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 BP Classifications: SBP

220 210 200 190 180 170 SBP (mm Hg) 160 150 140 130 120 110
Stage 4

Stage 3 ISH ISH Stage 2 Border - line No recommendations for SBP in JNC I or JNC II Border - line

Stage 3

Stage 2

Stage 2

Stage 1 Highnormal

Stage 1 Highnormal Normal

Stage 1 Prehypertension

Normal Normal Optimal

Optimal

Normal

JNC I

JNC II

JNC III

JNC IV

JNC V

JNC VI

JNC 7

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 BP Classifications: DBP

130 125 120 115 110 DBP (mm Hg) 105 100 95 90 85 80
Stage 4 Severe Hypertensive Moderate Severe Moderate Severe Moderate Stage 2 Consider therapy Mild Mild Mild Stage 1 Highnormal Normal Highnormal Normal Highnormal Normal Optimal Stage 1 Highnormal Normal Optimal Stage 1 Stage 2 Stage 2

Stage 3

Stage 3

Prehypertension Normal

JNC I

JNC II

JNC III

JNC IV JNC V

JNC VI

JNC 7

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 Committee

American Academy of Family Physicians American Academy of Neurology American Academy of Ophthalmology American Academy of Physician Assistants American Association of Occupational Health Nurses American College of Cardiology American College of Chest Physicians American College of Occupational and Environmental Medicine American College of Physicians American Society of Internal Medicine American College of Preventive Medicine American Dental Association American Diabetes Association American Dietetic Association American Heart Association American Hospital Association American Medical Association American Nurses Association American Optometric Association American Osteopathic Association American Pharmaceutical Association American Podiatric Medical Association American Public Health Association American Red Cross American Society of Health-System Pharmacists American Society of Hypertension American Society of Nephrology Association of Black Cardiologists Citizens for Public Action on High Blood Pressure and Cholesterol, Inc. Hypertension Education Foundation, Inc. International Society on Hypertension in Blacks National Black Nurses Association, Inc. National Hypertension Association, Inc. National Kidney Foundation, Inc. National Medical Association National Optometric Association National Stroke Association NHLBI Ad Hoc Committee on Minority Populations Society for Nutrition Education The Society of Geriatric Cardiology Federal Agencies: Agency for Healthcare Research and Quality Centers for Medicare & Medicaid Services Department of Veterans Affairs Health Resources and Services Administration National Center for Health Statistics National Heart, Lung, and Blood Institute National Institute of Diabetes and Digestive and Kidney Diseases

National High Blood Pressure Education Program Coordinating Committee

American Academy of Family Physicians American Academy of Neurology American Academy of Ophthalmology American Academy of Physician Assistants American Association of Occupational Health Nurses American College of Cardiology American College of Chest Physicians American College of Occupational and Environmental Medicine American College of Physicians American Society of Internal Medicine American College of Preventive Medicine American Dental Association American Diabetes Association American Dietetic Association American Heart Association American Hospital Association American Medical Association American Nurses Association American Optometric Association American Osteopathic Association American Pharmaceutical Association American Podiatric Medical Association American Public Health Association American Red Cross American Society of Health-System Pharmacists American Society of Hypertension American Society of Nephrology Association of Black Cardiologists Citizens for Public Action on High Blood Pressure and Cholesterol, Inc. Hypertension Education Foundation, Inc. International Society on Hypertension in Blacks National Black Nurses Association, Inc. National Hypertension Association, Inc. National Kidney Foundation, Inc. National Medical Association National Optometric Association National Stroke Association NHLBI Ad Hoc Committee on Minority Populations Society for Nutrition Education The Society of Geriatric Cardiology Federal Agencies: Agency for Healthcare Research and Quality Centers for Medicare & Medicaid Services Department of Veterans Affairs Health Resources and Services Administration National Center for Health Statistics National Heart, Lung, and Blood Institute National Institute of Diabetes and Digestive and Kidney Diseases

JNC 7 Algorithm for Treatment of Hypertension

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

Initial Drug Choices

Without Compelling Indications

With Compelling Indications

Stage 1 Hypertension
(SBP 140159 or DBP 9099 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination.

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)

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.

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

Diuretic Heart Failure Post MI CAD risk Diabetes Mellitus Renal disease Recurrent stroke prevention BB ACEI ARB CCB AA

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.

