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Changes in Guideline Trends and Applications in Practice: JNC 2013

George L. Bakris, MD, FAHA, FASN

Professor of Medicine

Director of the ASH Hypertension Center

The University of Chicago Medicine

Chicago, Illinois

JNC V

Optimal110120130140150160170180190200210220

JNC BP Classifications: SBP

JNC I. JAMA. 1977;237:255-261.JNC II. Arch Intern Med. 1980;140:1280-1285.JNC III. Arch Intern Med. 1984;144:1047-1057.

JNC IV. Arch Intern Med. 1988;148:1023-1038.JNC V. Arch Intern Med. 1993;153:154-183.JNC VI. Arch Intern Med. 1997;157:2413-2446.JNC 7. JAMA. 2003;289:2560-2572.

JNC I JNC II JNC III JNC IV JNC VI

Border- line

ISH

Stage 1 Stage 1

Stage 2

Stage 3

High-normal

High-normal

NormalNormal

Optimal

SBP(mm Hg)

Normal

Border- line

ISH

Stage 4

No recommendations for SBP in JNC I

or JNC II

JNC 7

Stage 1

Stage 2

Prehyper-tension

Normal

Stage 3

Stage 2

JNC BP Classifications: DBP

80859095

100105110115120125130

JNC I JNC II JNC III JNC IV JNC V JNC VI

Considertherapy

Hyper-tensive

Mild Mild MildStage 1 Stage 1

Moderate Moderate Moderate

Stage 2

Severe Severe SevereStage 3 Stage 3

Stage 2

Stage 4

High-normal

High-normal

High-normal

High-normal

Normal Normal Normal Normal

Optimal

DBP(mm Hg)

Optimal

JNC 7

Stage 1

Stage 2

Prehyper-tension

Normal

JNC I. JAMA. 1977;237:255-261.JNC II. Arch Intern Med. 1980;140:1280-1285.JNC III. Arch Intern Med. 1984;144:1047-1057.

JNC IV. Arch Intern Med. 1988;148:1023-1038.JNC V. Arch Intern Med. 1993;153:154-183.JNC VI. Arch Intern Med. 1997;157:2413-2446.JNC 7. JAMA. 2003;289:2560-2572.

JNC 8 is not just JNC 7 “Retooled” or “Repainted”, but Imploded and Reconstructed

National High Blood Pressure Education Program

Coordinating CommitteeAmerican Academy of Family PhysiciansAmerican Academy of NeurologyAmerican Academy of OphthalmologyAmerican Academy of Physician AssistantsAmerican Association of Occupational Health NursesAmerican College of CardiologyAmerican College of Chest PhysiciansAmerican College of Occupational and Environmental MedicineAmerican College of Physicians

—American Society of Internal MedicineAmerican College of Preventive MedicineAmerican Dental AssociationAmerican Diabetes AssociationAmerican Dietetic AssociationAmerican Heart AssociationAmerican Hospital AssociationAmerican Medical AssociationAmerican Nurses AssociationAmerican Optometric AssociationAmerican Osteopathic AssociationAmerican Pharmaceutical AssociationAmerican Podiatric Medical AssociationAmerican Public Health AssociationAmerican Red Cross

American Society of Health-System PharmacistsAmerican Society of HypertensionAmerican Society of NephrologyAssociation of Black CardiologistsCitizens for Public Action on High Blood Pressure and Cholesterol, Inc.Hypertension Education Foundation, Inc.International Society on Hypertension in BlacksNational Black Nurses Association, Inc.National Hypertension Association, Inc.National Kidney Foundation, Inc.National Medical AssociationNational Optometric AssociationNational Stroke AssociationNHLBI Ad Hoc Committee on Minority PopulationsSociety for Nutrition EducationThe Society of Geriatric CardiologyFederal Agencies:Agency for Healthcare Research and QualityCenters for Medicare & Medicaid Services Department of Veterans AffairsHealth Resources and Services AdministrationNational Center for Health Statistics National Heart, Lung, and Blood InstituteNational Institute of Diabetes and Digestive and Kidney Diseases

JNC 7 Algorithm for Treatment of Hypertension

Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)

as needed.

With Compelling Indications

Lifestyle Modifications

Stage 2 Hypertension(SBP >160 or DBP >100 mmHg)

2-drug combination for most (usually thiazide-type diuretic and

ACEI, or ARB, or BB, or CCB)

Stage 1 Hypertension(SBP 140–159 or DBP 90–99 mmHg)

Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB,

or combination.

Without Compelling Indications

Not at Goal Blood Pressure

Optimize dosages or add additional drugs until goal blood pressure is achieved.

Consider consultation with hypertension specialist.

JNC 7. JAMA. 2003;289:2560-2572.

