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JNC 8: A REVIEW OF THE LONG-AWAITED/MUCH-ANTICIPATED

HYPERTENSION GUIDELINES

Tiffany Dickey, PharmDAssistant Professor, UAMS COP Clinical Pharmacy Specialist, Mercy Hospital Northwest AR

DISCLOSURE

I have nothing to disclose.

PHARMACIST OBJECTIVES

1. Identify blood pressure goals set by JNC 8 for adult patients.

2. Compare and contrast JNC 8 recommendations with other current guidelines.

3. Recommend appropriate therapy for hypertensive patients according to JNC 8.

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TECHNICIAN OBJECTIVES

1. Define hypertension.

2. Identify JNC 8.

3. Identify medications used to treat hypertension.

THE FACTS

Hypertension is the most common chronic condition addressed by primary care providers� In 2010 ~78 million US adults with HTN, 50% uncontrolled

Close relationship exists between blood pressure levels and the risk of cardiovascular events, strokes, and kidney disease� Risk is lowest at 115/75 mmHg

� For every � of 20 mmHg in SBP or 10 mmHg in DBP the risk of major CV and stroke events double

� Lack of evidence to justify treating HTN down to 115/75

The Journal of Clinical Hypertension. 2014;16:14-26.

THE DRAMA

Eighth Joint National Committee of Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8)� Appointed in 2008 by the National Heart, Lung, and Blood Institute (NHLBI)

June 2013� NHLBI announced that the agency was withdrawing from issuing guidelines itself and would instead

collaborate with “partner organizations”

August 2013� AHA and ACC reached an agreement with NHLBI to “spearhead” development of 3 sets of practice

guidelines – HTN, cholesterol, obesity

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THE DRAMA CONTINUES

JNC 8 panel members weren’t comfortable with “the idea of shopping our guideline around prior to publication and getting an endorsement.” � AHA/ACC failed to reach an agreement with JNC 8 panel members

The big deal...� Many experts with a very significant stake in the recommendations were excluded from the process of generating

the guideline

Guidelines published in JAMA as a “Report from the Panel Members Appointed to JNC 8”

“Unlike the previous JNC reports, this one will be seen as interesting, but not as persuasive.”

THE EVIDENCE

Randomized controlled trials from 1966-2009

Adults >18 years of age with hypertension

Excluded if sample size <100 participants

Excluded if follow-up period <1 year

Observational studiesSystematic reviewsMeta-analyses

JAMA. 2014;311(5):507-520.

QUALITY RATING AND RECOMMENDATION STRENGTH

Evidence quality� High – Well designed and executed RCTs

� Moderate – RCTs with minor limitations

� Low – RCTs with major limitations

Strength of recommendations� Grade A – Strong

� Grade B – Moderate

� Grade C – Weak

� Grade D – Against

� Grade E – Expert opinion

� Grade N – No recommendation

JAMA. 2014;311(5):507-520.

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QUESTIONS ADDRESSED

1. In adults with hypertension, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes?

2. In adults with hypertension, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes?

3. In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes?

JAMA. 2014;311(5):507-520.

CLASSIFICATION OF BLOOD PRESSURE

Blood pressure

classification

Systolic blood

pressure

Diastolic blood

pressure

Normal <120 mmHg and <80 mmHg

Prehypertensive 120–139 mmHg or 80–90 mmHg

Stage 1 hypertension

140–159 mmHg or 90–99 mmHg

Stage 2 hypertension

>160 mmHg or >100 mmHg

ACCORDING TO JNC 7…

JAMA. 2003;289(19):2560-2571.

RECOMMENDATION 1

In the general population aged >60 years, initiate pharmacologic treatment to lower blood pressure at SBP >150 mmHg or DBP >90 mmHg and treat to a goal SBP <150 mmHg and goal DBP <90 mmHg.

(Strong Recommendation – Grade A)

� In the general population aged >60 years, if pharmacologic treatment for high blood pressure results in lower achieved SBP (eg. <140 mmHg) and treatment is not associated with adverse effects on health or quality of life, treatment does not need to be adjusted. (Expert Opinion – Grade E)

JAMA. 2014;311(5):507-520.

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SUPPORTING EVIDENCE: SHEP

Treatment of HTN in patients >60 years of age � Goal BP for patients with SBP >180 = 160 mmHg

� Goal BP for patients with SBP 160-179 = reduction of 20 mmHg

Primary outcome:� Fatal or nonfatal stroke

Secondary outcomes:� Cardiovascular and coronary morbidity and

mortality, all cause mortality, quality of life measures

JAMA. 1991;265(24):3255-3264.

SUPPORTING EVIDENCE: SHEP

JAMA. 1991;265(24):3255-3264.

