Updates on the Management of Hypertension
A Review of the JNC8 Guidelines
Timothy Gladwell, Pharm.D., BCPS, BCACP
Associate Professor and Vice Chair
Department 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, 2011-2012
Available at http://www.cdc.gov. Accessed 8/24/14.
Hypertension in the U.S.
Source:CDC/NHNS, National Health and Nutrition Examination Survey, 2011-2012
Available at http://www.cdc.gov. Accessed 8/24/14.
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)
< 120
< 80
Pre-hypertension
120-139
80-89
Stage 1 hypertension
140-159
90-99
Stage 2 hypertension
> 160
> 100
Normal
Chobanian AV et al. JAMA 2003;289:2560-72.
JNC-7 Treatment Algorithm
Chobanian AV et al. JAMA 2003;289:2560-72.
JNC-7 Compelling Indications
Chobanian AV et al. JAMA 2003;289:2560-72.
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?]
James PA et al. JAMA 2014;311:507-20.
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
James PA et al. JAMA 2014;311:507-20.
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
James PA et al. JAMA 2014;311:507-20.
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
James PA et al. JAMA 2014;311:507-20.
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
James PA et al. JAMA 2014;311:507-20.
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 reninangiotensin-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 CHD
The 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
James PA et al. JAMA 2014;311:507-20.
Comparisons to Other Guidelines
BP 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 Guidelines
JNC-7
Non-black Thiazide
(no DM or
CKD)
Black (no
DM or
CKD)
Diabetes
CKD
Thiazide
JNC-8
ASH/ISH
Thiazide, <60:ACEI,
ACEI, ARB, ARB
CCB
>60:CCB,
thiazide
Thiazide, Thiazide,
CCB
CCB
ESC/ESH
CHEP
Thiazide, Thiazide,
ACEI, ARB, ACEI, ARB
CCB, BB
(BB if <60)
Thiazide,
ACEI, ARB,
CCB, BB
ACEI, ARB, CCB,
ACEI, ARB, ACEI, ARB
CCB, BB,
thiazide
CCB,
thiazide
thiazide
ACEI, ARB ACEI, ARB ACEI, ARB ACEI, ARB
Adapted from Salvo M et al. Ann Pharmacother 2014;48:1242-8.
Thiazide,
ARB (BB if
<60)
ACEI, ARB,
CCB,
thiazide
ACEI, ARB
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 #1
Changes 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 #2
JF 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. Lisinopril
2. Chlorthalidone
3. Atenolol
4. Valsartan
Post-Lecture Question #3
According to the JNC8 guidelines, the goal blood
pressure for an adult patient with diabetes
mellitus is:
1. <120/80
2. <130/80
3. <140/90
4. <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-withoutcompelling-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.
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.