2014 EVIDENCED BASED GUIDELINES FOR THE MANAGEMENT OF HYPERTENSION : A CRITICAL...
Transcript of 2014 EVIDENCED BASED GUIDELINES FOR THE MANAGEMENT OF HYPERTENSION : A CRITICAL...
2014 EVIDENCED BASED
GUIDELINES FOR THE
MANAGEMENT OF HYPERTENSION :
A CRITICAL REVIEW
Michelle Young-Brown, PharmD
1
2
Expanded Topic:
Review of 2014 Evidence-Based
Guideline for the Management of
High Blood Pressure in
Adults Report From the Panel
Members Appointed to the Eighth
Joint National Committee (JNC
8)
Objectives 3
Discuss how the development of the JNC 8 BP guidelines evolved and differ from previous hypertension guidelines.
Compare and contrast JNC 8 hypertension guidelines with the JNC 7
Discuss blood pressure goals/targets for the general population and goals for specific populations such as in diabetes, kidney disease, heart failure, and the elderly.
Discuss the key treatment recommendations of the guideline, how they differ from JNC 7 and the current controversy surrounding the guideline.
Introduction 4
The news rang out: JNC “Late” is finally here!
What we were expecting:
The Eighth Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC8).
Instead 2014 Evidenced Based Guidelines with much controversy & debate.
The Evolution of JNC 8 5
The NHBLI initiated a call for nominations to the Eighth
Joint National Committee (JNC 8).
440 nominations were received from which co-chairs
were selected.
The co-chairs along with representatives from NHBLI
formed the Guideline Executive Committee which
selected panel members.
The Evolution of JNC 8 cont’d
Panel members
appointed to JNC 8
were selected based
on expertise in the
following areas:
EXPERTISE # OF MEMBERS
Hypertension 14
Primary Care 6
Geriatrics 2
Cardiology 2
Nephrology 3
Nursing 1
Pharmacology 2
Clinical Trials 6
Evidenced Based
Medicine
3
Epidemiology 1
Informatics 4
Clinical guideline
development
4
6
The Evidence Review 7
JNC 8 focuses on the panel’s highest ranked
questions amongst the panel.
23 questions were compiled by panel members and
3 highest ranked were addressed.
1. In adults with HTN, does initiating
antihypertensive pharmacologic
therapy at specific BP thresholds
improves health outcomes?
2. In adults with HTN, does treatment
with antihypertensive pharmacologic
therapy at specific BP goals improves
health outcomes? .
3. In adults with HTN, do various
antihypertensive drugs or drug classes
differ in comparative benefits and
harms on specific health outcomes? .
The Evidence Review: Rationale for Question
Selection 8
The evidence supporting 140/90 mmHg as a
treatment threshold for the general population.
Treatment threshold or goal for patients with Diabetes,
CKD, CAD, stroke, other risks including older adults vs.
the general population.
Possible confusion between the threshold & treatment
goal.
Pharmacological treatments & health outcomes.
The Evidence Review 9
Focus: Adults 18 years and older with
hypertension including the following pre-
specified subgroups:
Diabetes
CAD, PAD
Heart Failure
Previous Stroke
CKD
Proteinuria
Older Adults, Smokers
Racial & Ethnic groups
The Evidence Review 10
The review of evidence was based on Randomized
Control Trials (RCTs).
Period Reviewed 1966-2009
The period December 2009 to August 2013 was
also reviewed to ensure that no major studies were
excluded.
The Evidence Review 11
RCT Criteria: (1) Major Study in the field (2) Had
at least 2000 participants (3) Multicentered (4)
Met all other inclusion/exclusion criteria.
The panel reviewed evidence statements and
clinical recommendations were voted on.
Evidence/literature reviewed by another body.
The guideline was submitted to external peer
review (20 reviewers) by NHBLI
JNC 7 Methodology 12
The NHBLI through their National High Blood Pressure Education Program (NHBPEP) organized a coordinating committee and appointed the executive committee and chair for JNC8.
MeSH terms were used to generate medline searches.
Peer-Reviewed scientific literature from January 1997 to April 2003.
The evidence was reviewed by the staff & executive committee.
JNC 7 13
Type of Evidence Evaluated
Randomized Controlled Trials
Retrospective Analysis
Prospective Studies
Cross Sectional Studies
Previous Review or Position Statement
Clinical Interventions (nonrandomized)
JNC 7 14
Looked at Patient Oriented Outcomes that Matter
(POEMS) and Disease Oriented Events.