P = 0.0003

SUPPORTING EVIDENCE: HYVET

Treatment of HTN in patients >80 years of age

Primary outcome:� Fatal or nonfatal stroke

Secondary outcomes:� Death from any cause, death from

cardiovascular causes, death from stroke

N Engl J Med. 2008;358(18):1887-1898.

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SUPPORTING EVIDENCE: HYVET

Study conclusion:

“The results support a target blood pressure of 150/80 mmHg in patients receiving treatment…”

N Engl J Med. 2008;358(18):1887-1898.

SUPPORTING EVIDENCE: JATOS

Hypertens Res. 2008;31:2115-2127.

Treatment of HTN in patients 65-85 years of age� Strict treatment: SBP <140 mmHg

� Mild treatment: SBP <160, >140 mmHg

Primary outcome:� Combined incidence of cardiovascular

disease and renal failure

Secondary outcomes:� Total deaths, safety problems

SUPPORTING EVIDENCE: JATOS

Hypertens Res. 2008;31:2115-2127.

Study conclusion: “The results of our study suggest that a reduction of mean SBP to 146 mmHg may be adequate in most elderly hypertensive patients…”

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RECOMMENDATION 2

In the general population <60 years, initiate pharmacologic treatment to lower blood pressure at DBP >90 mmHg and treat to a goal DBP <90 mmHg.

(For ages 30-59 years, Strong Recommendation – Grade A)

(For ages 18-29 years, Expert Opinion – Grade E)

JAMA. 2014;311(5):507-520.

SUPPORTING EVIDENCE: HOT

Assess the optimum target diastolic blood pressure in patients with baseline DBP of 100-115 mmHg (ages 50-80 years)� <90 mmHg

� <85 mmHg

� <80 mmHg

Primary outcome:� Asses the association between major

cardiovascular events and the target blood pressures

� Non-fatal MI, non-fatal stroke, cardiovascular death

Lancet. 1998;351(9198):1755-1762.

SUPPORTING EVIDENCE: HOT

Lancet. 1998;351(9198):1755-1762.

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RECOMMENDATION 3

In the general population <60 years, initiate pharmacologic treatment to lower blood pressure at SBP >140 mmHg and treat to a goal SBP <140 mmHg.

(Expert Opinion – Grade E)

� “The panel found insufficient evidence from good- or fair-quality RCTs to support a specific SPB threshold or goal for persons younger than 60 years.”

� “… no compelling reason to change the current recommendations.”

JAMA. 2014;311(5):507-520.

(SOMEWHAT) SUPPORTING EVIDENCE: HOT

Assess the optimum target diastolic blood pressure in patients with baseline DBP of 100-115 mmHg (ages 50-80 years)� <90 mmHg

� <85 mmHg

� <80 mmHg

Lancet. 1998;351(9198):1755-1762.

RECOMMENDATION 4

In the population aged >18 years with chronic kidney disease, initiate pharmacologic treatment to lower blood pressure at SBP >140 mmHg or DBP >90 mmHg and treat to goal SBP <140 mmHg and goal DBP <90 mmHg.

(Expert Opinion – Grade E)

� Chronic kidney disease:

� Glomerular filtration rate (estimated or measured) <60 mL/min/1.73 m2 in people younger than 70 years of age, OR

� Albuminuria (>30 mg of albumin/g of creatinine at any level of GFR) in people of any age

JAMA. 2014;311(5):507-520.

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Compare the effects of 2 levels of BP control on GFR � Mean arterial pressure goals:

� 102-107 mmHg (usual)

� <92 mmHg (lower)

Primary outcome:� Rate of change in GFR

Clinical composite outcome� Reduction in GFR by 50% or more from baseline

� ERSD

� Death

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

SUPPORTING EVIDENCE: AASKBaseline data

Intervention data

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

SUPPORTING EVIDENCE: AASK

RECOMMENDATION 5

In the population aged >18 years with diabetes, initiate pharmacologic treatment to lower blood pressure at SBP >140 mmHg or DBP >90 mmHg and treat to a goal SBP <140 mmHg and goal DBP <90 mmHg.

(Expert Opinion – Grade E)

JAMA. 2014;311(5):507-520.

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SUPPORTING EVIDENCE: ACCORD BP

Investigate whether therapy targeting normal systolic blood pressure reduces major cardiovascular events in patients with type 2 diabetes � SBP <120 mmHg

� SPB <140 mmHg

Primary outcome:� Composite of nonfatal MI, nonfatal stroke, or

death from cardiovascular causes

N Engl J Med. 2010;362(17):1575-1585.

SUPPORTING EVIDENCE: ACCORD BP

N Engl J Med. 2010;362(17):1575-1585.

