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Updates on the Management of Hypertension

A Review of the JNC8 Guidelines

Timothy Gladwell, Pharm.D., BCPS, BCACPAssociate Professor and Vice ChairDepartment of Pharmacy Practice

Husson University School of Pharmacy

Faculty Disclosure

Tim Gladwell, PharmD, BCPS, BCACP does not have any actual or potential conflicts of

interest in relation to this CE activity.

Learning Objectives• At the conclusion of this session, participants should

be able to:– Review the current status on the epidemiology,

diagnosis, and treatment of hypertension in the US– Discuss major differences between JNC7 and JNC8– Reconcile the differences in treatment

recommendations among the most recently published guidelines for the management of hypertension

– Apply an evidence-based approach to the management of patients with hypertension

Hypertension in the U.S.

Source:CDC/NHNS, National Health and Nutrition Examination Survey, 2011-2012Available at http://www.cdc.gov. Accessed 8/24/14.

http://www.cdc.gov/

Joint National Committee (JNC)• Panel appointed by the

National Heart, Lung, and Blood Institute (NHLBI)

• First guidelines (JNC-1) published in 1977

• Subsequent updates published in 3- to 6-year intervals

• Last edition (JNC-7) published in 2003

Chobanian AV et al. JAMA 2003;289:2560-72.

JNC-7 Blood Pressure Classification

Blood Pressure Classification

Systolic blood pressure(mm Hg)

Diastolic blood pressure(mm Hg)

Normal < 120 < 80

Pre-hypertension 120-139 80-89

Stage 1 hypertension 140-159 90-99

Stage 2 hypertension > 160 > 100


JNC-7 Treatment Algorithm


JNC-7 Compelling Indications


Development of JNC-8• Commissioned by the NHLBI in 2008– Panel members appointed– Developed focused critical questions relevant to practice– Conducted a systematic search of pertinent literature• Limited to randomized controlled trials (RCTs) published

between 1966 and 2009• Included patients age 18 or older with hypertension• Sample size of 100 patients or more• Results must have included “hard” outcomes• Subsequent search of studies from 2009 to 2013 required

samples of 2000 or more patients

James PA et al. JAMA 2014;311:507-20.

Development of JNC-8• 3 critical questions for adults with hypertension– Does initiating antihypertensive pharmacologic

therapy at specific blood pressure thresholds improve health outcomes? [When to start therapy?]

– Does treatment with antihypertensive pharmacologic therapy to a specified blood pressure goal lead to improvements in health outcomes? [How low should I go?]

– Do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? [What drug do I use?]


Development of JNC-8

And then we wait…and wait…

Development of JNC-8• In 2013, the NHLBI decides that it will no

longer publish clinical guidelines– Proposes to work collaboratively with other

organizations• The appointed panel members for JNC-8

decided to publish their findings independently– Published online in JAMA in December 2013– Received no endorsements from other organizations


But Wait…There’s More• A multitude of other hypertension guidelines

were also published in 2013:– AHA/ACC/CDC advisory algorithm– American Society of Hypertension/International

Society of Hypertension (ASH/ISH)– European Society of Hypertension and European

Society of Cardiology (ESH/ESC)– Canadian Hypertension Education Program

(CHEP)

JNC-8 Recommendations• In patients >60 years of age, start medications at

blood pressure of >150/90mm Hg and treat to goal of <150/90mm Hg

• In patients >60 years of age, treatment does not need to be adjusted if achieved blood pressure is lower than goal and well-tolerated


Hypertension in the Elderly• Fastest growing segment of the population• Prevalence of hypertension is very high• Several issues make managing HTN unique:– Often present with isolated systolic HTN–More likely to present with comorbidities–Many clinical trials in HTN have excluded these

patients (particularly for those 80 years and older)– Elderly are more susceptible to certain adverse

effects (orthostatic hypotension)

HYVET• HYpertension in the Very Elderly Trial– Randomized, double-blind trial– Included patients aged 80 or older with

SBP>160mmHg– Randomized to indapamide +/- perindopril or

placebo– Target BP of 150/80mmHg– Primary outcome of fatal or nonfatal stroke

Beckett NS et al. N Engl J Med 2008;358:1887-98.

HYVET• Results–Mean BP at the end of the trial• Indapamide +/- perindopril - 143/78 mm Hg• Placebo – 158/84 mm Hg

– 48.0% of indapamide patients achieved goal BP vs. 19.9% of placebo patients (p<0.001)

– Outcomes with indapamide +/- perindopril• 30% reduction in stroke (p=0.06)• 64% reduction in heart failure (p<0.001)• 21% reduction in all-cause mortality (p=0.02)

Beckett NS et al. N Engl J Med 2008;358:1887-98.

