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BB
ACEI
ARB
CCB
AA Diuretic
ACC/AHA Clinical Practice Guidelines
Hierarchical Grading System
ACC/AHA Clinical Practice Guidelines
Hierarchical Grading System
Class I
(Useful &
Effective)
(Benefit >>>
risk)
(Highly
recommended)
Class II
(Conflicting Evidence)
Class III
(Not useful/
effective, may
be harmful)
(No benefit/Harm)
(Not
recommended)
IIa
(Benefit >>risk)
(Reasonably
recommended)
IIb
(Benefit ?
risk)
(May be
considered)
Level A
(Multiple
randomized
clinical trials)
Level B
(Single
randomized trial
or
nonrandomized
studies
Level C
(Consensus
opinion, case
studies, or
standard of care)
Scientific Evidence Underlying the
ACC/AHA Clinical Practice Guidelines
Among ACC/AHA guidelines updated by Sept. 2008:
48% increase (1330 to 1973) in # of recommendations
occurred, the largest # being Class II (conflicting
evidence)
Of 16 current guidelines with level of evidence recs:
12% (314/2711) are Level A (multiple RCTs)
46% (1246/2711) are Level C (expert opinion, no
RCTs)
Only 9% (245/2711) are Class I and Level A
Increased Resources($) are needed to fund trials
supporting guideline development
Tricoci, et al. JAMA. 2009; 301: 831 - 841
Update clinical recommendations on BP, cholesterol, and obesity
Use systematic evidence review process
Use evidence & recommendations grading
Standardize & coordinate approaches
Develop consistent recommendations for lifestyle & risk
assessment
Create integrated CV risk reduction recommendations
Individual risk factor guidelines + lifestyle and risk assessment
+ additional CVD risk reduction approaches
Develop comprehensive approach to implementation
Write guidelines clearly so they are implementable
Address patient, clinician, and systems levels
Develop and disseminate materials & tools
Develop an evidence-based implementation plan
Establish a National Program to Reduce Cardiovascular Risk
NHLBI Cardiovascular Prevention Guidelines
New Directions
NHLBI Systematic Review and
Guideline Development Process
Literature Searched;
Eligible Studies
Identified
Studies Quality Rated;
Data Abstracted
Evidence Tables
Developed;
Body of Evidence
Summarized
External Review
of Recommendation
Drafts; Revised
as Needed
Guidelines
Disseminated &
Implemented
Graded Evidence
Statements &
Recommendations
Developed
Expert Panel
Selected
Topic Area
Identified
Critical Questions
&Study Eligibility
Criteria Identified
NHLBI Evidence Quality Rating and
Recommendation Strength
Evidence Quality
High
Well-designed and
conducted RCTs
Moderate
RCTs with minor limitations
Well-conducted
observational studies
Low
RCTs with major limitations
Observational studies with
major limitations
Recommendation Strength
A Strong
B Moderate
C Weak
D Against
E Expert Opinion
N No Recommendation
JNC 2013:
Initial Question Areas Being Addressed
Among adults, does treatment with antihypertensive
pharmacological therapy to a specific BP goal lead to
improvements in health outcomes? (how low should
you go)
Among adults with hypertension, does initiating
antihypertensive pharmacological therapy at specific BP
thresholds improve health outcomes? (when to initiate
drug treatment)
In adults with hypertension, do various antihypertensive
drugs or drug classes differ in comparative benefits and
harms on specific health outcomes? (How do we get
there?)
Inclusion/Exclusion Criteria for Studies
Randomized Controlled trials
1966-present
Minimum one year follow-up
Studies with samples size <100
excluded
JNC 2013:
Initial Question Areas Being Addressed
(how low should you go) N=56
(when to initiate drug treatment) N=26
(How do we get there?) N=66
BP Level-How Low to go
General population
Elderly
Kidney Disease
2013 BP Guideline Goal
<140/90 mmHg
KDIGO/KDOQI
NICE
Latin Am. Consortium for Diabetes Management
Am Diabetes Assoc.- <140/80 mmHg
ONTARGET: Relationships Between
Outcome Risks and In-Trial BP
J-shaped curve (nadir 130 mm Hg) for primary outcome
a
, MI, CV mortality (not stroke)
Continual risk increase (no J-shaped curve) for stroke
Suggests increased risk of events in patients with extensive vascular disease when BP is
decreased below a critical level
A
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Sleight P, et al. J Hypertens. 2009;27:1360-1369.
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Primary study outcome
a
Composite of cardiovascular death, MI, stroke, or
hospitalization for congestive heart failure (CHF).
112 121 126 130 133 136 140 144 149 161
0
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0
0.5
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Weber M et.al. submitted Am J Med.