NNT to prevent one

stroke over 5 years = 89

SUPPORTING EVIDENCE: ACCORD BP

N Engl J Med. 2010;362(17):1575-1585.

�

��

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(NOT SO) SUPPORTING EVIDENCE: HOT

Assess the optimum target diastolic blood pressure in patients with baseline DBP of 100-115 mmHg (ages 50-80 years)� <90 mmHg

� <85 mmHg

� <80 mmHg

Primary outcome:� Asses the association between major

cardiovascular events and the target blood pressures

� Non-fatal MI, non-fatal stroke, cardiovascular death

Lancet. 1998;351(9198):1755-1762.

(NOT SO) SUPPORTING EVIDENCE: HOT

Lancet. 1998;351(9198):1755-1762.

“…post hoc analysis of a small subgroup (8%) of the

study population that was not prespecified. As a result,

the evidence was graded as low quality.”

Recommendations 1–5:

JAMA. 2014;311(5):507-520.

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RECOMMENDATION 6

In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker, angiotensin-converting enzyme inhibitor, or angiotensin receptor blocker.

(Moderate Recommendation – Grade B)

JAMA. 2014;311(5):507-520.

SO MUCH FOR OTHER COMPELLING INDICATIONS

Thiazide, CCB, ACEI, ARB:� Comparable effects on overall mortality and cardiovascular, cerebrovascular, and kidney outcomes

� One exception – heart failure

Heart failure� Thiazide more effective than a CCB or ACEI, and ACEI more effective than a CCB in improving

outcomes

� Despite this, it still doesn’t get it’s own compelling indication in JNC 8

JAMA. 2014;311(5):507-520.

(heart failure, MI, stroke, high CVD risk)

WHAT ABOUT THE BETA-BLOCKERS

Review of evidence1. Performed similarly to the other drugs in some trials

2. Evidence was insufficient to make a determination in other trials

3. LIFE trial

LIFE trial� Losartan vs. atenolol

� Found a higher incidence of stroke with a beta-blocker than with an ARB

� Losartan n = 232 (5%) vs. atenolol n = 309 (7%), p = 0.001

JAMA. 2014;311(5):507-520.Lancet. 2002;359(9311): 995–1003.

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RECOMMENDATION 7

In the general black population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or calcium channel blocker.

(For black patients without diabetes: Moderate Recommendation – Grade B)

(For black patients with diabetes: Weak Recommendation – Grade C)

JAMA. 2014;311(5):507-520.

SUPPORTING EVIDENCE: ALLHAT

Evidence for this population came from a prespecified subgroup in the ALLHAT trial� ACEI (lisinopril) vs. CCB (amlodipine) vs. thiazide (chlorthalidone)

JAMA. 2002;288(23):2981-2997.

RECOMMENDATION 8

In the population aged >18 years with chronic kidney disease (CKD), initial (or add-on) antihypertensive treatment should include an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status.

(Moderate Recommendation – Grade B)

� “Neither ACEIs nor ARBs improved cardiovascular outcomes for CKD patients compared with a β-blocker or CCB.”

JAMA. 2014;311(5):507-520.

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Recommendations 6–8:

JAMA. 2014;311(5):507-520.

RECOMMENDATION 9

The main objective of hypertension treatment is to attain and maintain goal blood pressure. 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 recommendation 6 (thiazide-type diuretic, CCB, ACEI, or ARB). The clinician should continue to assess BP and adjust the treatment regimen until goal BP is reached. If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list provided. Do not use an ACEI and an ARB together in the same patient. If goal BP cannot be reached using only the drugs in recommendation 6 because of a contraindication or the need to use more than 3 drugs to reach goal BP, antihypertensive drugs from other classes can be used. Referral to a hypertension specialist may be indicated for patients in whom goal BP cannot be attained using the above strategy or for the management of complicated patients for whom additional clinical consultation is needed.

(Expert Opinion – Grade E)

JAMA. 2014;311(5):507-520.

Recommendation 9:

JAMA. 2014;311(5):507-520.

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Journal of Hypertension. 2013;31:1281-1357.

SEEMS SIMPLE ENOUGH

Population JNC 8

2014

ESH/ESC

2013

CHEP

2013

ADA

2013

KDIGO 2012 NICE

2011

General >60 y <150/90 <150/90(>80, <80 y)

<150/90(>80 y)

X X <150/90(>80 y)

General <60 y <140/90 <140/90(nonelderly)

<140/90(<80 y)

X X <140/90(<80 y)

Diabetes <140/90 <140/85 <130/80 <140/80 X X

CKD <140/90 <140/90(CKD with noproteinuria)<130/90CDK with

proteinuria)

<140/90 <140/90(CKD with noproteinuria)<130/90CDK with

proteinuria)

X

OR NOT…

JAMA. 2014;311(5):507-520.