2014 Evidence-Based Guidelines for

the Management of

High Blood Pressure in Adults

JNC 8Paul A.James,MD, et al JAMA.2013.284427

Introduction

Hypertension is the most common,important preventable

condition seen in primary care and leads to MI,Stroke,Renal

failure, and death if not detected early and treated appropriately.

Present Days Everything to be EVIDENCE BASED…!!!!!

E- directed therapy

JNC 8..?

THE EVIDENCE BASED GUIDELINES

Rigorous,evidence based approach to recommend treatment

thresholds,

goals,and medications in the management of HTN in adults.

Evidence was from RCTs,the gold standard for determining efficacy

and effectiveness.

Evidence quality rating

RECOMMENDATIONS

1-5 –address questions 1 and 2 concerning thresholds and

goals for BP treatment.

6,7,8 – address question 3 concerning selection of

antihypertensive drugs.

9 – summary of strategies based on expert opinion for starting

and adding antihypertensive drugs.

RECOMMENDATION 1

§ In the general population aged ≥60 years,

initiate pharmacological treatment to lower BP at

SBP of ≥150 mm Hg or

DBP of ≥ 90mm Hg and

treat to a goal

SBP < 150 mm Hg and

DBP <90 mmHg.

Strong recommendation – Grade A.

Goal BP evidence statement is from…

• HYVET

• Syst-Eur (The Systolic Hypertension in Europe Trial)

• SHEP(Systolic Hypertension in the Elderly Program)

• JATOS (Japanese Trial to assess Optimal Systolic blood

pressure in elderly hypertensive patients)

• VALISH (VALsartan in elderly Isolated Systolic Hypertension

Study)

• CARDIO-SIS

High risk groups

• Black persons

• Those with CVD including stroke

• Multiple risk factors

Corollary Recommendation

§ In the General Population aged ≥60 yrs,

If pharmacological treatment for high BP results in lower

achieved SBP (for example <140 mm Hg) and

treatment is not assosciated with adverse effects on health or

quality of life,

treatment does not need to be adjusted.

Expert opinion – Grade E.

• In HYVET,SHEP trial,the average treated SBP was 143

to144mmHg.Many participants achieved an SBP lower than 140

mm Hg with treatment that was generally tolerated.

• Two other trials JATOS,VALISH suggest there was no benefit

for an SBP goal lower than 140 mmHg,but the confidence

intervals around the effect sizes were wide and did not exclude the

possibility of a clinically important benefit.

RECOMMENDATION 2

§ In the general population < 60 yrs,

Initiate pharmacological treatment to lower BP

at DBP of ≥90 mmHg and

treat to a goal

DBP of lower than 90 mmHg.

For ages 30-59 years,Strong recommendation -Grade A.

For ages 18-29 years.Expert opinion –grade E.

DBP trials

• HDFP(Hypertension Detection and Follow uP)

• Hypertension – Stroke Cooperative

• MRC

• ANBP

• VA Cooperative

• Treatment to a lower DBP goal lower than 90 mm Hg reduces

cerebrovascular events,HF,overall mortality.

• No benefit of treatment to a target DBP of 80,85 mm Hg compared

to 90 mm Hg – HOT trial(not statistically significant in outcomes).

In adults< 30 yrs

• There are no good or fair quality RCTs that assessed the benefits

of treating elevated DBP on health outcomes.

.

• DBP threshold and goal should be the same as in 30-59 yrs.

(panel’s opinion)

RECOMMENDATION 3

§ In the General Population younger than 60years,

initiate pharmacological treatment to lower BP

at SBP of ≥140 mm Hg and

treat to a goal SBP of < 140 mm Hg.

Expert opinion – Grade E.

Reasons for 140 mm Hg SBP

1.In the absence of any RCTs that compared the current SBP standard of

140 mm Hg with another higher or lower standard in this age group,there

was no compelling reason to change current recommendations.

2.In the DBP trials (the benefit of treating DBP to <90 mm Hg),many of

the study participants who achieved target DBP were also likely to have

achieved SBP <140 mmHg with Rx,not possible to determine the outcome

benefits were due to lowering of DBP,SBPor both.

RECOMMENDATION 4

§ In the Population aged 18 years or older with CKD,

Initiate pharmacological treatment to lower BP at

SBP of ≥ 140 mm Hg

or

DBP of ≥ 90 mmHg

and

treat to goal

SBP of < 140 mm Hg and

DBP < 90 mm Hg.

