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
Border
- line
No recommendations
for SBP in JNC I
or JNC II
JNC I
JNC II
ISH
Border
- line
Stage 2
Stage 2
Stage 2
Stage 1
Stage 1
Stage 1
Highnormal
Highnormal
Normal
Prehypertension
Optimal
Optimal
Normal
JNC V
JNC VI
JNC 7
Normal
Normal
JNC III
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.
Stage 3
JNC IV
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
Hypertensive
Consider
therapy
JNC I
Severe
Severe
Severe
Moderate
Moderate
Moderate
Mild
JNC II
Mild
Stage 3
Stage 3
Stage 2
Stage 2
Stage 2
Stage 1
Stage 1
Stage 1
Mild
Highnormal
Highnormal
Highnormal
Highnormal
Normal
Normal
Normal
Normal
Prehypertension
Optimal
Optimal
Normal
JNC VI
JNC 7
JNC III
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 JNC V
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
Stage 2 Hypertension
(SBP 140–159 or DBP 90–99 mmHg)
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
(SBP >160 or DBP >100 mmHg)
2-drug combination for most (usually
thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
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.
Drug(s) for the compelling
indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB, CCB)
as needed.
JNC 7 Compelling Indications
Heart Failure
Diuretic
BB
ACEI
ARB






Post MI



Diabetes Mellitus






Recurrent stroke
prevention

AA


CAD risk
Renal disease
CCB



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)
Level A
(Multiple
randomized
clinical trials)
Level B
(Single
randomized trial
or
nonrandomized
studies
Level C
(Consensus
opinion, case
studies, or
standard of care)
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)
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
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
Expert Panel
Selected
Studies Quality Rated;
Data Abstracted
Critical Questions
&Study Eligibility
Criteria Identified
Literature Searched;
Eligible Studies
Identified
Graded Evidence
Statements &
Recommendations
Developed
External Review
of Recommendation
Drafts; Revised
as Needed
Guidelines
Disseminated &
Implemented
NHLBI Evidence Quality Rating and
Recommendation Strength
Evidence Quality
• High
– Well-designed and
conducted RCTs
• Moderate
Recommendation Strength
A – Strong
B – Moderate
C – Weak
– 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
Adjusted 4.5-y Risk
of Events (%)
25
2.5
20
2
15
1.5
10
1
5
0.5
0
112
121 126 130 133 136 140 144 149 161
HR,
95% Confidence Interval
3
Primary study outcome
0
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
aComposite
of cardiovascular death, MI, stroke, or
hospitalization for congestive heart failure (CHF).
Sleight P, et al. J Hypertens. 2009;27:1360-1369.
CV outcomes from the ACCOMPLISH trial
OUTCOMES: (MI, stroke, revascularization, all-cause mortality)
20
SBP > 140 mmHg
Outcome (%)
16.3
SBP 130–140 mmHg
SBP < 130 mmHg
15
10
9.6
9.9
5.1
5
0
8.6
Primary Endpoint
Death/MI/
stroke/revascularization
Weber M et.al. submitted Am J Med.
All-cause
mortality
5.3
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
(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)
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
Risk of coronary events in people with CKD compared with diabetes: a population‐level cohort study
NHANES 2003‐2006
48 month FU
N=1,268,029 Tonelli M et.al. The Lancet 2012;380:807‐812; Polonsky& Bakris Lancet 2012;380:783‐785
Associations of CKD with mortality and end‐stage renal disease in individuals with and without hypertension: a meta‐analysis
Interaction
Mahmoodi K et.al. Lancet –Sept 24 2012
Ref. pt.= eGFR 95 without hypertension
Steno-2: Intensive Multiple Risk Factor
Management
Cumulative Incidence of Any
Cardiovascular Event (%)
Cardiovascular Events
HR=0.41; p< 0.001
Absolute RR= 29%
8
0
7
0
6
0
5
0
4
0
3
0
2
0
1
0
0
Conventional
Therapy
HR for Total
Mortality: 0.54;
p=0.02
Absolute RR= 20%
Intensive
Therapy
0
1
2
3
4
5
6
7
8
9
10
11
12
13
Years of Follow-up
No. at Risk
Intensive therapy
Conventional therapy
80
80
Gaede P, et al. NEJM. 2008;358:580-591.
72
70
65
60
61
46
56
38
50
29
47 31
25 14
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.
WhatistheGoalBPandInitialTherapyinKidney
DiseaseorDiabetestoReduceCVRisk?
Group
Goal BP
(mmHg)
Initial Therapy
ADA(2012)
<130/80
ACEInhibitor/ARB*
KDOQI(NKF)(2007)
<130/80
ACEInhibitor/ARB
ESH(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
<130/85
ACEInhibitor
* IndicatesJNCVI(1997)
use with diuretic
30
Multiple Medications Are Required to
Achieve BP Control in Clinical Trials
Trial
Hypertension
Diabetes
Kidney
disease
SBP achieved
(mm Hg)
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
1
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]
2
3
No. of BP medications
4
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.
Guide to KDIGO Grades
Implications
GRADE
PATIENTS
CLINICIANS
POLICY
1
We
Recommend
Most people in your
situation would want the recommended course of action and only a few would not.
Most patients should receive the
recommended course of action.
The recommendation can be evaluated as a candidate for developing a policy or a performance
measure.
2
We 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 needs
help to arrive at a
management decision consistent with her or his values and preferences.
There is a need for
substantial debate and involvement of stakeholders.
Guide to KDIGO Grades
Grade
Quality of
Evidence 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.
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 2D
Kidney 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 2D
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