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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