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

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 (100 mmHg)

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

ACEI, or ARB, or BB, or CCB)

Stage 1 Hypertension(SBP 140159 or DBP 9099 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

9

9

9

9

9

9

9

BB

9

9

9

9

9

ACEI

9

9

9

ARB

9

9

CCB

9

9

AADiuretic

9 9

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

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

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

Ad j

u st e

d 4 .

5 -y

Ri s

k o f

Ev e

n ts

( %)

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

Ou t

c om

e ( %

)

SBP > 140 mmHg

SBP 130140 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)

MRCelderly (153 mmHg)

EWPHE (151 mmHg)

Australian HTN (142 mmHg)

INVEST (136 mm Hg)

ALLHAT (138 mm Hg)

ACCOMPLISH (131 mmHg)

STOP2 (151 mmHg)

SYSTChina (not reported)

SystEur (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

BP level and CKD

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

RiskofcoronaryeventsinpeoplewithCKDcomparedwithdiabetes:apopulationlevelcohortstudy

Tonelli Met.al.TheLancet2012;380:807812;Polonsky&BakrisLancet2012;380:783785

NHANES2003200648monthFUN=1,268,029

AssociationsofCKDwithmortalityandendstagerenaldiseaseinindividualswithandwithouthypertension:ametaanalysis

Mahmoodi Ket.al.LancetSept242012 Ref.pt.=eGFR95withouthypertension

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 13Cu m

u la t

i ve

I nc i

d en c

e o f

An y

C

a rd i

o va s

c ul a

r Ev e

n t ( %

)

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).

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

WhatistheGoalBPandInitialTherapyinKidneyDiseaseorDiabetestoReduceCVRisk?

* Indicates use with diuretic

Group Goal BP (mmHg) Initial Therapy

30

SBP=systolic blood pressure. *Target blood pressure control groups in ACCORD defined as

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

GuidetoKDIGOGrades

GRADE PATIENTS CLINICIANS POLICY

1We

Recommend

Mostpeopleinyoursituationwouldwanttherecommendedcourseofactionandonlyafewwouldnot.

Mostpatientsshouldreceivetherecommendedcourseofaction.

Therecommendationcanbeevaluatedasacandidatefordevelopingapolicyoraperformancemeasure.

2WeSuggest

Themajorityofpeopleinyoursituationwouldwanttherecommendedcourseofaction,butmanywouldnot.

Differentchoiceswillbeappropriatefordifferentpatients.Eachpatientneedshelptoarriveatamanagementdecisionconsistentwithherorhisvaluesandpreferences.

Thereisaneedforsubstantialdebateandinvolvementofstakeholders.

Implications

Grade QualityofEvidence

Meaning

A High Weareconfidentthatthetrueeffectliesclosetothatoftheestimateofthe

effect.

B Moderate Thetrueeffectislikelytobeclosetotheestimateoftheeffect,butthereisapossibilitythatitissubstantiallydifferent.

C Low Thetrueeffectmaybesubstantiallydifferentfromtheestimateoftheeffect.

D VeryLow Theestimateofeffectisveryuncertainandoftenwillbefarfromthetruth.

GuidetoKDIGOGrades

KDIGO BP Guidelines 2012-BLOODPRESSUREMANAGEMENTINCKDWITHOUTDIABETES

WerecommendthatnondiabeticadultswithCKDandurinealbuminexcretion140mmHgduringsystoleor>90mmHgduringdiastolebetreatedwithBPloweringdrugstomaintainaBPthatisconsistently140mmHgsystolicand90mmHgdiastolic.

GRADE1B WesuggestthatnondiabeticadultswithCKDandwithurine

albuminexcretionof30to300mg/24h(orequivalent*)whoseofficeBPisconsistently>130mmHgduringsystoleor>80mmHgduringdiastolebetreatedwithBPloweringdrugstomaintainaBPthatisconsistently130mmHgsystolicand80mmHgdiastolic.

GRADE2DKidney Int Suppl Dec 2012

KDIGO BP Guidelines 2012-BLOODPRESSUREMANAGEMENTINCKDWITHOUTDIABETES

WesuggestthatnondiabeticadultswithCKDandurinealbuminexcretion>300mg/24h(orequivalent*)whoseofficeBPisconsistently>130mmHgduringsystoleor>80mmHgduringdiastolebetreatedwithBPloweringdrugstomaintainaBPthatisconsistently130mmHgsystolicand80mmHgdiastolic.

GRADE2C

WesuggestthatanARBorACEIbeusedasfirstlinetherapyinnondiabeticadultswithCKDandwithurinealbuminexcretionof30to300mg/24h(orequivalent*)inwhomtreatmentwithBPloweringdrugsisindicated.

GRADE2DKidney Int Suppl Dec 2012

Initial Combinations of Medications*

Thiazide-Like Diuretics

ACE inhibitorsor

ARBs

Calciumantagonists

* Compelling indications may modify this.

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

Conclusion (my opinion) The BP for everyone will be 60- 20/10 mmHg above goal