeding risk

• Secondary Prevention

– Low dose aspirin

– DAPT after ACS for 12 months

– consider longer DAPT for high risk patients at low

bleeding risk

– May be future role for low dose anti-thrombotic +

aspirin in PAD patients

B: Blood Pressure Control

Importance of BP Control in Preventing CVD

• 2017 AHA/ACC (U.S) Blood

Pressure Guidelines SPRINT trial • Compared 2 strategies of BP management:

• Target of <140/90 vs <120/80

N Engl J Med 2015; 373:2103-2116 For most, BP target is <130/80

• Difference of 13 mmHg SBP between Rx groups

– 3 vs. 2 BP meds

• 25% relative risk reduction primary outcome

– ARR 1.6%, NNT 61

• 27% relative risk reduction all-cause mortality

– ARR 1.2%, NNT 90

• Rx effect similar across all 6 pre-specified subgroups

– CV disease, CKD, sex, race, age (>75 yrs), baseline SBP

• Serious adverse events

– Increased hypotension, electrolyte abnormalities, AKI, & syncope

– Not injurious falls

Summary of SPRINT findings

What is the OPTIMAL SBP goal in this patient?

<150

<140

<130

<120

65 year-old man with HTN, obesity (BMI 31), OSA, prediabetes self-referred for CV evaluation. Mean BP in office & at home on HCTZ 25mg daily is 155/76.

Lifestyle therapy for BP reduction

• Sodium restriction ↓ BP 2-15 mm Hg

– ~2000 mg/day

• Weight loss ↓ BP 5-20 mm Hg/10 kg weight loss

• Moderately intense ↓ BP 4-10 mm Hg

physical activity

• Reduction of alcohol ↓ BP 2-5 mm Hg

Chobanian et al., JAMA, 2003;289:2560-72 (JNC 7 Report)

Major Points from JNC 8:

General population, age ≥60 – Rx if SBP ≥150 mmHg for goal SBP <150 mmHg

(strong recommendation, grade A)

DM, age ≥18 – Treat if SBP is ≥140 for

goal <140/90 (expert opinion, grade E)

(JAMA 2014;311(5):507-20)

Definition of High BP

COR LOE Recommendation for Definition of High BP

I B-NR

BP should be categorized as normal, elevated, or

stage 1 or 2 hypertension to prevent and treat high

BP.

BP Category SBP DBP

Normal <120 mm Hg and <80 mm Hg

Elevated 120–129 mm

Hg

and <80 mm Hg

Hypertension

Stage 1 130–139 mm

Hg

or 80–89 mm

Hg

Stage 2 ≥140 mm Hg or ≥90 mm Hg

Prevalence of Hypertension Based on

2017 ACC/AHA Guidelines

Messerli and Bangalore. J Am Coll Cardiol 2018;71:119-121 Muntner et al. J Am Coll Cardiol 2018;71:109-118.

• Prevalence

– Increased to 46%

– 103 million people

– Additional 31 million

• Pharmacologic Rx

– Increased to 36%

– 82 million people

– Additional 4.2 million

2017 Hypertension Guidelines

C: Cholesterol Management

Lower LDL-C –> Lower

CHD Risk

But…35% of Heart Disease

occurs in those with Total

Chol <200 mg/dL

Cholesterol Management 4 “Statin Benefit Groups” in 2013 ACC/AHA

Lipid Guidelines – still need Risk Discussion

Stone NJ, et al. JACC. 2014;63(25 Pt B):2889-2934.

Intensity of LDL-C Reduction

COR LOE Recommendations

I A

If <75 y/o with clinical ASCVD, high-intensity statin

should be initiated or continued with aim of >50%

LDL-C reduction

I A

If clinical ASCVD & high-intensity statin is

contraindicated or statin-associated side effects

moderate-intensity statin initiated or continued

with aim of > 30% LDL-C reduction

Secondary ASCVD Prevention

Very High Risk ASCVD: Ezetimibe


IIa B-R

Clinical ASCVD on maximally tolerated statin & at

very high risk with LDL-C >70: reasonable to add

ezetimibe


Possible PCSK9i Use in Very High Risk ASCVD


I B-NR

If clinical ASCVD + very high risk & considered for

PCSK9 inhibitor, Rx should include maximally

tolerated statin + ezetimibe

IIa ASR

If clinical ASCVD + very high risk on maximally

tolerated Rx with LDL-C >70 or non-HDL>100,

reasonable to add PCSK9i after discussion about net

benefit, safety, & cost


ARR 2.2%,

NNT 45

ARR 6.3%,

NNT 16


LDL-C Threshold for Additional Rx/HFrEF


IIb B-R If clinical ASCVD & on maximally tolerated statin

Rx with LDL-C >70, reasonable to add ezetimibe

IIb B-R

In HFrEF due to ischemic heart disease, life

expectancy >3 yrs, & not already on statin, may

consider moderate-intensity statin to reduce risk

Statin Therapy in Patients with Heart Failure

• Two RCTs (CORONA, GISSI HF) of statin therapy in heart failure patients failed to meet their primary end point.1,2 Both studies were notable for high overall and cardiovascular mortality rates, with MI occurring in a small minority.

