2014 Evidence-Based

Guidelines for the

Management of High Blood

Pressure: Did They Get It

Right? (CON)

William J. Elliott, M.D., Ph.D.

Pacific Northwest University of Health Sciences,

Yakima, WA

DISCLOSURE OF RELATIONSHIPS

For William J. Elliott over the past 12 months,

Grant/Research Support: None.

Consultant: None.

Speakers Bureau: None.

Stock shareholder: None! I once worked at RUSH!!

Other Support, Tangible or Intangible:

Elsevier (Division of Harcourt); UpToDate®

Affidavit of Originality

• The following material is based exclusively on the

speaker’s own opinion, knowledge and expertise.

• There is no organization, company, or entity that

has exercised any control or influence over the

content of this presentation, nor has any other

person or organization had any part in drafting,

scripting or designing its content.

• The information presented is based on the

principles of “Evidence-Based Medicine,” and is

intended to avoid promotion of any specific

commercial interest, product, or company.

Disclaimer

• The speaker asserts that all views expressed are likely more extreme than those he would personally espouse, and are presented in this manner for their entertainment value, in the spirit of academic debate and discussion.

• My worthy and esteemed opponent in this debate is a good friend and colleague, and had the full power and credit of the US Federal Government behind him (and his co-authors) when JNC 8 was begun.

• I, however, have to rely, post-hoc, on a published “minority report,” “opinion,” “commentaries,” “editorials,” and unpublished data to present the “Contrary” point of view, so I am at a distinct disadvantage.

My Grandfather Once Said:

“It is a POOR

workman who blames

his tools, or the

conditions under

which he labors…”

How

“Evidence-Based”

Were These

Guidelines?

Report Card: JNC 8 Recommendations

Grade of Evidence # of Recommendations

A 1

B 2.5

C 0.5

D 0

E 5

JAMA. 2014;311:507-520

JNC 8’s “Evidence-Based

Guidelines” Report Card

1

2.5

0.5

0

5

A B C D E0

1

2

3

4

5

Grade of Evidence

Nu

mb

er

of

Reco

mm

en

dati

on

s

JAMA. 2014;311:507-520

GPA = 1.38

How Does JNC 8

“Measure Up” to the

Proposed “Guidelines

for Guidelines” by

Lenzer et al.?

BMJ (Clin Res). 2013;347:f5535

“Red Flags” for Potential Bias

in Guidelines Committee chair and co-chairs have financial

conflicts?

Yes

Multiple panel members with financial conflicts? Yes

Any professional conflicts? Yes

Exclude minority views in the main report? Yes

No/limited involvement of experts in research

methodology?

Yes

No external reviews? No

No patient representative/community stakeholders? Yes

Am J Hypertens. 2014;27:1444

JNC 8: Recommendation 1 • In the general population aged 60 years or

older, initiate pharmacologic treatment to

lower blood pressure at systolic blood

pressure (SBP) of 150 mm Hg or higher, or

diastolic blood pressure (DBP) of 90 mm Hg

or higher, and treat to a goal SBP lower than

150 mm Hg and a goal DBP lower than 90

mm Hg.

– Strong recommendation: Grade A.

– (Editorial Comment: Never before had a JNC

recommended a SBP target > 140 mm Hg!) JAMA. 2014;311:507-520

JNC 8: Recommendation 1 • This proved to be the most controversial of all the

JNC 8 recommendations; a minority of its members supported maintaining the traditional SBP target of < 140 mm Hg (as have all other guidelines for people < 80 years of age).

• JNC 8 Corollary Recommendation: In the general population aged 60 years or older, if pharmacologic treatment for high blood pressure results in lower achieved SBP (for example, < 140 mm Hg) 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.

Ann Intern Med. 2014;160:499-503; JAMA. 2014;311:507-520

HTN Trials in Older Adults • SHEP (not goal-directed)

• Syst-Eur (European, not goal-directed)

• Syst-China (not randomized, Chinese)

• FEVER (Chinese, not goal-directed)

• HYVET (open-label, not done in USA)

• JATOS (Japanese, underpowered?)

• Cardio-Sis (open-label, < 130 v. < 140)

• VALISH (Japanese, underpowered?)

Adapted from Am J Med Sci. 2014;348:131

SHEP: Strokes by In-Trial SBP n=4736; baseline BP = 170/77; goal SBP < 160, or ≥ 20 drop

JAMA. 2000;284:469 Relative Risk of Stroke with Given SBP

< 140

< 150

< 160

0.4 1

RR = 0.62 (0.47-0.82)

**

RR = 0.78 (0.57-1.07) n = 1356

SBPRR = 0.67 (0.51-0.89)

n = 3162

n = 2335

FEVER: Post-hoc Analysis

• 9711 Chinese patients 50-79 (mean: 61) years

old, with baseline BP 159/93 mm Hg, received

HCTZ 12.5 mg/d, and then were randomized to

placebo or felodipine 5 mg/d, and followed for 40

months for stroke (the 1° endpoint).

• Achieved BPs were 142 (HCTZ) and 138

(felodipine + HCTZ) mm Hg.

• Stroke was significantly reduced in those with

average SBP < 140 mm Hg (by 39%), and in all

subgroups (including those > 65 years, 44%).

