Cardiovascular Update Elise McCuiston, PharmD, BC-ADM IU Health Southern Indiana Physicians

Cardiovascular UpdateElise McCuiston, PharmD, BC-ADMIU Health Southern Indiana Physicians

Disclosures

• I have no actual or potential conflicts of interest to disclose in relation to this presentation

Objectives

• Briefly review the Institute of Medicine Report (2011) guideline standards• Identify modifications in JNC8 and the impact

on hypertension management• Review the ACC/AHA Blood Cholesterol

Guidelines and related hyperlipidemia treatment• Evaluate clinical controversies surrounding

the release of both JNC8 and ACC/AHA Blood Cholesterol Guidelines

Institute of Medicine Report (2011)- Clinical Practice Guidelines We Can Trust

• CPGs (clinical practice guidelines) may reduce inappropriate practice variation, enhance translation of research to practice, and improve healthcare quality

• Lack of transparency, inconsistent methodology, failure to seek stakeholder input

• IOM recommended 8 best practice standards for developing CPGs

http://iom.nationalacademies.org/Reports/2011/Clinical-Practice-Guidelines-We-Can-Trust.aspx

Institute of Medicine Report (2011)- Clinical Practice Guidelines We Can Trust

1. Establishing transparency2. Management of conflicts of interest3. Guideline development group composition4. Clinical practice guideline- systematic review intersection5. Establishing evidence foundations for and rating

strength of recommendations6. Articulation of recommendations7. External review8. Updating

http://iom.nationalacademies.org/Reports/2011/Clinical-Practice-Guidelines-We-Can-Trust.aspx

2014 Evidence-Based Guidelines for the Management of High Blood Pressure in Adults: JNC 8

Paul A. James, MD1; Suzanne Oparil, MD2; Barry L. Carter, PharmD1; William C. Cushman, MD3; Cheryl Dennison-Himmelfarb, RN, ANP, PhD4; Joel Handler, MD5; Daniel T. Lackland, DrPH6; Michael L. LeFevre, MD, MSPH7; Thomas D. MacKenzie, MD, MSPH8; Olugbenga Ogedegbe, MD, MPH, MS9; Sidney C. Smith Jr, MD10; Laura P. Svetkey, MD, MHS11; Sandra J. Taler, MD12; Raymond R. Townsend, MD13; Jackson T. Wright Jr, MD, PhD14; Andrew S. Narva, MD15; Eduardo Ortiz, MD, MPH16,17

JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427.

Question for Audience

Who here has read or are familiar with the new JNC 8 guidelines?

A. Yes, I use them dailyB. Yes, I use them occasionallyC. Somewhat, I am not involved in HTN managementD. No, JNC what??

Why do we care?• About 70 million American adults (29%) have high blood

pressure—that’s 1 of every 3 adults.• Only about half (52%) of people with high blood pressure

have their condition under control.• Nearly 1 of 3 American adults has prehypertension—blood

pressure numbers that are higher than normal, but not yet in the high blood pressure range.

• High blood pressure costs the nation $46 billion each year. This total includes the cost of health care services, medications to treat high blood pressure, and missed days of work.

http://www.cdc.gov/bloodpressure/facts.htm

JNC 8

• Consists of 9 recommendations• Evidence review limited to random controlled trials (RCT)• Following 3 questions guided the evidence review:

1. In adults with hypertension, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes?

2. In adults with hypertension, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes?

3. In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes?

JNC 8 • Each recommendation is given a strength rating

Grade Strength of Recommendation

A Strong Recommendation

B Moderate Recommendation

C Weak Recommendation

D Recommendation against

E Expert Opinion

N No recommendation

Topic JNC 7 JNC 8Methodology Nonsystemic literature

review with range of study designs

Initial systemic review by methodologists restricted to RCT

Definitions Defined hypertension and prehypertension

Definitions of hypertension and prehypertension not addressed

Treatment Goals Separate goals for “uncomplicated” hypertension and for subsets with various comorbid conditions

Similar treatment goals for all hypertensive populations except when evidence review supports different goals

Lifestyle Recommendations Based on literature review and expert opinion

Endorsement of evidence-based Recommendations of the Lifestyle Work Group

Drug Therapy 5 classes considered for initial, but thiazide-type diuretics for most patients

4 classes and doses based on RCT evidence

Old vs. New

JNC 8: Recommendation 1

In the general population aged ≥ 60 years, initiate pharmacologic treatment to lower BP at SBP ≥ 150 mmHg or DBP ≥ 90 mmHg and treat to a goal SBP < 150 mmHg and goal DBP <90 mmHg.