JNC 7 Compelling Indications

BB, beta blocker; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker;CCB, calcium channel blocker; AA, aldosterone antagonist; HF, Heart Failure;MI, myocardial infarction; CAD, coronary artery disease; DM, diabetes mellitus JNC 7. JAMA. 2003;289:2560-2572.

Heart Failure

Post MI

CAD risk

Diabetes Mellitus

Renal disease

Recurrent strokeprevention

BB

ACEI

ARB

CCB

AADiuretic

ACC/AHA Clinical Practice Guidelines Hierarchical Grading System

ACC/AHA Clinical Practice Guidelines Hierarchical Grading System

Class I(“Useful & Effective”)(Benefit >>>

risk)(Highly

recommended)

Class II (“Conflicting Evidence”)

Class III(“Not useful/

effective, may be harmful”)

(No benefit/Harm)(Not

recommended)

IIa(Benefit >>risk)

(Reasonably recommended)

IIb(Benefit ?

risk)(May be

considered)

Level A(Multiple

randomized clinical trials)

Level B(Single

randomized trial or

nonrandomized studies

Level C(Consensus

opinion, case studies, or

standard of care)

Scientific Evidence Underlying the ACC/AHA Clinical Practice Guidelines

Among ACC/AHA guidelines updated by Sept. 2008:48% increase (1330 to 1973) in # of recommendations occurred, the largest # being Class II (conflicting evidence)

Of 16 current guidelines with level of evidence recs:—12% (314/2711) are Level A (multiple RCTs) —46% (1246/2711) are Level C (expert opinion, … no

RCTs)

Only 9% (245/2711) are Class I and Level A

Increased Resources($) are needed to fund trials supporting guideline development …

Tricoci, et al. JAMA. 2009; 301: 831 - 841

Update clinical recommendations on BP, cholesterol, and obesity– Use systematic evidence review process – Use evidence & recommendations grading– Standardize & coordinate approaches– Develop consistent recommendations for lifestyle & risk

assessment Create integrated CV risk reduction recommendations

– Individual risk factor guidelines + lifestyle and risk assessment + additional CVD risk reduction approaches

Develop comprehensive approach to implementation– Write guidelines clearly so they are implementable – Address patient, clinician, and systems levels– Develop and disseminate materials & tools– Develop an evidence-based implementation plan– Establish a National Program to Reduce Cardiovascular Risk

NHLBI Cardiovascular Prevention Guidelines New Directions

NHLBI Systematic Review and Guideline Development Process

Literature Searched;Eligible Studies

Identified

Studies Quality Rated;Data Abstracted

Evidence TablesDeveloped;

Body of Evidence Summarized

External Reviewof Recommendation

Drafts; Revisedas Needed

Guidelines Disseminated &

Implemented

Graded Evidence Statements &

RecommendationsDeveloped

Expert PanelSelected

Topic Area Identified

Critical Questions &Study EligibilityCriteria Identified

NHLBI Evidence Quality Rating and Recommendation Strength

Evidence Quality• High

– Well-designed and conducted RCTs

• Moderate – RCTs with minor limitations– Well-conducted

observational studies

• Low– RCTs with major limitations– Observational studies with

major limitations

Recommendation Strength

A – Strong

B – Moderate

C – Weak

D – Against

E – Expert Opinion

N – No Recommendation

JNC 2013:Initial Question Areas Being Addressed• Among adults, does treatment with antihypertensive

pharmacological therapy to a specific BP goal lead to improvements in health outcomes? (how low should you go)

• Among adults with hypertension, does initiating antihypertensive pharmacological therapy at specific BP thresholds improve health outcomes? (when to initiate drug treatment)

• In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? (How do we get there?)

Inclusion/Exclusion Criteria for Studies

• Randomized Controlled trials

• 1966-present

• Minimum one year follow-up

• Studies with samples size <100 excluded

JNC 2013:Initial Question Areas Being Addressed

• (how low should you go) N=56• (when to initiate drug treatment) N=26• (How do we get there?) N=66

BP Level-How Low to go• General population

• Elderly

• Kidney Disease

2013 BP Guideline Goal<140/90 mmHg

KDIGO/KDOQI

NICE

Latin Am. Consortium for Diabetes Management

Am Diabetes Assoc.- <140/80 mmHg

ONTARGET: Relationships Between Outcome Risks and In-Trial BP

• J-shaped curve (nadir ≈ 130 mm Hg) for primary outcomea, MI, CV mortality (not stroke)• Continual risk increase (no J-shaped curve) for stroke• Suggests increased risk of events in patients with extensive vascular disease when BP is

decreased below a critical level

Adj

uste

d 4.

5-y

Ris

k of

Eve

nts

(%)

In-treatment SBP, deciles (mmHg)

Sleight P, et al. J Hypertens. 2009;27:1360-1369.