Pre-hypertension was classified
Stage 2 & 3 were merged.
Comprehensive review of lifestyle modification
JNC 7 vs JNC 8 15
TOPIC JNC 7 2014 HTN
GUIDELINE
Methodology Nonsystematic
review by expert
committee.
Recommendations
based on consensus.
Critical questions.
Systematic review of
RCT.
Recommendations by
strict protocol.
Definitions Defines HTN & pre-
HTN
Not addressed
Lifestyle Literature review &
expert opinion
Endorses
recommendations of
Lifestyle Working
Group.
JNC 7 vs. JNC 8 cont’d 16
TOPIC JNC 7 2014 HTN GUIDELINE
Drug Therapy Recommends 5 drug
classes as well as
addressing compelling
indications
To be discussed
Scope of Topics BP Measurement,
evaluation, secondary
HTN, Resistant HTN,
Special Populations
Limited to 3 questions
that the panel judged as
having the highest
priority.
Review Process Reviewed by NHBPEP
(39 organizations, 7
federal agencies)
Reviewed by experts
from professional ,
public organizations &
federal agencies.
Treatment Algorithm:JNC8 17
Adults aged 18 years & older:
Implementation of lifestyle interventions
Setting blood pressure goals & initiating therapy
based on:
Age
Diabetes
Chronic Kidney Disease (CKD)
JNC 8 Treatment Goals 18
Age ≥ 60 years
Age ˂ 60 years
All Ages All Ages
Recommendation 1
19
In the general population aged ≥ 60 years, initiate pharmacological treatment to lower BP at ≥ 150/90 mmHg & treat to a goal of ≤150/90 mmHg (Grade A).
There is moderate to high quality evidence from RCT that treating BP to a goal of ≤ 150/90 mmHg in patients 60 years & older reduces stroke, Heart failure & Coronary Heart Disease (CHD).
Setting BP goals to ≤ 140/90 mmHg provides no additional benefits (low quality evidence).
Recommendation 2 20
In the general population ˂ 60 years, initiate
pharmacologic treatment at DBP ≥ 90 mmHg. For
ages 30-59 Grade A and for Ages 18-29 Grade E
(expert opinion).
Treating at a threshold DBP of 90 mmHg or higher
to a goal of ˂ 90 mmHg reduces cerebrovascular
events, heart failure and overall mortality. There is
evidence showing no benefit to decrease DBP to
either 80 mmHg or lower or 85 mmHg or lower.
Recommendation 3 21
In the general population younger than 60 years,
initiate pharmacological treatment to lower BP at SBP
of 140 mmHg or higher and treat to a goal SBP of
lower than 140 mmHg. [Grade E Expert Opinion].
There insufficient evidence from good or fair RCT to
support a specific SBP goal.
The absence of RCTs that compare the current target
with ↓ or ↑ standards in this age group presents no
compelling reason to change the recommendation.
Recommendation 4 22
In the population aged 18 years and older with CKD, initiate pharmacologic treatment to lower BP at 140/90 mmHg to a goal of ˂ 140/90 mmHg (grade E).
Adults aged 18-69 years with GFR (est/measured) ˂ 60ml/min/1.73m2 & albumin/creation >30mg/g
There is insufficient evidence to determine benefit to mortality, cardiovascular, cerebrovascular health outcomes with target ˂ 130/80 mmHg compared to ˂ 140/90 mmHg.
Recommendation 4 cont’d 23
No trial was found that looked at treatment to a lower BP goal e.g less than 130/80 lowering kidney or cardiovascular disease endpoints compared to higher targets such as less than 140/90.
Post hoc analysis of only one study (MDRD) indicated benefit from treatment to a lower BP goal (less than 130/80 mmHg) and this related to Kidney outcomes only (patients with proteinuria > 3g/24 hours).
Recommendation 4 cont’d 24
This recommendation does not take into account
adults > 70 years; as the tools to estimate GFR
have not been validated in this population and NO
outcome trials reviewed by the panel included large
numbers of adults aged 70 years or older with
CKD.
Recommendation 5 25
In the population aged 18 years & older with DM,
initiate pharmacologic treatment to lower BP at
140/90 mmHg or higher and treat to a goal of ˂
140/90 mmHg (Grade E).
Evidence form RCTs (three) demonstrate that
treatment to SBP ˂ 150 mmHg improves mortality,
cardiovascular and cerebrovascular health
outcomes.