ACC/AHA Clinical Practice Guidelines

Hierarchical Grading System
Class I (Useful & Effective)
(Benefit >>> risk)
(Highly recommended)

Class II (Conflicting Evidence)

IIa (Benefit >>risk) (Reasonably recommended) IIb (Benefit ? risk) (May be considered)

Class III (Not useful/ effective, may be harmful)

(No benefit/Harm) (Not recommended)

Level A
(Multiple randomized clinical trials)

Level B
(Single randomized trial or nonrandomized studies

Level C
(Consensus opinion, case studies, or standard of care)

 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

Scientific Evidence Underlying the ACC/AHA Clinical Practice Guidelines

NHLBI Cardiovascular Prevention Guidelines New Directions

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 Systematic Review and Guideline Development Process

Topic Area Identified Evidence Tables Developed; Body of Evidence Summarized Graded Evidence Statements & Recommendations Developed

Expert Panel Selected

Studies Quality Rated; Data Abstracted

External Review of Recommendation Drafts; Revised as Needed

Critical Questions &Study Eligibility Criteria Identified

Literature Searched; Eligible Studies Identified

Guidelines Disseminated & Implemented

NHLBI Evidence Quality Rating and Recommendation Strength

Evidence Quality Recommendation Strength

High
Well-designed and conducted RCTs

A Strong B Moderate C Weak

Moderate

RCTs with minor limitations D Against Well-conducted observational studies

E Expert Opinion

Low

RCTs with major limitations N No Recommendation Observational studies with major limitations

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

30

Primary study outcome Adjusted 4.5-y Risk of Events (%)

25 20 15 10 5 0 112 121 126 130 133 136 140 144 149 161

3 2.5 2 1.5 1 0.5 0

HR, 95% Confidence Interval

In-treatment SBP, deciles (mmHg)

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

aComposite

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

CV outcomes from the ACCOMPLISH trial

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

20
16.3

SBP > 140 mmHg SBP 130140 mmHg SBP < 130 mmHg
9.9 8.6 5.1 5.3

Outcome (%)

15
9.6

10

Primary Endpoint Death/MI/ stroke/revascularization

All-cause mortality

Weber M et.al. submitted Am J Med.

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

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

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

Percentage of People in Outcome Trials of the Elderly Taking > 2 Antihypertensive Medication
Trial/SBP Achieved
STONE MRCelderly EWPHE INVEST ALLHAT ACCOMPLISH STOP2 SystEur HYVET CONVINCE SHEP LIFE (147 mmHg) (153 mmHg) (151 mmHg) (136 mm Hg) (138 mm Hg) (131 mmHg) (151 mmHg) (151 mmHg) (138 mmHg) (136 mmHg) (146 mmHg) (143 mmHg)

Australian HTN (142 mmHg)

SYSTChina (not reported)

N=14 studies;43% >2 drugs ACC Guidelines in Elderly 2011- JACC 2011

%patients

Major Take Home Message of Elderly Guidelines-Management

1) 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

24

BP level and CKD

<140/90 mmHg

25

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

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

RiskofcoronaryeventsinpeoplewithCKDcompared withdiabetes:apopulationlevelcohortstudy
NHANES20032006 48monthFU N=1,268,029

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

AssociationsofCKDwithmortalityandendstagerenaldisease inindividualswithandwithouthypertension:ametaanalysis

Interaction

Mahmoodi Ket.al.LancetSept242012

Ref.pt.=eGFR95withouthypertension

Steno-2: Intensive Multiple Risk Factor Management

Cardiovascular Events

Cumulative Incidence of Any Cardiovascular Event (%)

8 0 7 0 6 0 5 0 4 0 3 0 2 0 1 0 0
0 1 2 3 4 5 6

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

Intensive Therapy
7 8 9 10 11 12 13

Years of Follow-up
No. at Risk Intensive therapy Conventional therapy 80 80 72 70 65 60 61 46 56 38 50 29 47 31 25 14

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.

