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3/18/2014
HYPERTENSION: Comparison
of New Guidelines
L. Brian Cross, PharmD, BCACP, CDE
Vice-Chair & Associate Professor
Bill Gatton College of Pharmacy
Department of Pharmacy Practice
Associate Professor
James H. Quillen College of Medicine
Department of Family Medicine
Objectives
At the conclusion of the session, participants should be
able to:
 Compare and contrast the 2013 ESH/ESC
Hypertension Guidelines and the 2014 JNC8
Hypertension guidelines
 Understand the background data and development
of the ESH/ESC and JNC8 guidelines
 Apply the recommendations to patient cases
Impact of Hypertension
74.9% are
treated
81.5% of
patients
aware of
diagnosis
52.5% are
controlled
National Health and Nutrition Evaluation Survey 2007-2010.
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Evidence Timeline
ACCOMPLISH
PEACE
ESH/ESC
HYVET
AHA
CAMELOT
EUROPA
ACCF/AHA
ALTITUDE
DREAM NAVIGATOR
2004 2005
2006
ESH/ESC
NICE
REIN-2
JNC 7
2003
ASTRONAUT
ONTARGET ACCORD-BP
ACTION
2007
2008 2009 2010
FEVER
JNC 8
2011 2012 2013
2014
JNC7 vs JNC8
JNC 8 Report. JAMA 2013
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Background/Development JNC8
 Published 12/18/2013 in JAMA
 Evidence limited to RCTs only
 3 Clinical Questions:
1
Does initiating antihypertensive therapy at a specific BP
threshold improve outcomes?
2
Does treatment with antihypertensive therapy to a specific
BP goal lead to improved outcomes?
3
Do various antihypertensive drugs or drug classes differ in
comparative benefits and harms on specific outcomes?
JNC 8 Report. JAMA 2013
Overview of JNC8 Recommendations
Recommendation
Overview
of JNC8
Clinical Question Grade
Key Trials
1
For pts >60 yo: Start tx at >150/90 with a
goal of <150/90
1,2
A
HYVET, Syst-Eur, SHEP,
JATOS, VALISH, CARDIOSIS
2
For pts <60yo: start tx at >90 DBP and treat
to goal of <90 DBP
1,2
A (30-59y0)
E (18-29y0)
HDFP, HTN-Stroke
Cooperative, MRC, ANBP,
VA Cooperative
3
For pts <60 yo: start tx at >140 SBP and
treat to goal of <140 SBP
1,2
E
Expert Opinion
4
In pts >18yo with CKD, start tx at >140/90
and treat to goal of <140/90
2
E
Expert Opinion, AASK,
MDRD, REIN-2
5
For pts >18 yo with diabetes, start tx at
>140/90 and treat to goal of <140/90
2
E
SHEP, Syst-Eur, UKPDS,
ACCORD-BP, Expert
Opinion
6
In nonblack (including diabetic) pts, initial
tx should be a thiazide type diuretic, CCB,
ACEI or ARB
3
B
VA Cooperative, HDFP,
SHEP
7
In black pts (including those with diabetes),
initial therapy should include a thiazide or
CCB
3
B (non-DM)
C (DM pts)
ALLHAT
8
For pts >18yo with CKD and hypertension,
initial (or add on) tx should include an ACEI
or ARB (regardless or race of DM status)
3
B
AASK
9
If goal not reached in 1 month, increase dose
or add 2nd drug (CCB, thiazide, ACE or ARB)
None
E
Expert Opinion
ACCORD-BP
 Intensive (SBP <120) vs. Standard (SBP <140)
 Randomized, open-label, multi-center trial
 4,733 patients with hypertension, stable T2DM and high CV
risk