• Post hoc analyses from CORONA showed that patients randomized to rosuvastatin (10 mg daily) with less advanced HF with reduced ejection fraction (lowest tertile of NT-proBNP) had a significant reduction in the primary outcome, but no benefit was seen among patients with more advanced HF.3

• A subsequent patient-level analysis that pooled data from both these trials and accounted for competing causes of death showed a significant 19% reduction in the risk of MI with rosuvastatin in patients with ischemic HF, although the ARR was small.4

1. Kjekshus J, et al. N Engl J Med. 2007;357:2248-61 2. Tavazzi L, et al. Lancet. 2008;372:1231-9. 3. Cleland JG, et al. J Am Coll Cardiol.

2009;54:1850-9. 4. Feinstein MJ, et al. Eur J Heart Fail. 2015;17:434-41.

FOURIER Trial Design Evolocumab in secondary ASCVD prevention

Evolocumab SC 140 mg Q2W or 420 mg QM

Placebo SC Q2W or QM

LDL-C ≥70 mg/dL or

non-HDL-C ≥100 mg/dL

Follow-up Q 12 weeks

Screening, Lipid Stabilization, and Placebo Run-in

High or moderate intensity statin therapy (± ezetimibe)

27,564 high-risk, stable patients with established CV disease (prior MI,

prior stroke, or symptomatic PAD)