Hypertension in the Elderly• HYVET demonstrated that treatment of HTN

to goal BP less than 150/80 mm Hg in patients >80 years old was safe and effective

• But…what about a lower BP goal?

• And…what about the patients age 60-80?

Hypertension in the Elderly• Two “treat-to-target” trials in this age group– Japanese Trial to Assess Optimal SBP (JATOS)

• 4416 patients aged 65-85 (average age of 74)• Randomized to SBP<140 vs. SBP 140-160• Achieved BP of 136/75 vs. 146/78• No difference in CV events or renal failure (p=0.99)

– VALISH trial• 3079 patients aged 70-84 (average age of 76)• Randomized to SBP<140 or SBP 140-149• No significant reductions in stroke, CV events, or renal failure

– Overall event rates were lower than anticipated in both of these studies

JATOS Study Group. Hypertens Res 2008;31:2115-27.Ogihara T et al. Hypertension 2010;56:196-202.

Hypertension in the Elderly

• Dissension among the ranks!

Wright JT Jr et al. Ann Intern Med 2014;160:499-504.

Hypertension in the Elderly• The opposing arguments:– The Japanese trials had low event rates and may not

represent the risks in other populations– Data from other studies suggests a goal SBP closer to

140mm Hg may be more appropriate for ages 60-80• Methodology may have prevented JNC-8 panel from

considering the results in their analysis– The “Speed Limit” effect

Wright JT Jr et al. Ann Intern Med 2014;160:499-504.

JNC-8 Recommendations• In patients <60 years of age, start medications at

blood pressure of >140/90mm Hg and treat to goal of <140/90mm Hg

• In all adult patients with diabetes or chronic kidney disease, start medications at blood pressure of >140/90mm Hg and treat to goal of <140/90mm Hg


Hypertension in Diabetics• Action to Control CV Risk in Diabetes (ACCORD)– Randomized, double-blind trial– Included patients with T2DM and high CV risk– Randomized to SBP<120 or SBP<140– Primary outcome of CV death, MI, or stroke– Results• Mean SBP of 119 mm Hg vs. 133 mm Hg• No significant difference in primary outcome (HR=0.88,

p=0.2)• Incidence of stroke was lower with intensive treatment

(HR 0.59, p=0.01)• Significant increase in serious adverse events

The ACCORD Study Group. N Engl J Med 2010;362:1575-85.

JNC-8 Recommendations• For the non-black population (including

diabetes), initial antihypertensive treatment may include a thiazide, ACEI, ARB, or CCB

• For the black population (including diabetes), initial antihypertensive treatment should include a thiazide or CCB

• For all patients with CKD, initial (or add-on) therapy for hypertension should include an ACEI or ARB


Initial Drug Selection for HTN• ALLHAT– Randomized, double-blind trial– Enrolled 33,357 patients age 55 or older• Chlorthalidone• Amlodipine• Lisinopril• Doxazosin (this arm stopped early 2° worse outcomes)

– Primary outcome of CHD death or nonfatal MI– No significant difference in primary outcome among

the thiazide, ACEI, or CCB

The ALLHAT Collaborative Research Group. JAMA 2002;288:2981-97.

Initial Drug Selection for HTN• African-American patients– High risk for CV events– Less responsive to drugs that act on the renin-

angiotensin-aldosterone system• ACEI, ARB, BB

– Subgroup analysis of black patients in ALLHAT• Less BP reduction with lisinopril than amlodipine• Risk of stroke was significantly higher with lisinopril than

with amlopdipine (RR 1.51, 95% CI 1.22-1.86)• Lisinopril less effective than chlorthalidone in preventing

heart failure, stroke, and combined CHDThe ALLHAT Collaborative Research Group. JAMA 2002;288:2981-97.

Initial Drug Selection for HTN• What happened to the beta-blockers (BB)?– Most evidence for BB is from atenolol

• Does not meet current FDA criteria for a once-daily drug– Losartan Intervention for Endpoint reduction (LIFE)

study• Compared losartan vs. atenolol in pts. with HTN & LVH• Primary outcome of CV death, MI, or stroke• Overall 13% RRR with losartan vs. atenolol (p=0.021)• Driven mainly by 25% reduction in risk of stroke (p=0.001)

• BB still recommended for many patients with comorbid conditions (CHF, CAD, etc.)

Dahloff B et al. Lancet 2002;359:995-1003.

