Debate evidence bases guideline handler

1. Joel Handler, MD
Southern Cal Kaiser Permanente
Hypertension Lead
Southern California Permanente Group
JNC 8: They Got it Right
Joint NationJlJ COmmittee

2. I
I Have NO
Disclosures

3. Joint National Committee on
Prevention, Detection,
Evaluation, & Treatment of High
Blood Pressure (JNC)
JNC 7: 2003
JNC 6: 1997
JNC 5: 1992
JNC 4: 1988
JNC 3: 1984
JNC 2: 1980
JNC 1: 1976
Detection, Evaluation, &
Treatment of High Blood
Cholesterol in Adults (ATP, Adult
Treatment Panel)
ATP III Update: 2004
ATP III: 2002
ATP II: 1993
ATP I: 1988
Clinical Guidelines on the
Identification, Evaluation, &
Treatment of Overweight and
Obesity in Adults
Obesity 1: 1998
3
History of
NHLBI CVD Adult Clinical Guidelines

4. NHLBI Study Assessment Tool:
Controlled Intervention Studies
Criteria Yes No Other
1.Was the study described as randomized, a randomized trial, a randomized clinical
trial, or an RCT?
5. Were the people assessing the outcomes blinded to the participants’ group
assignments?
7. Was the overall drop-out rate from the study at its endpoint 20% or less than the
number originally allocated to treatment?
14. Were all randomized participants analyzed in the group to which they were
originally assigned (i.e., did they use an intention-to-treat analysis)?
Quality Rating (Good, Fair, Poor) (see guidance)
Rater #1 initials: Rater #2 initials:
Additional Comments (If POOR, please state why):

5. Articles Screened = 1978
Good = 17
Included = 92
Total Abstracted = 56
Excluded = 1886
(Did not meet
prespecified
inclusion criteria)Poor = 36Fair = 39
Question 2: Among adults, does treatment with antihypertensive
pharmacological therapy to a specified BP goal lead to improvements
in health outcomes?

6. NHLBI Systematic Review and
Guideline Development Process
Literature Searched;
All Eligible Studies
Identified
Studies Quality Rated;
Evidence Tables
Developed
Evidence
Summarized;
Graded by Panel
w/ Methodologists
Resources
Obtained;
Expert Panel
Established
Topic Area
Identified
Critical Questions,
Study Eligibility
Criteria Identified
Draft Reports
Written, Reviewed,
Revised
Reports
Disseminated &
Implemented
Recommendations
Developed and Graded
By Panel
*The Blue portion is the Systematic Review

8. In the general adult population 60 years
of age and older, initiate pharmacologic
treatment to lower blood pressure at SBP
≥ 150mm Hg or DBP ≥ 90mm Hg and treat
to a goal SBP <150 mm Hg and goal DBP
<90mmHg.
(Strong Recommendation – Grade A)
Recommendation

9. Corollary : In the general population 60 years
of age and older, if pharmacologic treatment
for high blood pressure results in a lower
achieved SBP (for example, less than 140
mmHg) and treatment is well tolerated without
adverse effects on health or quality of life,
treatment does not need to be adjusted
Expert opinion
Recommendation

10. Major Trials Testing SBP Goals
in General Populations
SHEP Syst-Eur HYVET JATOS VALISH
Number 4,736 4,695 3,845 4,418 3,260
Entry SBP 160-219 160-219 160-199 ≥160 ≥160
Goal SBP <148 <150 <150 <140 <140
Achieved SBP 142 151 144 136 137
Stroke  36% 42% ns ns ns
CVD  32% 31% 34% ns ns
Mortality  ns ns 21% ns
nsSBP = systolic blood pressure
CVD = cardiovascular disease
151

11. JNC 8 Misrepresentation
• JNC 8 did not base it’s SBP 150
recommendation on JATOS and
VALISH
• SHEP, SystEur, and HYVET were
highly rated studies
• Only HYVET randomized age 80
and over