Expert opinion – grade E.(Younger <70 yrs with eGFR or measured GFR <60 ml/min/1.73m2

People of any age with albuminuria >30mgalb/g of creatinine)

• In adults <70 yrs with CKD,the evidence is insufficient to determine

if there is a benefit in mortality,or cardiovascular or CV health

outcomes with antihypertensive drug therapy to a lower BP goal(ex

<130/80 mm Hg)compared with a goal of <140/90 mm Hg).

• Moderate quality evidence with regard to no benefit in slowing the

progression of kidney disease from treatment with antihypertensive

drug therapy to a lower BP goal <130 /80 compared to <140/80 mm

Hg).

Effect of antihypertensive drug therapy on change in GFR or time to development of

ESRD• 3 trials

• 1 trial addressed cardiovascular disease end points.

• 2 trials AASK and MDRR used MAP and different targets by age.

• 1 trial(REIN 2) using only DBP goals.

• None of the trials showed that treatment to a lower BP goal (for

example,<130/80 mm Hg) significantly lowered Kidney or

CardioVascular Disease end points compared with a goal of

<140/90 mm Hg.

For patients with proteinuria > 3g/24,post hoc analysis from

MDRD indicated benefit from treatment to a lower BP goal

<130/80 mm Hg and this related to kidney outcomes only.

Age >70 yrs

• No recommendation for pts >70 yrs

with GFR < 60ml/min/1.73m2

• Commonly used estimating equations for GFR have not been

vaildated in older adults.

• Not significant number of patients in outcome trials analysed.

• Diagnostic criteria for CKD do not consider age related decline

in kidney function as reflected in estimated GFR.

• Antihypertensive treatment should be individualized based on

frailty,co morbidities and albuminuria.

RECOMMENDATION 5

§ In the Population aged 18 years or older with diabetes,

initiate pharmacological treatment to lower BP at

SBP of ≥ 140 mm Hg or

DBP of ≥90 mm Hg

and treat to a

goal SBP < 140 mm Hg

goal DBP < 90 mm Hg

Expert opinion Grade E.

• SBP of < 150 mm Hg improves cardiovascular and cerebrovascular

health outcomes and lowers mortality (SHEP,Syst –Eur,UKPDS).

No RCTs addressed whether Rx to <140mmHg is beneficial compared

to <150 mmHg.

• SBP <140 mm Hg is supported by ACCORD BP trial,in which the

control group used this goal and had similar outcomes compared with a

lower goal.

• ADVANCE trial tested the effects of Rx to lower BP on major

macrovascular and microvascular events in adults with diabetes who

were at increased risk of CVD,but the study didn’t meet the inclusion

criteria because participants were eligible irrespective of baseline BP

and there were no randomized BP treatment thresholds or goals.

SBP goal of <130 mm Hg

• Not supported by any RCT.

• Only trial was ACCORD BP trial which compared an SBP treatment goal

of <120 mm Hg with a goal <140 mm Hg. – no difference in the primary

outcome,a composite of CV death,non fatal MI,and non fatal stroke.

• No differences in any of the secondary outcomes except for a reduction in

stroke.

• Incidence of stroke in the group treated to <140 mm Hg was much lower

than expected,the difference being 0.21% per year.

• No sufficient evidence could be provided by the trial.

• In the HOT trial,which is frequently cited to support a lower

DBP goal,investigators compared a DBP goal of 90 mmHg or

lower vs a goal of 80 mm Hg or lower.

• The lower goal was associated with a reduction in a

composite CVD outcome,but this was a post hoc analysis of a

small group(8%) of the study population that was not

prespecified,as a result the evidence was graded as low

quality.

• UKPDS,had a BP goal of <150/85 mm Hg in the more

intensively treated group compared with a goal of lower than

180/105 mmHg in the less intensively treated group.

• UKPDS did show that treatment in the lower goal BP group

was associated with a signficantly lower rate of

stroke,HF,diabetes related end points,and deaths related to

diabetes.(80 mm Hg vs 105 mmHg)(mixed SBP and DBP

study).

RECOMMENDATION 6

§ In the General NonBlack population,including those with

Diabetes,

initial AntiHypertensive treatment should include a

Thiazide -type Diuretic,

Calcium Channel Blocker(CCB),

Angiotensin Converting Enzyme inhibitor(ACEI),or

Angiotensin Receptor Blocker(ARB).

Moderate recommendation –GradeB.

• Only RCTs that compared one class of antihypertensive

medication to another and assessed the effects on health

outcomes were reviewed.

• Placebo controlled trials were not included.