Strong Recommendation: Grade A

JAMA. 2014;311(5):507-520.

JNC 8: Corollary Recommendation

In the general population aged ≥ 60 years, if pharmacologic treatment for high BP results in lower achieved SBP (eg, <140 mmHg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted

Expert Opinion: Grade E

JNC 8: Recommendation 2

In the general population < 60 years, initiate pharmacologic treatment to lower BP at DBP ≥ 90 mmHg and treat to a goal DBP < 90 mmHg.

Ages 30-59 years, Strong Recommendation: Grade AAges 18-29 years, Expert Opinion: Grade E

JAMA. 2014;311(5):507-520.

JNC 8: Recommendation 3

In the general population <60 years, initiate pharmacologic treatment to lower BP at SBP ≥ 140 mmHg and treat to a goal SBP <140 mmHg.

Expert Opinion: Grade E

JAMA. 2014;311(5):507-520.

JNC 8: Recommendation 4

In the population aged ≥ 18 years with CKD, initiate pharmacologic treatment to lower BP at SBP ≥ 140 mmHg or DBP ≥ 90 mmHg and treat to goal SBP <140mm Hg and DBP <90 mmHg.

Expert Opinion: Grade E

JAMA. 2014;311(5):507-520.

JNC 8: Recommendation 5

In the population aged ≥ 18 years with diabetes, initiate pharmacologic treatment to lower BP at SBP ≥ 140 mmHg or DBP ≥ 90 mmHg and treat to goal SBP < 140 and DBP < 90.

Expert Opinion: Grade E

JAMA. 2014;311(5):507-520.

JNC 8: Recommendation 6

In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB).

Moderate Recommendation: Grade B

*Note: No Beta Blockers

JAMA. 2014;311(5):507-520.

JNC 8: Recommendation 7

In the general black population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or CCB.

General black population, Moderate Recommendation: Grade BBlack patients with diabetes, Weak Recommendation: Grade C

JAMA. 2014;311(5):507-520.

JNC 8: Recommendation 8

In the population aged ≥ 18 years with CKD, initial (or add-on) antihypertensive treatment should include an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status.

Moderate recommendation: Grade B

JAMA. 2014;311(5):507-520.

JNC 8: Recommendation 9• The main objective of hypertension treatment is to attain and

maintain goal BP. • If goal BP is not reached within a month of treatment, increase

the dose of the initial drug or add a second drug from one of the classes in recommendation 6 (thiazide-type diuretic, CCB, ACEI, or ARB).

• If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list.

• May use antihypertensives from other classes if goal BP cannot be reached using recommended drug classes because of contraindication or need to use more than 3 drug classes to reach goal BP

• Do NOT use ACEI and ARB togetherJAMA. 2014;311(5):507-520.

JNC 8: Summary

For general population without DM or CKD:

Age ≥ 60 years:BP goal < 150/90 mmHg

Age <60 years:BP goal < 140/90 mmHg

JNC 8: Summary

For all ages with DM (no CKD):BP goal < 140/90 mmHg

For all ages with CKD (with or without DM):BP goal < 140/90 mmHg

JNC 8: Summary

For all ages and races with CKD

Initiate ACEI or ARB, alone or in combo with other drug class

JNC 8: Summary

For Black Population

Initiate thiazide-type diuretic or CCB, alone or in combo with other drug class

JNC 8: Summary

For Nonblack Population

Initiate thiazide-type diuretic or ACEI or ARB or CCB, alone or in combo

JNC 8: Treatment Algorithm

JNC 8: Treatment Algorithm

The controversy begins…

JNC 8 Controversy: BP Recommendation of <150/90 for 60+

Pro• Less aggressive

treatment of high BP• Less medication use in

elderly population (less drug interactions, adverse events, etc.)

Con• Possibility of increasing

goal in high risk population will increase CVD• Evidence to increase goal

insufficient• Could reverse reduction

in CVD rates over past decades

JNC 8 Controversy: BP Recommendation of <140/90 for DM

Pro• Less aggressive

treatment of high BP• Less medication use in

population with other comorbidities (less drug interactions, adverse events, etc.)