What is the Goal BP and Initial Therapy in Kidney Disease or Diabetes to Reduce CV Risk?
Group
ADA (2012) KDOQI (NKF) (2007) ESH (2007+ 2009) KDOQI (NKF) (2004) JNC 7 (2003) Am. Diabetes Assoc (2003) Canadian HTN Soc. (2002) Am. Diabetes Assoc (2002) Natl. Kidney Foundation (2000) British HTN Soc. (1999) WHO/ISH (1999)
* IndicatesJNC VI (1997) use with diuretic

Goal BP (mmHg)
<130/80 <130/80 <130/80 <130/80 <130/80 <130/80 <130/80 <130/80 <130/80 <140/80 <130/85 <130/85

Initial Therapy
ACE Inhibitor/ARB* ACE Inhibitor/ARB ACE Inhibitor/ARB* ACE Inhibitor/ARB* ACE Inhibitor/ARB* ACE Inhibitor/ARB* ACE Inhibitor/ARB* ACE Inhibitor/ARB* ACE Inhibitor* ACE Inhibitor ACE Inhibitor ACE Inhibitor
30

Multiple Medications Are Required to Achieve BP Control in Clinical Trials

Trial ALLHAT Hypertension HOT ACCOMPLISH ACCORD (intensive)* ACCORD (standard)* INVEST Diabetes IDNT RENAAL ABCD UKPDS Kidney disease MDRD AASK SBP achieved (mm Hg) 138 138 132 119 133 133 138 141 132 144 132 128 1 2 3 4

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]

No. of BP medications

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

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

16,000+ persons Mean follow-up 2.8 yrs

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

GuidetoKDIGOGrades
Implications
GRADE
1 We Recommend

PATIENTS
Mostpeopleinyour situationwouldwantthe recommendedcourseof actionandonlyafew wouldnot.

CLINICIANS
Mostpatients shouldreceivethe recommended courseofaction.

POLICY
The recommendation canbeevaluatedas acandidatefor developingapolicy oraperformance measure.

2 WeSuggest

Themajorityofpeoplein yoursituationwould wanttherecommended courseofaction,but manywouldnot.

Differentchoiceswill beappropriatefor differentpatients. Eachpatientneeds helptoarriveata management decisionconsistent withherorhisvalues andpreferences.

Thereisaneedfor substantialdebate andinvolvement ofstakeholders.

GuidetoKDIGOGrades
Grade
A

Qualityof Evidence
High

Meaning
Weareconfidentthatthetrueeffectlies closetothatoftheestimateofthe effect. Thetrueeffectislikelytobeclosetothe estimateoftheeffect,butthereisa possibilitythatitissubstantially different. Thetrueeffectmaybesubstantially differentfromtheestimateoftheeffect. Theestimateofeffectisveryuncertain andoftenwillbefarfromthetruth.

Moderate

C D

Low VeryLow

KDIGO BP Guidelines 2012-BLOODPRESSURE MANAGEMENTINCKDWITHOUTDIABETES

WerecommendthatnondiabeticadultswithCKDandurine albuminexcretion<30mg/24h(orequivalent*)whoseofficeBP isconsistently>140mmHgduringsystoleor>90mmHgduring diastolebetreatedwithBPloweringdrugstomaintainaBPthat isconsistently140mmHgsystolicand90mmHgdiastolic. GRADE1B WesuggestthatnondiabeticadultswithCKDandwithurine albuminexcretionof30to300mg/24h(orequivalent*)whose officeBPisconsistently>130mmHgduringsystoleor>80mmHg duringdiastolebetreatedwithBPloweringdrugstomaintaina BPthatisconsistently130mmHgsystolicand80mmHg diastolic. GRADE2D
Kidney Int Suppl Dec 2012

KDIGO BP Guidelines 2012-BLOODPRESSURE MANAGEMENTINCKDWITHOUTDIABETES

WesuggestthatnondiabeticadultswithCKDandurine albuminexcretion>300mg/24h(orequivalent*)whoseoffice BPisconsistently>130mmHgduringsystoleor>80mmHg duringdiastolebetreatedwithBPloweringdrugstomaintaina BPthatisconsistently130mmHgsystolicand80mmHg diastolic. GRADE2C WesuggestthatanARBorACEIbeusedasfirstlinetherapyin nondiabeticadultswithCKDandwithurinealbuminexcretion of30to300mg/24h(orequivalent*)inwhomtreatmentwith BPloweringdrugsisindicated. GRADE2D
Kidney Int Suppl Dec 2012

Initial Combinations of Medications*

Thiazide-Like Diuretics

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

Calcium antagonists
* Compelling indications may modify this.

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