CV outcomes from the ACCOMPLISH trial
16.3
8.6
9.6
5.1
9.9
5.3
0
5
10
15
20
Primary Endpoint
Death/MI/
stroke/revascularization
All-cause
mortality
O
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c
o
m
e
(
%
)
SBP > 140 mmHg
SBP 130140 mmHg
SBP < 130 mmHg
OUTCOMES: (MI, stroke, revascularization, all-cause mortality)
ACCF/AHA 2011 Expert Consensus
Document on Hypertension in the
Elderly
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Aronow W et.al. JACC 2011;57:2037-2114
Percentage of People in Outcome Trials of the
Elderly Taking > 2 Antihypertensive Medication
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ACC Guidelines in Elderly 2011- JACC 2011
Major Take Home Message of Elderly
Guidelines-Management
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Aronow W et.al. JACC 2011;57:2037-2114
BP level and CKD
M 2!J45H4 778'
24
Composite Ranking for Relative Risks by glomerular
filtration rate (GFR) and Albuminuria (Kidney Disease:
Improving Global Outcomes (KDIGO) 2009
25
Levey AS et.al. Kidney Int 2010; doi: 10.1038/ki.2010.483
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Steno-2: Intensive Multiple Risk Factor
Management
Cardiovascular Events
Years of Follow-up
No. at Risk
Intensive therapy 80 72 65 61 56 50 47 31
Conventional therapy 80 70 60 46 38 29 25 14
Intensive
Therapy
Conventional
Therapy
0 1 2 3 4 5 6 7 8 9 10 11 12 13
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HR=0.41; p< 0.001
Absolute RR= 29%
HR for Total
Mortality: 0.54;
p=0.02
Absolute RR= 20%
Gaede P, et al. NEJM. 2008;358:580-591.
Changes in Selected Risk Factors during the
Interventional Study and Follow-up Period (13.3 years).
Gde P et al. N Engl J Med 2008;358:580-591.
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* Indicates use with diuretic
Group
Goal BP
(mmHg)
Initial Therapy
ABA (2u12) <1Su8u ACE InhibitoiARB*
KB0QI (NKF) (2uu7) <1Su8u ACE InhibitoiARB
ESB (2uu7+ 2uu9) <1Su8u ACE InhibitoiARB*
KB0QI (NKF) (2uu4) <1Su8u ACE InhibitoiARB*
}NC 7 (2uuS) <1Su8u ACE InhibitoiARB*
Am. Biabetes Assoc (2uuS) <1Su8u ACE InhibitoiARB*
Canauian BTN Soc. (2uu2) <1Su8u ACE InhibitoiARB*
Am. Biabetes Assoc (2uu2) <1Su8u ACE InhibitoiARB*
Natl. Kiuney Founuation (2uuu) <1Su8u ACE Inhibitoi*
Biitish BTN Soc. (1999) <14u8u ACE Inhibitoi
WB0ISB (1999) <1Su8S ACE Inhibitoi
}NC vI (1997) <1Su8S ACE Inhibitoi
30
SBP=systolic blood pressure. *Target blood pressure control groups in ACCORD defined as
<120 mm Hg (intensive) and <140 mm Hg (standard).
Copley JB, Rosario R. Dis Mon. 2005;51:548-614.
The ACCORD Study Group. N Engl J Med. 2010 Mar 14. [Epub ahead of print]
ALLHAT 138
HOT 138
ACCOMPLISH 132
ACCORD (intensive)* 119
ACCORD (standard)* 133
INVEST 133
IDNT 138
RENAAL 141
ABCD 132
UKPDS 144
MDRD 132
AASK 128
Multiple Medications Are Required to
Achieve BP Control in Clinical Trials
Hypertension
Diabetes
Kidney
disease
No. of BP medications
1 2 3 4
SBP achieved
(mm Hg) Trial
Blood Pressure Targets in Chronic Kidney
Disease: Proteinuria as an Effect Modifier
3 RCTs (8 reports) with a total of 2272 participants
MDRD (Modification of Diet in Renal Disease)
Study
AASK (African American Study of Kidney Disease
and Hypertension) Trial
REIN-2 (Ramipril Efficacy in Nephropathy 2) trial
2- to 4-year trial follow-up
Upadhyay A, et al. Annals Intern Med 3/2011
Peralta, C. A. et al. Arch Intern Med 2012;172:41-47.
Rates of end-stage renal disease per 1000 person-years
16,000+ persons
Mean follow-up 2.8 yrs
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Initial Combinations of Medications*
Thiazide-Like Diuretics
ACE inhibitors
or
ARBs
Calcium
antagonists
* Compelling indications may modify this.
-blockers should be included in the regimen if
there is a compelling indication for a -blocker
Conclusion (my opinion)
The BP for everyone will be <140/90 mmHg
BP for those >60- <150/90 mmHg
Combinations of RAS blockers with thiazide
diuretics or RAS blockers and
dihydropyridine CCBs are acceptable first
line combos to get BP to goal, if >20/10
mmHg above goal