RANDOMIZED

DOUBLE BLIND

Sabatine MS et al. Am Heart J 2016;173:94-101

FOURIER Trial

Evolocumab: LDL-C Changes

Sabatine MS et al. N Engl J Med 2017;376:1713-1722

FOURIER – PRIOR MI

Evolocumab Benefit by High Risk Feature

Sabatine MS et al. AHA 2017

FOURIER –

Evolocumab benefit in PAD patients

Bonaca MP et al. AHA 2017

ODYSSEY OUTCOMES

Alirocumab in secondary ASCVD

prevention

Steg G at ACC18

Orlando, FL

ODYSSEY OUTCOMES

median f/u 2.8 years

Steg G at ACC18; Orlando, FL

ODYSSEY OUTCOMES Benefit greatest with baseline LDL-C ≥100

Steg G at ACC18; Orlando, FL

Hypertriglyceridemia

Moderate & Severe HyperTG


I B-NR

If >20 y/o with moderate hypertriglyceridemia (fasting or

nonfasting TG 175-499), address lifestyle factors (obesity &

metabolic syndrome), secondary factors (diabetes, chronic

liver or kidney disease &/or nephrotic syndrome,

hypothyroidism), & medications that increase TG

IIa B-R

If 40-75 y/o with > moderate hyperTG & ASCVD risk >7.5%,

reasonable to reevaluate risk after lifestyle & secondary

factors addressed; consider persistently elevated TG as

favoring initiation or intensification of statin

Hypertriglyceridemia

Severe HyperTG


IIa B-R

If 40-75 y/o with severe hyperTG (fasting TG ≥500) &

ASCVD risk >7.5%, address reversible causes of high TG

& initiate statin

IIa B-NR

If severe hyperTG (fasting TG ≥500) & especially fasting

TG ≥1000, address other causes of hyperTG; if TG are

persistently elevated, implement very low-fat diet,

avoidance of refined carbohydrates & alcohol,

consumption of omega-3 FA, &, if necessary to prevent

acute pancreatitis, fibrate Rx

Issues Specific to Women

Pre- and Perimenopausal Issues


I B-NR

Consider premature menopause (age <40 yrs) & h/o

pregnancy-associated disorders (HTN, preeclampsia,

gestational diabetes, small-for-gestational-age infants,

preterm deliveries), when discussing lifestyle & potential

for statin benefit

I C-LD

Women of childbearing age who are treated with statin &

sexually active should use reliable contraception

I C-LD

Women with hypercholesterolemia who plan to become

pregnant should stop statin 1-2 months before attempting

pregnancy; if become pregnant while on Rx, stop statin as

soon as pregnancy discovered

Adults With Chronic Kidney Disease


IIa B-R

If 40 to 75 y/o with LDL-C 70-189 & 10-yr

ASCVD risk of >7.5%, CKD not treated with

dialysis or kidney transplantation is a risk-

enhancing factor & initiation of a moderate-

intensity statin +/- ezetimibe can be useful

IIb C-LD If on dialysis & currently on statin, reasonable

to continue

III: No

Benefit B-R

If advanced kidney disease on dialysis,

starting statin not recommended

Adults With Inflammatory Disorders or HIV


IIa B-NR

If 40 to 75 y/o with LDL-C 70-189 & 10-yr risk >7.5%, chronic

inflammatory disorders & HIV are risk-enhancing factors &

favor moderate- or high-intensity statin

IIa B-NR

If chronic inflammatory disorders or HIV, a fasting lipid profile

and assessment of risk factors can be useful as 1) guide to

benefit of statin & 2) for monitoring or adjusting drug Rx

before & 4-12 weeks after starting inflammatory disease–

modifying therapy or antiretroviral therapy

IIa B-NR

In adults with RA who undergo risk assessment with lipid

profile, useful to recheck lipids & other major risk factors 2-4

months after inflammatory disease has been controlled

Complete cessation

No environmental

tobacco smoke exposure

Goals Recommendations

Ask about tobacco use at every visit

In clear, strong, & personalized manner, advise patient

to stop smoking

Urge avoidance of exposure to second-hand smoke

Assess willingness to quit smoking

Develop plan for smoking cessation & follow-up

Provide counseling, pharmacologic Rx, & referral to

formal cessation program

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Smith SC Jr. et al. JACC 2006;47:2130-9

C: Cigarette Smoking Cessation Tobacco Cessation Recommendations

D: Diet

E: Exercise/Physical Activity

Exercise Goals And Reduce Sitting Time!

Brisk Walking

Numbers Matter: (Thresholds/Targets)

• Lower LDL-C is better with proven therapies • High intensity statin: >50% LDL-C drop

• Threshold of 70 mg/dL for non-statins: Consider Ezetimibe

1st, PCSK9i 2nd

• FH: LDL-C threshold of 100 mg/dL

• Friedewald method limitations Martin/Hopkins method

Better Guidance for Shared Decision Making/Risk Discussion • Key feature of 2013 Guidelines improved

• Better able to separate high vs very low risk

• Risk Enhancing Factors help select higher risk

• Selective Use of CAC – IIa COR

Risk Prediction: The Power of Zero

• CAC is the best tie-breaker if Uncertainty

• Personalization: identify very low risk group

• Decision aid, not screening tool

• Focus Rx on those who will benefit the most

AHA/ACC Special Report

Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease

Donald M. Lloyd-Jones, MD, ScM, FACC, FAHA; Lynne T. Braun, PhD, CNP, FAHA; Chiadi E. Ndumele, MD, PhD, FAHA; Sidney C. Smith, Jr, MD, MACC, FAHA; Laurence S. Sperling, MD, FACC, FAHA; Salim S. Virani, MD, PhD, FACC, FAHA; Roger S. Blumenthal, MD, FACC, FAHA

Published Online Ahead of Print November 10, 2018 in Circulation and JACC

High Risk Conditions that Don’t Need Risk Calculation

• Familial Hypercholesterolemia • Diabetes Mellitus, 40-75 years

Both qualify for statin Rx without a risk estimation but CAC may still be useful

Conclusions:

Primary Prevention

• Heart healthy lifestyle for all

• Global ASCVD Risk Assessment

• Ask about Family history of ASCVD, lipid disorders

• Statin: 1st line; extra focus on FH & Diabetes

• Moderate Intensity statin if sufficiently high absolute risk after Clinician Patient Risk Discussion

• CAC helps if risk assessment uncertain

Conclusions:

Secondary Prevention

• Lifestyle still important even with statin use

• Use High intensity statin

• Lower LDL-C better with proven therapies

• If very high risk & LDL-C ≥70 mg/dL despite maximal

tolerated statin, consider ezetimibe &/or PCSK9

inhibitor

The Jordan & Pippen of Preventive Cardiology – Drs. Grundy & Stone

Dr. Grundy – HS Basketball

• Teamwork makes the dream work!

Take Home Messages

1. More options in treating elevated BP, lipids, & diabetes;

pushing boundaries of how low we can go

2. Estimated 10-yr CVD risk an important additional

parameter to consider, over & above actual BP & LDL-C

3. Shared decision making & risk discussion is important

4. CAC scores help personalize risk-based Rx decisions

5. Healthy lifestyle (diet & exercise) is foundation for

prevention

Lifestyle Improvement

Ciccarone Center for

the Prevention of

Cardiovascular

Disease at Johns

Hopkins

American Heart Association

abc’s of cvd risk assessment,web.brrh.com/msl/grandrounds/2018/grandrounds_120418... ·...

Documents