Con• Possibility of increasing

goal in high risk population will increase CVD• Based on expert opinion,

not RCT evidence

Patient Case: 65 yr old white male

PMH:DMHTNHLD

Pertinent Vitals:BP 138/75HR 74

Medications:Enalapril 10mg dailySimvastatin 40mg at bedtimeFish oil 1000mg twice dailyMetformin 500mg twice daily

Patient Case: 65 yr old male

What is the next step you would take to control patient’s hypertension?

A. Recommend increasing enalapril to 20mg dailyB. Recommend adding chlorthalidone 25mg dailyC. No change, patient at goalD. Both A and B

Patient Case: 52 yr old black female

PMH:HTN

Pertinent Vitals:BP 155/86

No medications

Patient Case: 52 yr old black female

What is the next step you would take to control patient’s hypertension?

A. Recommend starting lisinopril 10mg dailyB. Recommend starting metoprolol tartrate 25mg twice

dailyC. Recommend starting hydrochlorothiazide 25mg dailyD. Start lisinopril 10mg daily and losartan 25mg daily

Patient Case: 70 yr old white female

PMH:HTNHFCKD

Pertinent Vitals:BP 146/90

Medications:Amlodipine 10mg dailyMetoprolol succinate 100mg daily

Patient Case: 70 yr old white female

What is the next step you would take to control patient’s hypertension?

A. No change, patient at goalB. Recommend starting lisinopril 10mg dailyC. Recommend increasing metoprolol succinate doseD. Recommend starting spironolactone 25mg daily

Patient CasesPatients JNC 7 JNC 8

65 yo white male with DM, HTN, and HLD. Most recent BP 138/75. Currently on enalapril 10mg daily for HTN.

Goal BP < 130/80mmHgOptimize enalapril dose or add another drug (diuretic, ARB, BB, CCB)

Patient at goal.Continue current therapy.

52 yo black female recently diagnosed with HTN, BP 155/86. What therapy should be initiated?

Goal BP < 140/90mmHgFor Stage I HTN without compelling indications: start either thiazide-type diuretic, ACEI, ARB, BB, CCB, or combination.

Goal BP < 140/90mmHgFor black population, start thiazide-type diuretic or CCB.

70 yo white female with HTN, HF, and CKD. BP 146/90. Currently takes amlodipine 10mg daily and metoprolol succinate 100mg daily.

Goal BP < 130/80mmHgHF: Thiaz, BB, ACEI, ARB, Aldo antCKD: ACEI, ARB

Goal BP < 140/90For CKD, consider ACEI or ARB.

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in AdultsA report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Stone, Neil et al. “2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.” Circulation, 85. Web 13 Nov. 2013.

Old vs New

Old Guidelines• Treat to target LDL• Use of multiple drug

classes to achieve LDL goal • Monitor lipids to assess if

at goal

New Guidelines• Assess cardiovascular risk• Most benefit from statin

use• Instead of treating to LDL

target, more important to start statin dose to reduce CV risk

• Monitoring only for tolerability and adherence to therapy

ATP III- SummaryRisk Category LDL Goal LDL Level at Which

to Initiate Therapeutic Lifestyle Changes (TLC)

LDL Level at Which to Consider Drug Therapy

CHD or CHD Risk Equivalents* (10-year risk >20%)

< 100 mg/dL ≥ 100 mg/dL ≥ 130 mg/dL (100-129 mg/dL: drug optional)

2+ Risk Factors** and 10-year risk 10-20%

< 130 mg/dL ≥ 130 mg/dL ≥ 130 mg/dL

2+ Risk Factors ** and 10-year risk < 10%

< 130 mg/dL ≥ 130 mg/dL ≥ 160 mg/dL

0-1 Risk Factor** < 160 mg/dL ≥ 160 mg/dL ≥ 190 mg/dL (160-189 mg/dL: LDL-lowering drug optional

*CHD Risk Equivalents: DM, PAD, AAA, CAD**Risk Factors: Cigarette smoking, Hypertension (BP ≥ 140/90 or on antihypertensives), Low HDL (< 40 mg/dL), Family History of CHD (male first degree relative <55 years; female first degree relative <65 years), Age (men ≥ 45 years; women ≥ 55 years)

http://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf

2013 ACC/AHA Guidelines• Goals:• Prevent cardiovascular diseases• Improve the management of people who have these diseases

through professional education and research• Develop guidelines, standards, and policies that promote optimal

patient care and cardiovascular health

• Reviewed RCTs and systemic reviews and meta-analyses of RCTs with ASCVD outcomes

