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
J NC V
Optimal
110
120
130
140
150
160
170
180
190
200
210
220
J NC BP Classifications: SBP
J NC I. JAMA. 1977;237:255-261.
J NC II. Arch Intern Med. 1980;140:1280-1285.
J NC III. Arch Intern Med. 1984;144:1047-1057.
J NC IV. Arch Intern Med. 1988;148:1023-1038.
J NC V. Arch Intern Med. 1993;153:154-183.
J NC VI. Arch Intern Med. 1997;157:2413-2446.
J NC 7. JAMA. 2003;289:2560-2572.
J NC I J NC II J NC III J NC IV J NC VI
Border
- line
ISH
Stage 1 Stage 1
Stage 2
Stage 3
High-
normal
High-
normal
Normal
Normal
Optimal
SBP
(mm Hg)
Normal
Border
- line
ISH
Stage 4
No recommendations
for SBP in JNC I
or JNC II
J NC 7
Stage 1
Stage 2
Prehyper-
tension
Normal
Stage 3
Stage 2
J NC BP Classifications: DBP
80
85
90
95
100
105
110
115
120
125
130
J NC I J NC II J NC III J NC IV J NC V J NC VI
Consider
therapy
Hyper-
tensive
Mild Mild Mild
Stage 1 Stage 1
Moderate Moderate Moderate
Stage 2
Severe
Severe
Severe
Stage 3 Stage 3
Stage 2
Stage 4
High-
normal
High-
normal
High-
normal
High-
normal
Normal Normal Normal Normal
Optimal
DBP
(mm Hg)
Optimal
J NC 7
Stage 1
Stage 2
Prehyper-
tension
Normal
J NC I. JAMA. 1977;237:255-261.
J NC II. Arch Intern Med. 1980;140:1280-1285.
J NC III. Arch Intern Med. 1984;144:1047-1057.
J NC IV. Arch Intern Med. 1988;148:1023-1038.
J NC V. Arch Intern Med. 1993;153:154-183.
J NC VI. Arch Intern Med. 1997;157:2413-2446.
J NC 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
J NC 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 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.
J NC 7. JAMA. 2003;289:2560-2572.
J NC 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
J NC 7. JAMA. 2003;289:2560-2572.
Heart Failure
Post MI
CAD risk
Diabetes Mellitus
Renal disease
Recurrent stroke
prevention

BB

ACEI

ARB

CCB

AA Diuretic

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 Tables
Developed;
Body of Evidence
Summarized
External Review
of Recommendation
Drafts; Revised
as Needed
Guidelines
Disseminated &
Implemented
Graded Evidence
Statements &
Recommendations
Developed
Expert Panel
Selected
Topic Area
Identified
Critical Questions
&Study Eligibility
Criteria 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 outcome
a
, 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
A
d
j
u
s
t
e
d

4
.
5
-
y

R
i
s
k

o
f

E
v
e
n
t
s

(
%
)
In-treatment SBP, deciles (mmHg)
Sleight P, et al. J Hypertens. 2009;27:1360-1369.
H
R
,

9
5
%

C
o
n
f
i
d
e
n
c
e

I
n
t
e
r
v
a
l
Primary study outcome
a
Composite of cardiovascular death, MI, stroke, or
hospitalization for congestive heart failure (CHF).
112 121 126 130 133 136 140 144 149 161
0
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
8.6
9.6
5.1
9.9
5.3
0
5
10
15
20
Primary Endpoint
Death/MI/
stroke/revascularization
All-cause
mortality
O
u
t
c
o
m
e