If established clinical CVD, 40-79 years of age
If ≥ 2 CV risks or subclinical CVD, 55-79 years of age
Achieved BP ~ 119/67 vs. 134/73
N Engl J Med 2010; 362:1575-85.
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ACCORD-BP: Efficacy
N Engl J Med 2010; 362:1575-85.
ACCORD-BP: Safety
N Engl J Med 2010; 362:1575-85.
HOT Trial
Major Cardiovascular Events After 4 Years
Hansson L, et al. Lancet 1998;351:1755-1762.
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Elderly
 2009 Critical analysis of designed trials
 Baselines mostly >160, treatment rarely attaining <140
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013.
Zanchetti A, et al. J Hypertens 2009; 27: 923-334.
Overview of JNC8 Recommendations
Recommendation
Overview
of JNC8
Clinical Question Grade
Key Trials
1
For pts >60 yo: Start tx at >150/90 with a
goal of <150/90
1,2
A
HYVET, Syst-Eur, SHEP,
JATOS, VALISH, CARDIOSIS
2
For pts <60yo: start tx at >90 DBP and treat
to goal of <90 DBP
1,2
A (30-59y0)
E (18-29y0)
HDFP, HTN-Stroke
Cooperative, MRC, ANBP,
VA Cooperative
3
For pts <60 yo: start tx at >140 SBP and
treat to goal of <140 SBP
1,2
E
Expert Opinion
4
In pts >18yo with CKD, start tx at >140/90
and treat to goal of <140/90
2
E
Expert Opinion, AASK,
MDRD, REIN-2
5
For pts >18 yo with diabetes, start tx at
>140/90 and treat to goal of <140/90
2
E
SHEP, Syst-Eur, UKPDS,
ACCORD-BP, Expert
Opinion
6
In nonblack (including diabetic) pts, initial
tx should be a thiazide type diuretic, CCB,
ACEI or ARB
3
B
VA Cooperative, HDFP,
SHEP
7
In black pts (including those with diabetes),
initial therapy should include a thiazide or
CCB
3
B (non-DM)
C (DM pts)
ALLHAT
8
For pts >18yo with CKD and hypertension,
initial (or add on) tx should include an ACEI
or ARB (regardless or race of DM status)
3
B
AASK
9
If goal not reached in 1 month, increase dose
or add 2nd drug (CCB, thiazide, ACE or ARB)
None
E
Expert Opinion
Lots of Options for First Line Therapy…
 2008 ACCOMPLISH


CV event reduction
 ACEi+CCB > ACEi+Thiazide with similar BP lowering
More later…
 2011 NICE Guidelines

“Limited evidence for conferred benefit of initial therapy with low
dose thiazide [comparatively]”
 2013 ESH/ESC Guidelines

“Older guidance (thiazides preferred/only 1st line) NOT supported
by a more extensive review of evidence”
Dorsch M, et al. Hypertension 2011; 57: 689-694.
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013.
National Institute for Health and Clinical Excellence. Hypertension (CG127).
N Engl J Med 2008; 359: 2417-28.
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…except Beta-blockers
 2007 Cochrane Collaboration
 13 RCTs (91,561 patients)
Comparator
CV Disease
Relative Risk (95% CI)
Stroke
Death
Placebo
0.88 (0.79-0.97) 0.80 (0.66-0.96)
0.99 (0.88-1.11)
Thiazide
1.13 (0.99-1.13)
1.17 (0.65-2.09)
1.04 (0.91-1.19)
ACEi/ARB
1.0 (0.72-1.38)
1.3 (1.11-1.53)
1.1 (0.98-1.24)
CCB
1.18 (1.08-1.29)
1.24 (1.11-1.4)
1.07 (1.0-1.14)
Cochrane Database of Systematic Reviews. 2007, Issue 1. Art No.: CD002003:
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013.
Saseen J. Good Things Come to Those Who Wait? ASHP 2012 Presentation.
…and in African Americans
 JNC 8 specific considerations
 ALLHAT subgroup analyses
Cerebrovascular, HF, and CV outcomes
 Thiazide diuretic > ACEi
 Stroke
 ACEi 51% higher rate than CCB
 All outcomes except HF prevention
 Thiazide diuretic = CCB

However,
must consider
CKD
Arch Intern Med 2008; 168(2): 207-217.
JNC 8 Report. JAMA 2013.
For Diabetes…

2008 DREAM & 2010 NAVIGATOR

No significant improvement
Diabetes Care 2008; 31: 1007-1014..
N Engl J Med 2010; 362: 1477-1490.
JNC 7 Report. JAMA 2013
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“Thiazide” means HCTZ, right?
 HCTZ effect on Morbidity/Mortality
 VA Cooperative: HCTZ 100mg + reserpine
 MRC: HCTZ 25-50mg + amiloride
 EWPHE: HCTZ + triamterene
 ANBP2: HCTZ dose not specified
 Chlorthalidone
 SHEP, ALLHAT
 Indapamide
 HYVET
 MRFIT
 ACCOMPLISH
Messerli et al. Am J Med. 2011;124:896-899
JNC8 Algorithm- Initial Therapy
JNC 8 Report. JAMA 2013
JNC8 Algorithm- Add On Therapy
JNC 8 Report. JAMA 2013
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ESH/ESC Guidelines: Risk Assessment
ESH/ESC Guidelines
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013
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3/18/2014
ESH/ESC Guidelines
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013
Treatment With Compelling Indications
JNC 7
ESH/ESC
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013.
JNC 7 Report. JAMA 2003.
Beta Blockers as First Line Therapy?
 Cochrane meta analysis: Beta-blockers may be
inferior to some, but not all, other drug classes for
some outcomes