• Treatment of HTN with antihypertensive medications reduces CV

mortality or CV events.(VA cooperative trial,HDFP,SHEP) all

trials used thiazide type diuretics compared with placebo.

• Additional evidence that BP lowering reduces risk comes from

trials of B blocker vs placebo and CCB vs placebo.

• Initial treatment with a thiazide type diuretic was more effective

than a CCB or ACEI.

• ACEI was more effective than a ARB in improving HF outcomes.

• B blockers are not recommended as initial treatment of HTN

because in one study use of B blockers resulted in a higher rate of

primary composite outcome of CV death,MI,or Stroke compared

to use of an ARB,a finding that was largely driven by an increase

in stroke.(LIFE study : Losartan vs Atenolol).

• Alpha blockers were not recommended as first line

therapy(ALLHAT trial).

Not recommended as first line drugs

• Dual alpha1 +b blocking agents (Carvedilol)

• Vasodilating b blocking agents (Nebivolol)

• Central a2 adrenergic agonists (Clonidine)

• Direct vasodilators (Hhydralazine)

• Alodsterone receptor antagonists (Spironolactone)

• Peripherally acting adrenergic antagonists (Reserpine)

• Loop diuretics(Furosemide)

ONTARGET trial was not eligible because Hypertension was

not required for inclusion in the study.(Telmisartan,Ramipril).

RECOMMENDATION 7

§ In the General Black population,

including those with Diabetes,

initial antihypertensive treatment should include a

thiazide – type diuretic or CCB.

For general black population:Moderate Recommendation –GradeB.

For black patients with diabetes:Weak recommendation –GradeC.

• A thiazide type diuretic was shown to be more effective in

improving CerebroVascular,HF,combined CardioVascular outcomes

compared to an ACEI in the black subpatient group(diabetic and

non diabetics)ALLHAT trial.

• CCB not effective over thiazide diuretic in preventing HF in black

population.

• CCB preferred over ACEI in blacks – 51% higher rate (relative

risk,1.51:95%CI,1.22-1.86) of stroke in pts with the use of ACEI

ALLHAT trial.

• ACEI less effective than CCB in reducing BP in blacks.

• No studies comparing diuretics,CCBs vs BB,ARBs,Renin

angiotensin inhibitors in black population.

RECOMMENDATION 8

§ In the population aged 18 years or older

with CKD and hypertension,

initial (or add-on) antihypertensive treatment should include

ACEI or ARB to improve kidney outcomes.

This applies to all CKD patients with hypertension regardless

of race or diabetes status.

Moderate Recommendation – GradeB.

• Recommendation applies to CKD pts with or without proteinuria.

• Less evidence favouring ACEI/ARB for cardiovascular outcomes in

patients with CKD.

• Neither ACEI/ARBs improved CV outcomes for CKDpts compared

with a BB or CCB.

• ARB improved HF outcomes compared with a CCB(IDNT) trial –

population was restricted to pts with diabetic nephropathy with

proteinuria.

• No RCTs in the evidence review that compared directly ACEI./ARB

for any CV outcome.

• AASK study showed the benefit of an ACEI on kidney outcomes

in black patients with CKD and provides additional evidence that

supports ACEI use in that population.

• Trials not restricted to patients with Hypertension,showing

benefits of ACEI/ARBs are not included.

• Direct renin inhibitors are not included – no studies demonstrated

their benefits on kidney or CV outcomes.

What if patient is a black and having CKD?

• In black patients with CKD and proteinuria,an ACEI or ARB is

recommended as initial therapy because of the higher likelihood

of progression to ESRD. AASK trial.

JAMA.2002;288(19):2421-2431

• In black patients with CKD but without proteinuria,the choice

for initial therapy is less clear and includes a thiazide- type

diuretic,CCB,ACEI or ARB.

• ACEI /ARB can be used as an initial drug or second line drug.

Patients older than 75 yrs

• No evidence to support renin angiotensin system inhibitor

treatment in those older than 75 yrs.

• Use of thiazide type diuretic or CCB is also an option for

individuals with CKD in this age group.

Trials results have an effect…

The placebo effect…

RECOMMENDATION 9

If goal BP is not reached within a month of treatment,

Increase the dose of the initial drug or

add a second drug from one of the classes in recommendation6 (thiazide- type diuretic,CCB,ACEI,ARB).