HR

, 95%

Confidence Interval

Primary study outcome

aComposite of cardiovascular death, MI, stroke, or hospitalization for congestive heart failure (CHF).

112 121 126 130 133 136 140 144 149 1610

5

10

15

20

25

30

0

0.5

1

1.5

2

2.5

3

Weber M et.al. submitted Am J Med.

CV outcomes from the ACCOMPLISH trial

16.3

8.69.6

5.1

9.9

5.3

0

5

10

15

20

Primary Endpoint

Death/MI/stroke/revascularization

All-cause mortality

Out

com

e (%

)

SBP > 140 mmHg

SBP 130–140 mmHgSBP < 130 mmHg

OUTCOMES: (MI, stroke, revascularization, all-cause mortality)

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly

A Report of the American College of Cardiology Foundation Task Force on Expert ConsensusDocuments

Aronow W et.al. JACC 2011;57:2037-2114

Percentage of People in Outcome Trials of the Elderly Taking > 2 Antihypertensive Medication

STONE (147 mmHg)

MRC‐elderly (153 mmHg)

EWPHE (151 mmHg)

Australian HTN (142 mmHg)

INVEST (136 mm Hg)

ALLHAT (138 mm Hg)

ACCOMPLISH (131 mmHg)

STOP‐2 (151 mmHg)

SYST‐China (not reported)

Syst‐Eur (151 mmHg)

HYVET (138 mmHg)

CONVINCE (136 mmHg)

SHEP (146 mmHg)

LIFE (143 mmHg)

Trial/SBP Achieved

% patientsN=14 studies;43% >2 drugs

ACC Guidelines in Elderly 2011- JACC 2011

Major “Take Home” Message of Elderly Guidelines-Management1) Original goal by evidence <150/80 mmHg, (2B)

The general recommended BP goal after public input consensus in uncomplicated hypertension (age 65-79) was <140/90 mmHg but 140-145 is acceptable. (2C)

• Initial antihypertensive drugs should be started at the lowest dose and gradually increased, depending on BP response, to the maximum tolerated dose.

• No specific recommended for octogenarians.

Aronow W et.al. JACC 2011;57:2037-2114

BP level and CKD• <140/90 mmHg

24

Composite Ranking for Relative Risks by glomerular filtration rate (GFR) and Albuminuria (Kidney Disease: Improving Global Outcomes (KDIGO) 2009

25

Levey AS et.al. Kidney Int 2010; doi: 10.1038/ki.2010.483

Risk of coronary events in people with CKD compared with diabetes: a population‐level cohort study

Tonelli M et.al. The Lancet 2012;380:807‐812; Polonsky& Bakris Lancet 2012;380:783‐785

NHANES 2003‐200648 month FUN=1,268,029

Associations of CKD with mortality and end‐stage renal disease in individuals with and without hypertension: a meta‐analysis

Mahmoodi K et.al. Lancet –Sept 24 2012 Ref. pt.= eGFR 95 without hypertension

Interaction

Steno-2: Intensive Multiple Risk Factor Management

Cardiovascular Events

Years of Follow-upNo. at RiskIntensive therapy 80 72 65 61 56 50 47 31Conventional therapy 80 70 60 46 38 29 25 14

Intensive Therapy

Conventional Therapy

0 1 2 3 4 5 6 7 8 9 10 11 12 13Cum

ulat

ive

Inci

denc

e of

Any

C

ardi

ovas

cula

r Eve

nt (%

)

010

20

30

40

50

60

70

80

HR=0.41; p< 0.001Absolute RR= 29%HR for Total Mortality: 0.54; p=0.02Absolute RR= 20%

Gaede P, et al. NEJM. 2008;358:580-591.

Changes in Selected Risk Factors during the Interventional Study and Follow-up Period (13.3 years).

Gæde P et al. N Engl J Med 2008;358:580-591.

WhatistheGoalBPandInitialTherapyinKidneyDiseaseorDiabetestoReduceCVRisk?

* Indicates use with diuretic

Group Goal BP (mmHg) Initial Therapy

ADA(2012) <130/80 ACEInhibitor/ARB*KDOQI(NKF)(2007) <130/80 ACEInhibitor/ARBESH(2007+2009) <130/80 ACEInhibitor/ARB*KDOQI(NKF)(2004) <130/80 ACEInhibitor/ARB*

JNC7(2003) <130/80 ACEInhibitor/ARB*Am.DiabetesAssoc(2003) <130/80 ACEInhibitor/ARB*CanadianHTNSoc.(2002) <130/80 ACEInhibitor/ARB*