(
%
)
SBP > 140 mmHg
SBP 130140 mmHg
SBP < 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 Consensus
Documents
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
%patients
N=14 studies;43% >2 drugs
ACC Guidelines in Elderly 2011- J ACC 2011
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
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
RiskofcoronaryeventsinpeoplewithCKDcompared
withdiabetes:apopulationlevelcohortstudy
Tonelli Met.al.TheLancet2012;380:807812;Polonsky&BakrisLancet2012;380:783785
NHANES20032006
48monthFU
N=1,268,029
AssociationsofCKDwithmortalityandendstagerenaldisease
inindividualswithandwithouthypertension:ametaanalysis
Mahmoodi Ket.al.LancetSept242012
Ref.pt.=eGFR95withouthypertension
Interaction
Steno-2: Intensive Multiple Risk Factor
Management
Cardiovascular Events
Years of Follow-up
No. at Risk
Intensive therapy 80 72 65 61 56 50 47 31
Conventional 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 13
C
u
m
u
l
a
t
i
v
e

I
n
c
i
d
e
n
c
e

o
f

A
n
y

C
a
r
d
i
o
v
a
s
c
u
l
a
r

E
v
e
n
t

(
%
)
0
1
0
2
0
3
0
4
0
5
0
6
0
7
0
8
0
HR=0.41; p< 0.001
Absolute RR= 29%
HR for Total
Mortality: 0.54;
p=0.02
Absolute 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.
What is the Goal BP and Initial Therapy in Kidney
Disease or Diabetes to Reduce CV Risk?
* Indicates use with diuretic
Group
Goal BP
(mmHg)
Initial Therapy
ADA (2012) <130/80 ACE Inhibitor/ARB*
KDOQI (NKF) (2007) <130/80 ACE Inhibitor/ARB
ESH (2007+ 2009) <130/80 ACE Inhibitor/ARB*
KDOQI (NKF) (2004) <130/80 ACE Inhibitor/ARB*
JNC 7 (2003) <130/80 ACE Inhibitor/ARB*
Am. Diabetes Assoc (2003) <130/80 ACE Inhibitor/ARB*
Canadian HTN Soc. (2002) <130/80 ACE Inhibitor/ARB*
Am. Diabetes Assoc (2002) <130/80 ACE Inhibitor/ARB*
Natl. Kidney Foundation (2000) <130/80 ACE Inhibitor*
British HTN Soc. (1999) <140/80 ACE Inhibitor
WHO/ISH (1999) <130/85 ACE Inhibitor
JNC VI (1997) <130/85 ACE Inhibitor
30
SBP=systolic blood pressure. *Target blood pressure control groups in ACCORD defined as
<120 mm Hg (intensive) and <140 mm Hg (standard).
Copley J B, Rosario R. Dis Mon. 2005;51:548-614.
The ACCORD Study Group. N Engl J Med. 2010 Mar 14. [Epub ahead of print]
ALLHAT 138
HOT 138
ACCOMPLISH 132
ACCORD (intensive)* 119
ACCORD (standard)* 133
INVEST 133
IDNT 138
RENAAL 141
ABCD 132
UKPDS 144
MDRD 132
AASK 128
Multiple Medications Are Required to
Achieve BP Control in Clinical Trials
Hypertension
Diabetes
Kidney
disease
No. of BP medications
1 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+ persons
Mean follow-up 2.8 yrs
GuidetoKDIGOGrades
GRADE PATIENTS CLINICIANS POLICY
1
We
Recommend
Mostpeopleinyour
situationwouldwantthe
recommendedcourseof
actionandonlyafew
wouldnot.
Mostpatients
shouldreceivethe
recommended
courseofaction.
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.
I mpl i c at i ons
Grade Qualityof
Evidence
Meaning
A High
Weareconfidentthatthetrueeffectlies
closetothatoftheestimateofthe
effect.
B Moderate
Thetrueeffectislikelytobeclosetothe
estimateoftheeffect,butthereisa
possibilitythatitissubstantially
different.
C Low
Thetrueeffectmaybesubstantially
differentfromtheestimateoftheeffect.
D VeryLow
Theestimateofeffectisveryuncertain
andoftenwillbefarfromthetruth.
GuidetoKDIGOGrades
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
ACE inhibitors
or
ARBs
Calcium
antagonists
* 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