Recommendation 5 cont’d 26
There were no studies comparing SBP 150 mmHg to 140 mmHg with respect to health outcomes.
Target goal selected on the basis of consistency.
The SBP goal of < 130mmHg is not supported by any RCT with 2 groups that compare SBP target of <140 mmHg to a lower threshold.
The ACCORD-BP trial compared goals of <140 mmHg to <120 mmHg and there was no difference in the primary or secondary outcomes excepting stroke.
Recommendation 5 cont’d 27
There is no evidence to support a DBP goal of < 80
mmHg.
The HOT trial (DBP 80 vs. 90 mmHg) showed a
reduction in CVD outcomes. BUT…..
The UKPDS trial showed significant ↓ stroke, HF, DM
endpoints & death.
UKPDS compared DBP 105 to 85 mmHg.
Impossible to determine effects of DBP goal < 85
mmHg vs. < 90 mmHg OR of benefits related to
SBP, DBP or both.
HOT Trial: Post Hoc
analysis of a small
subgroup (8%) of the
study population (#
unknown).
Recommendation 6 28
In the general nonblack population with diabetes,
initial antihypertensive treatment should include a
thiazide-type diuretic, CCB, ACEI or ARB (Grade B).
All 4 drug classes show comparable effects on
cardiovascular, cerebrovascular & kidney disease
outcomes & BP control.
For heart failure outcomes; initial tx with a thiazide-
type diuretic was found to be more effective than a
CCB or ACEI and ACEI more effective than a CCB
Recommendation 6 cont’d 29
ᵝ-Blockers are not recommended as initial treatment:
1 study showed a higher rate of composite cardiovascular
death, MI or stroke when compared to an ARB. In other
studies which compared beta blockers to the recommended
4 classes, they performed similarly. The panel determined
that there was insufficient evidence.
Recommendation 6 cont’d 30
Alpha Blockers were not recommended as first
line treatment:
One study demonstrated worse cerebrovascular, Heart
failure and combined cardiovascular outcomes compared
to diuretics.
No good or fair RCTs comparing α and ᵝ blocking
drugs, vasodilators, loop diuretics, aldosterone
antagonists & others to the 4 recommended drug
classes
Evidence Based Dosing of
Antihypertensive Drugs 31 DRUG INITIAL DAILY DOSE
(mg)
TARGET DOSE IN
RCTs (mg)
# of DAILY DOSES
Enalapril 5 20 2
Lisinopril 10 40 1
Losartan 50 100 1-2
Atenolol 25-50 100 1
Amlodipine 2.5 10 1
Hydrochlorthiazide 12.5-25 25-100 1-2
Indapamide 1.25 1.25-2.5 1
Valsartan 40-80 160-320 1
Recommendation 7 32
In the general black population, including those
with Diabetes, initial antihypertensive treatment
should include a thiazide-type diuretic or CCB
Weak evidence for those with DM
Thiazide-type diuretics was found to be more
effective than ACEI in improving cerebrovascular,
Heart Failure & combined cardiovascular outcomes.
CCB recommended over ACEI in blacks-51% higher
stroke of stroke in ALLHAT
BP Control
Recommendation 8 33
In the population aged 18 years or older with CKD & hypertension, initial (& add-on) anti-hypertensive therapy should include an ACEI or ARB to improve kidney outcomes (Grade B).
This applies to ALL CKD patients.
There were no studies demonstrating the benefits of Direct Renin Inhibitors on kidney or cardiovascular outcomes.
What of Black CKD patients?
Monitoring recommended
Recommendation 9 34
The initial evaluation period goal attainment should
be within one month.
The process should be continuous in order assess
progress & goal attainment & to facilitate
adjustments in therapy
ACEI & ARB should NOT be used together.
If the treatment strategy outlined is not effective, a
specialist should be sought.
Treatment Strategies 35
Maximize the first medication before adding the
second. The second drug should be titrated to the
maximum OR
Add second medication before reaching max. dose
of first medication. Both drugs should be titrated to
the max before adding a third OR
Start with 2 medication classes separately or as a
fixed dose combination.
Treatment Strategies cont’d 36
Consider starting with 2 drugs if SBP > 160 mmHg and or DBP > 100 mmHg OR if SBP > 20 mmHg and or DBP > 10 mmHg above goal.
Addition of other medication classes such as beta blockers, aldosterone antagonists or others are recommended only after all the above steps have been tried & reinforcemement of medication & lifestyle adherence.