Total mortality and CV events: BB < CCB
Stroke: BB < CCB and RAS blockers
CHD: BB = CCB, RAS blockers and diuretics
 Law et al.
 Effective in post MI and CHF
 Equal to other classes in preventing coronary outcomes
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013.
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ESH/ESC Guidelines
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013
ESH/ESC Guidelines
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013
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Highlighted Treatment Goal Updates
Parameter
JNC 7
ESH/ESC
JNC 8
CKD
<130/80
<140/90
<140/90
Diabetes
<130/80
<140/80-85
<140/90
<140/90
“fit <140/90,
nonfit <150/90”
<150/90*
Elderly
*Achieving <140/90 is acceptable barring tolerability
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013.
JNC 7 Report. JAMA 2003.
JNC 8 Report. JAMA 2013.
Treatment Without
Compelling Indications
Drug Class
ESH/ESC
JNC 8
ACE inhibitor
✓
✓ non-blacks
✗ blacks
ARB
✓
✓ non-blacks
✗blacks
BB
?
✗
CCB
✓
✓
Thiazide diuretic
✓
✓
ESH/ESC Guidelines for arterial hypertension. Eur Heart J 2013.
JNC 8 Report. JAMA 2013.
JNC8 vs ESH/ESC
JNC 8 Report. JAMA 2013.
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Controversy and Discord
 29% of JNC-8 writers
dissented
 Did they get the
thresholds right?
 Performance Measures
 Patient Education
Cases
 SP is a 54 yo WM who presents to your clinic for a
primary care appointment. His BP today is 164/90,
taken appropriately. At his last visit 3 months ago,
his BP was 156/88, also taken appropriately. SP
does not monitor his BP at home. Upon
questioning, you find that he does not smoke, has
not had any caffeine today, and took all of his
morning medications. He has no complaints and is
feeling well today. He has a history of T2DM,
Dyslipidemia, COPD, allergic rhinitis, esophageal
reflux, and osteoarthritis.
What is SP’s blood pressure goal?
A. <130/80
B. <140/80
C. <140/90
D. <140/85
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What medication, if any, would you initiate for
SP’s blood pressure?
A. Therapeutic lifestyle
changes and lisinopril
10mg daily
B. Therapeutic lifestyle
changes and HCTZ
25mg daily
C. Therapeutic lifestyle
changes and re-evaluate
in 4 weeks for the need
to add medication
D. Therapeutic lifestyle
changes and metoprolol
tartrate 25mg BID
How might your management change if SP were
a 54yo AAM?
A. Initiate therapy with
lisinopril/HCTZ
rather than lisinopril
alone
B. Initiate therapy with
HCTZ alone
C. Initiate therapy with
amlodipine alone
D. Initiate therapy with
HCTZ and amlodipine
How would your management change if SP’s Scr
were 2.9 (est Crcl = 28 ml/min)?
A. BP goal would change
to <130/80
B. Change HCTZ to
furosemide
C. Discontinue lisinopril
D. Continue current
management as all
doses are appropriate
for current renal
function
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3/18/2014
References

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Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guideline for the management of arterial hypertension. J Hypertens.
2013; 31:1281-1357.
James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guidlelines for the management of high blood pressure in adults: Report
From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2013;. doi:10.1001/jama
2013.284427.
Wright JT Jr, Bakris G, Greene T, et al. Effect of blood pressure lowering and antihypertensive drug classon progression of
hypertensive kidney disease: results from the AASK trial.; African American Study of Kidney Disease and Hypertension Study
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Yusuf S, Sleight P, Pogue J, et al. The Heart Outcomes Prevention Evaluation (HOPE) Study Investigators, Effects of an
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Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with
hypertension: principal results of the Hypertension Optimal Treatment (HOT)randomised trial. HOT Study Group. Lancet 1998
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References
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Pitt B, Byington RP, Furberg CD, et al. Effect of amlodipine on the progression of atherosclerosis and the
occurrence of clinical events. PREVENT Investigators. Circulation 2000 Sep 26;102(13):1503-10.
Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after
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Angiotensin II Antagonist Losartan.; OPTIMAAL Steering Committee of the OPTIMAAL Study Group. Lancet
2002 Sep 7;360(9335):752-60.
Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in
patients with type 2 diabetes and nephropathy; RENAAL Study Investigators. N Engl J Med
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Tuomilehto J, Rastenyte D, Birkenhager WH, et al. Effects of calcium-channel blockade in older patients with
diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators (Syst-Eur). N Engl J
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Questions?
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