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• I, however, have to rely, post-hoc, on a published “minority report,” “opinion,” “commentaries,” “editorials,” and unpublished data to present the “Contrary” point of view, so I am at a distinct disadvantage.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