At this stage the patient can be referred to a expert in Hypertension management.
Guideline Comparison 37
GUIDELINE POPULATION GOAL BP/mmHg INITIAL TX
OPTIONS
2014 HTN –JNC8 General ≥ 60 years < 150/90 Non-black T-D,
CCB,ACEI ,ARB
General <60 years < 140/90 Black- T-D, CCB
Diabetes < 140/90 T-D, CCB,ACEI ,ARB
CKD < 140/90 ACEI or ARB
ESH/ESC 2013 General nonelderly < 140/90 BB, D, CCB, ACEI,
ARB
Gen. Elderly <80 yr < 150/90
Gen. ≥ 80 years < 150/90
Diabetes < 140/85 ACEI or ARB
CKD no proteinuria < 140/90 ACEI or ARB
CKD + proteinuria < 130/90
Guideline Comparison cont’d 38
Canadian Hypertensive Education Program (CHEP)
2013 guidelines.
Population above & below 80 years & CKD with similar
goals to JNC8. Excepting diabetics where the goal is <
130/80 mmHg.
Beta blockers recommended if < 60 years
ACEI, ARB, DHPCCB recommended for DM with no CVD
risk factors
ACEI or ARB for Diabetics with additional CVD risk
factors
Guideline Comparison cont’d 39
The NICE 2011 guidelines recommends < 150/90
mmHg for adults over 80 years
ACEI or ARB if < 55 years & CCB if > 55 years
KDIGO 2012 recommends ACEI or ARB & sets a
goal of < 130/80 mmHg for patients with
proteinuria
ADA 2014 recommends a BP goal of < 140/80
mmHg & advises that a target SBP of < 130 mmHg
may be appropriate for some patients.
Controversies 40
NHBLI commissioned JNC8 in 2008 but announced
in early 2013 that they were handing it over to the
ACA & AHA.
The JNC8 members went to press without ACC/AHA
These guidelines are not sanctioned by the NHBLI or
the ACC/AHA
The JNC8 panel stated that they did not seek
approval of the guideline but individuals, societies
etc. to read, digest & decide to implement or not.
Controversies 41
The JNC 8 guidance adheres much more closely to
quality standards published by the Institutes of
Medicine (IOM) in 2011 (Clinical Practice
Guidelines We Can Trust) than it does the JNC 7
document: a strength.
Dr Harold C Sox (Dartmouth Institute for Health Policy and
Clinical Practice, Hanover, NH)
Controversies 42
The loosening of targets is as much based on a lack
of evidence as it is on new evidence.
"I think this will instill some debate: did they get the
thresholds right?“
Dr Eric Peterson (Duke University, Durham, NC) and
colleagues (all associate or senior editors at JAMA)
Controversies 43
No observational studies, systematic reviews or meta-
analysis were included
Initiation on therapy in low risk people not addressed.
Age Distinction of 60 years
Disagreement with the evidence used
Personal Rant?
David K. Cundiff - internal medicine physician and author
of “ Money Driven Medicine Test and Treatments That
Don’t Work”.
Conclusion 44
This guideline is not comprehensive & the scope was limited to 3 specific questions.
All available evidence was not considered, only RCTs.
It was noted that clinicians use other factors to make therapeutic decisions such as treatment adherence & medication costs.
Lifestyle treatments to reduce BP should be employed.
Guidelines are not a substitute for good clinical judgment.
Reference 45
The seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation & Treatment of High Blood Pressure https://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm
Wood, Shelly (2013). JNC 8 At Last! Guidelines Ease up on BP Thresholds, Drug Choices http://www.medscape.com/viewarticle/817991#2
Kundiff, David (2014). A Call to Retract the JNC8 Hypertension Guidelines . Retrieved from http://www.kevinmd.com/blog/2014/01/call-retract-jnc8-hypertension-guidelines.html
References cont’d 46
James PA , Oparil S, Carter BL, et al. 2014 Supplement to 2014 Evidence-based guideline for the management of high blood pressure in adults: report by the panel appointed to the Eighth Joint National Committee (JNC 8) JAMA. doi:10.1001/JAMA.2013.284427.
American Diabetes Association. (2014). Standard of Medical Care in Diabetes- 2014 Diabetes Care Volume 37, Supplement 1, January 2014
James PA , Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report by the panel appointed to the Eighth Joint National Committee (JNC 8) JAMA. doi:10.1001/JAMA.2013.284427
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