J Hypertens. 2005;23:2157-72; Eur Heart J. 2011; 32:1500-8

INVEST: Post-hoc Analysis • 8354 > 60 year olds with CAD and HBP, followed for

2.7 years, with in-trial SBPs < 140 or 140-9 mm Hg.

1° Outcome Death CV Death MI Stroke

1.01.09

(0.93-1.29)

P = 0.27

1.00 (0.83-1.20)

P = 0.99

1.31 (1.00-1.73)

P = 0.05

1.14 (0.87-1.51)

P = 0.34

1.88 (1.27-2.78)

P = 0.002

3.0

HR

(S

BP

< 1

40 v

s. 140

-9 m

m H

g)

JACC. 2014;64:784-93

HTN Trials in Older Adults • SHEP (not goal-directed)

• Syst-Eur (European, not goal-directed)

• Syst-China (not randomized, Chinese)

• FEVER (Chinese, not goal-directed)

• HYVET (open-label, not done in USA)

• JATOS (Japanese, underpowered?)

• Cardio-Sis (open-label, < 130 v. < 140)

• VALISH (Japanese, underpowered?)

Adapted from Am J Med Sci. 2014;348:131

FEVER, JATOS & VALISH

J Hypertens. 2005;23:2157; Hypertens Res. 2008:31:2115; HTN. 2010;56:196

SBP < 140 140-149

Stroke 245/8598 323/8610

MACE 349/8598 457/8610

MI 102/8598 131/8610

Death 190/8598 223/8610

CV Death 93/8598 119/8610

HF 26/7053 34/7076

0.5 1 Odds Ratio

• In the population aged 18 years or older with chronic kidney disease (CKD), initiate pharmacologic treatment to lower blood pressure at SBP of 140 mm Hg or higher, and treat to a goal SBP of lower than 140 mm Hg. – Expert Opinion—Grade E.

• In the population aged 18 years or older with diabetes, initiate pharmacologic treatment to lower blood pressure at SBP of 140 mm Hg or higher, and treat to a goal SBP of lower than 140 mm Hg. – Expert Opinion—Grade E.

JNC 8: Recommendations 4 &5

JAMA. 2014;311:507-520; Ann Intern Med. 2013;158:825-830

Major CV Events: HOT Diabetics

n = 499

MI,

Str

oke o

r C

V D

eath

(/1

000 p

t-yrs

)

n = 501 n = 501

< 80 < 85 < 90 0

5

10

15

20

25

Target Diastolic BP (mm Hg)

P = 0.005

Lancet . 1998; 351 :1755

51%

Pa

tie

nts

wit

h E

ve

nts

(%

)

0

5

10

15

20

Years Post-Randomization

0 1 2 3 4 5 6 7 8

Pati

en

ts w

ith

Even

ts (

%)

0

5

10

15

20

Years Post-Randomization

0 1 2 3 4 5 6 7 8

Nonfatal Stroke Total Stroke

HR = 0.63

95% CI (0.41-0.96) HR = 0.59

95% CI (0.39-0.89)

(p=0.01) (p=0.03).

N Engl J Med. 2010;362:1575-85

ACCORD: 2° Endpoint

Who Is At Risk for Stroke?

• Older Americans

• Blacks

• Women

• Diabetics

• Those with chronic kidney disease

• These groups are likely to be negatively impacted by the more permissive BP targets of JNC 8.

JACC. 2014;64:394-402

Stroke Deaths, USA

• 1908-1953: #2 Cause of Death

• 1954-2004: #3 Cause of Death

• 2005-2012: #4 Cause of Death

• 2013: #5 Cause of Death

NCHS Data Brief. 2014:178, table 1

BP Control & Stroke Deaths

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

4.9

5.4

5.9

6.4

6.9

50

40

30

20 % o

f D

ea

ths D

ue t

o S

tro

ke

% o

f P

eo

ple

wit

h B

P <

140

/90

Year (A.D. or C.E.)

BP Control & Stroke Deaths

% with BP < 140/90 in NHANES

% o

f D

eath

s D

ue t

o S

tro

ke

Cost-Effectiveness: HTN Rx

• The Cardiovascular Disease Policy Model (a

Monte Carlo computer simulation) was used to

estimate the costs, outcomes, and cost-

effectiveness of hypertension treatment among

35-74 year old Americans, using JNC 8

treatment algorithms.

• Full implementation of JNC 8 guidelines would

prevent 56,000 cardiovascular events, 13,000

deaths, and be cost-saving overall.

N Engl J Med. 2015;372:447-55

Cost-Effectiveness: HTN Rx

• Using a simpler computer model (citation

below), treating all American adults > 60

years of age to a BP target of < 140/90 mm

Hg (rather than < 150/90 mm Hg) should:

• Prevent ~11,000 more strokes

• Prevent ~5,000 more myocardial infarctions

• Prevent ~3,000 more deaths

• and still be cost-saving overall.

Arch Intern Med. 2000;160:1277-83

Conclusions

• The “2014 Evidence-Based Guidelines for the

Management of High Blood Pressure”

– Are mostly NOT “Evidence-Based.”

– Raise “red flags” about potential conflicts.

– “Improve” national statistics about BP control (by

widening the goalposts).

– Are a “clear and present danger” that increase the

risk of stroke in Americans who are older, black,

female, diabetic, or have chronic kidney disease.

– Result from NOT considering the “totality of the

evidence,” as is traditional in civil cases.