12. Summary Table for Goal BP Question

14. Evidence Quality
Type Of Evidence Quality
Rating
Well-designed, well executed RCTs that adequately
represent populations to which the results are
applied and directly assess effects on health
outcomes
High

16. The absence of
The absence of evidence for
a goal SBP lower than other
than < 150 mmHg does NOT
equal evidence.

17. Why Not Use Achieved Blood
Pressures?
•Mean achieved BPs are not Goal BPs
•Post Hoc Analyses of patients achieving
lower BPs tend to identify those at lower
risk: less LVH, lower baseline BPs, fewer
meds, improved med adherence

19. Cochrane Database of Systematic Reviews:
Treatment Blood Pressure Targets for
Hypertension 2009
“The cohort of patients with low blood
pressure as identified by achieved blood
pressure selects for patients who did not
have sustained elevated blood pressure in
the first place, for patients in whom the blood
pressure is most easily reduced, for patients
with the lowest baseline blood pressure, and
for patients who are most compliant (healthy
user effect, Dormuth 2009).”
continued …

20. Cochrane 2009 continued
“All of these factors are most
likely associated with a lower risk
of having an adverse
cardiovascular event. The
approach is thus heavily biased for
finding less cardiovascular events
in the patients with lower blood
pressure.”
Arguedas JA, Perez MI, Wright JM

21. Which clinical trials + meta-analyses were
excluded because of excessive bias?
• FEVER
• PREVENT
• BP Lowering Treatment
Trialists’ Collaboration

22. Recommendation 1:
In the general adult population 60 years of age and
older, initiate pharmacologic treatment to lower blood
pressure at SBP ≥150 mm Hg or DBP ≥90 mm Hg and
treat to a goal SBP <150 mm Hg and goal DBP <90
mm Hg.
(Strong Recommendation - Grade A)
• Motion voted on during February 27-28 face-to-face
meeting: move forward with recommendation as is,
but include a ‘thoughtful’ discussion of the
epidemiological data and other consideration in the
narrative
• 15 in favor, 2 against

23. EVIDENCE STATEMENTS FOR QUESTION 2 CONTRIBUTING TO RECOMMENDATION 1
Question 2: Among adults, does treatment with antihypertensive pharmacological
therapy to a specified BP goal lead to improvements in health outcomes?
Evidence Statement 1: Treatment with antihypertensive medication to lower SBP in
adults 60 years of age or older to a goal systolic BP <150 mm Hg reduces
cerebrovascular morbidity and mortality (includes fatal stroke, nonfatal stroke or a
combination of fatal and nonfatal stroke).
Vote: Agree with the statement (17/17); Evidence Quality: High (15/17),
Moderate (2/17)
Evidence Statement 2: Treatment with antihypertensive medication to lower
SBP in adults 60 years of age or older to a goal systolic BP <150 mm Hg reduces
fatal and nonfatal heart failure.
Vote: Agree with the statement (17/17); Evidence Quality: Moderate (15/17),
High (2/17)
Evidence Statement 3: Treatment with antihypertensive medication to lower
SBP in adults 60 years of age or older to a goal systolic BP <150 mm Hg
reduces coronary heart disease (includes non-fatal MI, fatal MI, CHD death, or
sudden death).
Vote: Agree with the statement (17/17); Evidence Quality: Moderate (17/17)

26. Will a higher SBP goal facilitate therapeutic
inertia?
“Clinical inertia has to be fought by
other means than by recommending
inappropriately low BP targets.”
Mancia G, Fagard R. J Hypertension
2013; 31: 2462-2465

27. BMJ 2015; 350

29. Why is it important not to recommend intensifying
medication to reduce BP below the level proven in
clinical trials?
• Exposure to side effects of unnecessary
medications and excessive doses
• Polypharmacy in the elderly
• Reduced medication adherence
• Possibly an increase in serious falls
• Possibly a J- or U- curve increase in CV risk
• Unnecessary use of limited health care
resources

30. Macchiavelli
The end justifies the means