If goal BP cannot be reached with 2 drugs,

add and titrate a third drug from the list provided. Donot use an ACEI and ARB together in the same patient. If goal BP cannot be reached using the drugs in recommendations,

because of a contraindication or the need of > 3 drugs to reach goal BP,antihypertensive drugs from other classes can be used.

Referral to a hypertension specialist. Expert opinion –GradeE.

Peculiarities of recommendation 9

• In response to a perceived need for further guidance to assist

in implementation of recommendation 1-8.

• Based on strategies used in RCTs that demonstrated improved

patient outcomes,expertise and clinical experience of panel

members.

• Not developed in response to 3 critical questions.

• No evidence about which strategy improved outcomes.

Discussion

• The recommendations based on RCT evidence in this

guideline differ from recommendations in other currently

used guidelines supported by expert consensus.

• JNC7 and other guidelines recommend treatment to lower BP

goals in patients with diabetes and CKD based on

observational studies.

• ADA have raised the SBP goals to values that are similar to

those recommended in this evidence based guideline.

Patients want to be assured that BP

treatment will reduce their disease burden.

Clinicians want guidance on hypertension management using the best scientific evidence.

Clinical guidelines are at the intersection between research evidence and clinical actions that can improve patient outcomes.

Expertise in HTN (n=14),

Primary care (n=6),

Geriatrics (n=2),

Cardiology (n=2),

Nephrology (n=3)

Nursing =1,

Pharmacology n=2,

Clinical trials n =6,

EBM ,n=3

Senior scientist from NIDDK

Senior medical officer from NHLBI

PANEL MEMBERS

Review in January 2013 NHLBI

20 reviewers 16 federal agencies

Reviewed and discussed by panel

MARCH TO JUNE 2013

-revised document

THE PROCESS

Questions guiding the Evidence review

§ 3 highest ranked questions related to high BP management identified through a modified DELPHI technique.

Nine recommendations were made.

1.Thresholds for pharmacological management

2.Goals for pharmacological management.

3.Whether particular antihypertensive drugs or drug classes improve important health outcomes compared with other drug classes.

The Evidence Review

• Adults aged 18yrs or older with HTN

• Prespecified sub groups –

Diabetes,CAD,PAD,HF,Stroke,CKD,Proteinuria,older

adults,men and women,racial and ethnic groups,smokers.

• Sample sizes smaller than 100 were excluded.

• Follow up < 1 yr were excluded.(unlikely to yield enough

information regarding health related outcomes to permit

interpretation).

• Important health outcomes information

• Overall mortality ,CVD mortality,CKD related mortality.

• MI,HF,hospitalization for HF,stroke.

• Coronary revascularization (CABG,coronary angioplasty,stent

placement),doubling of creatinine level,halving of GFR.

Second review

1.Study was a major study in hypertension (ACCORD-BP,SPS3)

2.Study had atleast 2000 participants.(low event rates in ACCORD)

3.Study was multicentered.

4.Study met all other inclusion/exclusion criteria.

• No additional clinical trials met the previously described inclusion criteria.

• Studies were included if rated as good or fair.

Why only RCTs ?????

Less subject to bias

Gold standard for determining efficacy and effectiveness.

Original publications of eligible RCTs.

January 1,1966 through December 31,2009.

PubMed and CINAHL between December 2009 and August 2013.

HISTORY OF JNC8• Originally constituted as the “EIGHTH JOINT NATIONAL COMMITTEE

ON THE PREVENTION,DETECTION,EVALUATION,AND

TREATMENT OF HIGH BLOOD PRESSURE(JNC 8)”.

• In June 2013,NHLBI announced its decision to discontinue developing

clinical guidelines including those in process,instead partnering with selected

organizations that would develop the guidelines.

Not an NHLBI sanctioned report and does not reflect the views of NHLBI.

Circulation 2013;128(15):1713-1715.

Limitations

´ Not a comprehensive guideline

´ Limited in scope ( focused evidence review to address the 3

specified questions).

´ Numerous comorbidities with HTN not addressed.

´ Adherence and medication costs.

´ Observational studies,systematic reviews,or meta –analysis.

´ RCTs with participants with normal BP were excluded.

´ Recommendations donot apply to those without HTN.

´ Treatment related adverse effects on health outcomes.

Conclusions

• Not redefined high BP .

• Relationship between natural occuring BP and risk is linear

down to very low BP,but the benefit of treating to these lower

levels with antihypertensive drugs is not established.

• For all patients with HTN ,the benefits of a healthy diet,wt

control,regular exercise cannot be overemphasized. – reduce

medication needs.

• Recommendations by 2013 Lifestyle Work Group.