Am.DiabetesAssoc(2002) <130/80 ACEInhibitor/ARB*

Natl.KidneyFoundation(2000) <130/80 ACEInhibitor*

BritishHTNSoc.(1999) <140/80 ACEInhibitor

WHO/ISH(1999) <130/85 ACEInhibitor

JNCVI(1997) <130/85 ACEInhibitor 30

SBP=systolic blood pressure. *Target blood pressure control groups in ACCORD defined as <120 mm Hg (intensive) and <140 mm Hg (standard).Copley JB, Rosario R. Dis Mon. 2005;51:548-614.The ACCORD Study Group. N Engl J Med. 2010 Mar 14. [Epub ahead of print]

ALLHAT 138HOT 138ACCOMPLISH 132ACCORD (intensive)* 119ACCORD (standard)* 133INVEST 133IDNT 138RENAAL 141ABCD 132UKPDS 144

MDRD 132AASK 128

Multiple Medications Are Required to Achieve BP Control in Clinical Trials

Hypertension

Diabetes

Kidneydisease

No. of BP medications1 2 3 4

SBP achieved (mm Hg)Trial

Blood Pressure Targets in Chronic Kidney Disease: Proteinuria as an Effect Modifier

• 3 RCTs (8 reports) with a total of 2272 participants– MDRD (Modification of Diet in Renal Disease)

Study – AASK (African American Study of Kidney Disease

and Hypertension) Trial – REIN-2 (Ramipril Efficacy in Nephropathy 2) trial

• 2- to 4-year trial follow-up

Upadhyay A, et al. Annals Intern Med 3/2011

Peralta, C. A. et al. Arch Intern Med 2012;172:41-47.

Rates of end-stage renal disease per 1000 person-years

16,000+ personsMean follow-up 2.8 yrs

Guide to KDIGO Grades

GRADE PATIENTS CLINICIANS POLICY

1We

Recommend

Most people in yoursituation would want the recommended course of action and only a few would not.

Most patients should receive therecommended course of action.

The recommendation can be evaluated as a candidate for developing a policy or a performancemeasure.

2We Suggest

The majority of people in your situation would want the recommended course of action, but many would not.

Different choices will be appropriate for different patients.Each patient needshelp to arrive at amanagement decision consistent with her or his values and preferences.

There is a need forsubstantial debate and involvement of stakeholders.

Implications

Grade Quality ofEvidence

Meaning

A High We are confident that the true effect lies close to that of the estimate of the

effect.

B Moderate The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

C Low The true effect may be substantially different from the estimate of the effect.

D Very Low The estimate of effect is very uncertain and often will be far from the truth.

Guide to KDIGO Grades

KDIGO BP Guidelines 2012-BLOOD PRESSURE MANAGEMENT IN CKD WITHOUT DIABETES

• We recommend that non‐diabetic adults with CKD and urine albumin excretion <30 mg/24 h (or equivalent*) whose office BP is consistently >140 mm Hg during systole or >90 mm Hg during diastole be treated with BP‐lowering drugs to maintain a BP that is consistently ≤140 mm Hg systolic and ≤90 mm Hg diastolic.

• GRADE 1B• We suggest that non‐diabetic adults with CKD and with urine

albumin excretion of 30 to 300 mg/24 h (or equivalent*) whose office BP is consistently >130 mm Hg during systole or >80 mm Hg during diastole be treated with BP‐lowering drugs to maintain a BP that is consistently ≤130 mm Hg systolic and ≤80 mm Hg diastolic.

• GRADE 2DKidney Int Suppl Dec 2012

KDIGO BP Guidelines 2012-BLOOD PRESSURE MANAGEMENT IN CKD WITHOUT DIABETES

• We suggest that non‐diabetic adults with CKD and urine albumin excretion>300 mg/24 h (or equivalent*) whose office BP is consistently >130 mm Hg during systole or >80 mm Hg during diastole be treated with BP‐lowering drugs to maintain a BP that is consistently ≤130 mmHg systolic and ≤80 mm Hg diastolic.

• GRADE 2C

• We suggest that an ARB or ACE‐I be used as first‐line therapy in non‐diabetic adults with CKD and with urine albumin excretion of 30 to 300 mg/24 h (or equivalent*) in whom treatment with BP‐lowering drugs is indicated.

• GRADE 2DKidney Int Suppl Dec 2012

Initial Combinations of Medications*

Thiazide-Like Diuretics

ACE inhibitorsor

ARBs

Calciumantagonists

* Compelling indications may modify this.

-blockers should be included in the regimen if there is a compelling indication for a -blocker

Conclusion (my opinion)• The BP for everyone will be <140/90 mmHg

• BP for those >60- <150/90 mmHg

• Combinations of RAS blockers with thiazide diuretics or RAS blockers and dihydropyridine CCBs are acceptable first line combos to get BP to goal, if >20/10 mmHg above goal