• Atherosclerotic cardiovascular disease (ASCVD) defined as:• Coronary heart disease (CHD)• Stroke• Peripheral arterial disease (PAD)

2013 ACC/AHA Guidelines

• Lifestyle as the Foundation for ASCVD Risk-Reduction Efforts• Lifestyle modification remains crucial (diet, exercise,

avoiding tobacco, and healthy weight)• Emphasize before and during treatment

2013 ACC/AHA Guidelines:4 Major Statin Benefit Groups

Clinical ASCVD*

LDL-C > 190 mg/dL

DM, 40-75 years, LDL 70-

190

LDL 70-189 and 10-year ASCVD risk

> 7.5%

*Clinical ASCVD is defined as acute coronary syndrome, history of MI, stable/unstable angina, coronary or other revascularization, stroke, TIA, or PAD.

Statin Therapy IntensityHigh-Intensity Statin

Moderate-Intensity Statin

Low-Intensity Statin

% LDL reduction

~50% ~30-50% <30%

Statin and dose

Atorvastatin 40-80mgRosuvastatin 20-40mg

Atorvastatin 10-20mgRosuvastatin 5-10mgSimvastatin 20-40mgPravastatin 40-80mgLovastatin 40mgFluvastatin XL 80mgFluvastatin 40mg BIDPitavastatin 2-4mg

Simvastatin 10mgPravastatin 10-20mgLovastatin 20mgFluvastatin 20-40mgPitavastatin 1mg

* Statins and doses in italics indicate doses have been approved by FDA but were not tested in the RCTs reviewed and boldface indicates evaluation in RCTs and demonstrated reduction in CV events.

ACC/AHA Recommendations

• Treatment Targets• No recommendation on LDL or HDL targets

• Secondary Prevention• High intensity statin for anyone age ≤ 75 years (A:

strong)• Moderate intensity statin if contraindicated (A:

strong)• For those >75 years, assess risk vs benefit of starting

high intensity or moderate intensity statin and of continuing statin therapy (E: Expert Opinion)

ACC/AHA Recommendations

• Primary Prevention: age ≥ 21 years with LDL ≥ 190 mg/dL• Evaluate for secondary causes of hyperlipidemia for

LDL >190 or TG >500 (B: Moderate)• High intensity statin regardless of 10-yr ASCVD risk,

or maximally tolerated statin (B: Moderate)• Intensify statin therapy to achieve a 50% LDL

reduction (E: Expert Opinion)• May consider adding non statin therapy for further

LDL reduction after maximum benefit from statin is achieved (E: Expert Opinion)

ACC/AHA Recommendation

• Primary Prevention: DM and LDL 70-189 mg/dL• Moderate intensity statin should be initiated or

continued for adults 40-75 years with DM (A: Strong)• High intensity statin reasonable for 10-yr ASCVD risk

≥ 7.5% (E: Expert Opinion)• Evaluate potential for ASCVD benefits for those with

DM < 40 years of age or >75 years (E: Expert Opinion)

ACC/AHA Recommendation

• Primary Prevention: without DM and LDL 70-189 mg/dL• Estimate 10-yr ASCVD risk to guide initiation of statin

therapy (E: Expert Opinion)• 10-yr ASCVD risk ≥ 7.5% treat with moderate-high intensity

statin (A: Strong)• 10-yr ASCVD risk 5-7.5% reasonable to offer moderate

intensity statin (C: Weak)• Before starting statin, engage in discussion with patient

regarding risk vs benefit (E: Expert Opinion)• For those not identified in statin benefit group, or risk is

uncertain, additional factors may be considered (E: Expert Opinion)

Additional factors to consider• For individuals who do not fit into 1 of the 4 benefit

groups, the factors listed below may be considered to make a treatment decision:• LDL-C ≥160 mg/dL or evidence of genetic hyperlipidemia• History of premature ASCVD with onset <55 yrs in first degree

male relative or <65 yrs in first degree female relative• High-sensitivity C-reactive protein ≥2 mg/L• Coronary artery calcium score ≥300 Agatson units or ≥75

percentile for age, sex, and ethnicity• Ankle-brachial index <0.9• Elevated lifetime risk of ASCVD

ACC/AHA Recommendation

• Heart Failure and Hemodialysis • No recommendation regarding initiation or

discontinuation of statins in patients with NYHA class II-IV ischemic systolic heart failure or maintenance hemodialysis (N: No Recommendation)

ASCVD 10 year risk• Clear net benefit of initiation of moderate-to-

high-intensity statin therapy with a risk of >7.5%. •When risk is between 5.0-7.5% there is still

net absolute benefit with moderate intensity statin – need to discuss with patient the risk and benefits of treatment.