JNC-8 Recommendations• Initiate therapy according to recommendations• If BP is not at goal in one month, increase dose or

add a second agent from recommended classes• If patient is still not at goal, add a third drug from

recommended classes– Do not use an ACEI and ARB together

• Drugs from other classes may be used if additional BP lowering is needed or if contraindications exist

• Refer to HTN specialist whenever necessary


Comparisons to Other GuidelinesBP Goal JNC-7 JNC-8 ASH/ISH ESC/ESH CHEP

Age < 60 <140/90 <140/90 <140/90 <140/90 <140/90

Age 60-79 <140/90 <150/90 <140/90 <140/90 <140/90

Age 80+ <140/90 <150/90 <150/90 <150/90 <150/90

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

CKD <130/80 <140/90 <140/90 <130/90 <140/90

Adapted from Salvo M et al. Ann Pharmacother 2014;48:1242-8.

Comparisons to Other GuidelinesJNC-7 JNC-8 ASH/ISH ESC/ESH CHEP

Non-black (no DM or CKD)

Thiazide Thiazide, ACEI, ARB, CCB

<60:ACEI,ARB>60:CCB, thiazide

Thiazide, ACEI, ARB, CCB, BB

Thiazide, ACEI, ARB (BB if <60)

Black (no DM or CKD)

Thiazide Thiazide, CCB

Thiazide, CCB

Thiazide, ACEI, ARB, CCB, BB

Thiazide, ARB (BB if <60)

Diabetes ACEI, ARB, CCB, BB, thiazide

CCB, thiazide

ACEI, ARB, CCB, thiazide

ACEI, ARB ACEI, ARB, CCB, thiazide

CKD ACEI, ARB ACEI, ARB ACEI, ARB ACEI, ARB ACEI, ARB

Adapted from Salvo M et al. Ann Pharmacother 2014;48:1242-8.

Patient Case – Mr. Jackson• 62-y/o African-American man• PMH includes T2DM and dyslipidemia• BP at previous office visit was 146/94• Today’s BP is 144/92• Current medications– Aspirin 81mg daily–Metformin 500mg twice daily– Atorvastatin 40mg daily

• Labs WNL except for A1c 7.2%

Does Mr. Jackson need treatment for HTN?

Patient Case – Mr. Jackson• According to JNC-7:– Goal BP for a diabetic patient was <130/80

• According to JNC-8 (and the ASH/ISH guidelines):– Goal BP for a diabetic patient is <140/90

• Choices of agents include:– Thiazide or CCB?– ACEI or ARB?

Post-Lecture Question #1Changes in the recommendations of the JNC8 guidelines as compared to those in the JNC7 guidelines include:1. Less intensive blood pressure goals for patients 60

years of age or older and those with diabetes or chronic kidney disease

2. Removal of beta-blockers from the list of preferred initial therapies for the management of hypertension in the general population

3. Addition of preferred drug classes for the initial management of hypertension in black patients

4. All of the above

Post-Lecture Question #2JF is a 52-year-old African-American man who has just been diagnosed with hypertension. He has no other comorbidities or contraindications to medications. According to the JNC8 guidelines, which of the following medications would be most appropriate for the initial management of JF’s blood pressure?1. Lisinopril2. Chlorthalidone3. Atenolol4. Valsartan

Post-Lecture Question #3According to the JNC8 guidelines, the goal blood pressure for an adult patient with diabetes mellitus is:1. <120/802. <130/803. <140/904. <150/90

Questions???

References• Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on

Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA 2003;289:2560-2572.

• James PA, Oparil S, Carter BL, et al. 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). JAMA 2014;311:507-520.

• Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens 2014;16:14-26.

• Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension. Eur Heart J 2013;34:2159-2219.

• Hypertension without compelling indications: 2013 CHEP Recommendations. Hypertension Canada Website. https://www.hypertension.ca/en/professional/chep/therapy/hypertension-without-compelling-indications

• Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years or older (HYVET). N Engl J Med 2008;358:1887-1898.

• JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res 2008;31:2115-2127.

https://www.hypertension.ca/en/professional/chep/therapy/hypertension-without-compelling-indications




References• Ogihara T, Saruta T, Rakugi H, et al. Target blood pressure for treatment of isolated systolic

hypertension in the elderly: valsartan in elderly isolated systolic hypertension study (VALISH). Hypertension 2010;56:196-202.

• Wright JT, Fine LJ, Lackland DT, et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med 2014;160:499-503.

• The ACCORD Study Group. Effects of intensive blood pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-85.

• ALLHAT Collaborative Research Group. The antihypertensive and lipid-lowering treatment to prevent heart attack trial: major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic. JAMA 2002;288:2981-2997.

• Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:995-1003.

• Salvo M and White CM. Reconciling multiple hypertension guidelines to promote effective clinical practice. Ann Pharmacother 2014;48:1242-8.

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