• http://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx • IPhone App – ASCVD Risk Estimator• Gender• Age• Race• Total cholesterol• HDL-cholesterol• Systolic Blood Pressure• Treatment for Hypertension (Y/N)• Diabetes (Y/N)• Smoker (Y/N)

ASCVD 10 year risk calculator

Limitations of ASCVD Risk Calculator

• Not used if history of ASCVD or LDL-C >190 mg/dl• 10-year risk is only calculated for ages 40-79 years• Lifetime risk is only calculated for ages 20-59 years• Not accurate for races other than White or African

American• Total cholesterol between 130 and 320 mg/dL• HDL between 20 and 100 mg/dL• SBP between 90 and 200 mmHg

ACC/AHA Statin Initiation Recommendations

ACC/AHA Statin Initiation Recommendations, cont.

ACC/AHA Recommendation: Nonstatin Use• Before adding nonstatin, reemphasize adherence to

lifestyle changes and statin therapy• No data supporting routine use of nonstatin drugs +

statin to reduce ASCVD events• No RCTs assess ASCVD outcomes in statin-intolerant

patients• May consider in high risk individuals• ASCVD• LDL ≥ 190• DM aged 40-75 years

Monitoring Therapeutic Response and Adherence

ACC/AHA Summary

• No longer treat to a target number• Now target four focus groups:• With clinical ASCVD• LDL-C ≥190 mg/dL• Diabetes aged 40-75• Estimated 10-year ASCVD risk ≥ 7.5%

• Try to treat with maximum tolerated intensity of statin that is recommended• Goal of LDL-C reduction by ≥50% with high intensity

therapy or by 30-50% with moderate intensity therapy• Monitoring is done to assess response and adherence

And the controversy continues…

ACC/AHA 2013 Cholesterol Guidelines

Pros• Fairly clear steps of

identify risk group, assess need for statin and intensity• May help reduce under-

treatment• Less monitoring

necessary

Cons• What about patients who

can’t tolerate any statins?• Some prefer treat to

target• ASCVD calculator may

overestimate CVD risk• May lead to

overtreatment• May hurt adherence

without routine monitoring

Patient Case JR: 55 yr old female

PMH:DM HTNDepression

BP 146/84HR 82 bpm

Pertinent labs:LDL 134 HDL 51TG 253 TC 236

Medications:Metformin 500mg bidLisinopril 20mg dailyAmlodipine 10mg daily

Patient Case JR: 55 yr old female

What would be a reasonable next step to help reduce JR’s CVD risk?A. Recommend high intensity statinB. Recommend niacin 500mg twice dailyC. No change patient at goalD. Recommend low intensity statin

Patient Case JR: 55 yr old female

ASCVD 10 YR RISK

F-HAM10 YR RISK

ATP III: STATIN INDICATED

ACC/AHA: STATIN INDICATED

8.4% 5% LDL lowering therapy, may be statin

Yes

High intensity

Patient Case JR: 76 yr old female

PMH:DM HTNDepression

BP 146/84HR 82 bpm

Pertinent labs:LDL 134 HDL 51TG 253 TC 236

Medications:Metformin 500mg bidLisinopril 20mg dailyAmlodipine 10mg daily

Patient Case JR: 76 yr old female

What would be a reasonable next step to help reduce JR’s CVD risk?A. Recommend high intensity statinB. Recommend niacin 500mg twice dailyC. No change patient at goalD. Recommend low intensity statin

Patient Case JR: 76 yr old female

ASCVD 10 YR RISK

F-HAM10 YR RISK

ATP III: STATIN INDICATED

ACC/AHA: STATIN INDICATED

49% 17% LDL lowering therapy, may be statin

Maybe, evidence for >75 yo unclear

Summarize

“… recommendations are not a substitute for clinicaljudgment, and decisions about care must carefullyconsider and incorporate the clinical characteristics andcircumstances of each individual patient.” from JNC 8

• National guidelines help guide care with evidence-based practice• Must consider each individual patient and assess risk

vs benefit

Questions