update in hypertension guidelines: how low can you go? · intensity of bp lowering and choice of...
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Update in Hypertension Guidelines:
How Low Can You Go?
Michael J. Choi, MD
MedStar Georgetown University Hospital
Washington DC, USA
Disclosures
• AstraZeneca Honorarium
• ABIM Nephrology Test Writing Committee.
Objectives
• Review 2017 ACC/AHA Hypertension Guideline in Regard
To:
o Techniques of BP measurement
o Intensive BP control in CKD
o Goal of <130/80 mmHg and potential risks in the elderly.
A 79 year old woman with long standing hypertension on HCTZ presents
to your office with a BP of 135/78 mmHg at the nurses station. She is
doing well. Would you add another anti-hypertensive medication?
A.Yes
B.No
4
ACC/AHA Definition of Hypertension
Whelton PK, et al. 2017 ACC/AHA Guidelines. Hypertension. 2018;71:e13-e115.
Multiple Conflicting BP Guidelines
Kramer HJ et al. Am J Kidney Dis. 2019;73:437-458.
Kramer HJ et al. Am J Kidney Dis. 2019;73:437-458.
Primary outcome in ACCORD-DM
<120 mmHg
<140 mmHg
Kramer HJ et al. Am J Kidney Dis. 2019;73:437-458.
Objectives
• Review 2017 ACC/AHA Hypertension Guideline in Regard
To:
o Techniques of BP measurement
o Intensive BP control in CKD
o Goal of <130/80 mmHg and potential risks in the elderly.
Measurement of BP
• BP often differs for many patients when measured in the clinic versus in non-clinic settings
• This guideline emphasizes the importance of best practice methods for BP measurement
Best Practice in Measuring BP
• In-office BP measurement may induce White Coat effect
• Automated Office Blood Pressure (AOBP) measurement
o Average of 3 measurements in quiet room
o Observer either present or not present
• AOBP:
o May be 5 – 20 mmHg lower than manual in-office SBP
o Probably correlates with awake ambulatory BP better than does manual
o SPRINT utilized AOBP measurement (Omron 907)
o Is < 120mmHg by SPRINT AOBP = < 130mmHg manual clinic BP
Myers MG et al. BMJ. 2011;34:d286.
Kjeldsen SE and Mancia G. Eur Heart J. 2016;2:79-80.
Filipovsky J et al. Blood Press. 2016;25:228-234.
Effect of Error
-Rest quietly for 5 minutes
-Inflate 20 mmHg past occlusion of
radial pulse
-Deflate 2 mmHg / sec
-Correct performance of all 11 steps- 1/159 (0.6%) of medical students
Rakotz MK et al. Clin J Hypertens. 2017;19:614-619
- 1/120 (0.8%) of Johns Hopkins med interns
Out of Office BP Measurements are Important
Home BP Monitoring (HBPM)- 2 readings AM and PM x 1
weekAdvantages
• Assessment in usual environment
• Better assessment of BP control and CV risko Niiranen T, et al. Hypertension. 2010;55:1346-1351, Agarwal R and Andersen MJ. Kidney Int. 2006;69:406-11
Siu AL et al. Ann Intern Med. 2015;163:778-786.
Ambulatory Blood Pressure Monitoring (ABPM)
Only 60 – 70% of Office BP Confirmed as Hypertension by ABPM/HBPM
Siu Albert L et al. Ann Intern Med. 2015;163:778-786.
ABPM Identifies Uncontrolled Nighttime BP
Pogue V. et al. Hypertension 2009;53:20-27.
617 African American Participants from AASK trial with Hypertensive CKD
ABPM Identifies Uncontrolled Nighttime BP
Pogue V. et al. Hypertension 2009;53:20-27.
617 African American Participants from AASK trial with Hypertensive CKD
15-30% of Gen Pop
45% AASK trial
ABPM is Better Predictor than In-Office BP
Siu Albert L et al. Ann Intern Med. 2015;163:778-786.
CV Events or mortality
Cardiac Events or mortality
Stroke
All cause mortality
0.5 1 2
HR (95% CI)
Techniques of BP Measurement
• Accurate assessment of BP is important
o Many of us do it incorrectly
• Consider utilizing AOBP
• Engage patients with HBPM
• Utilize ABPM to confirm adequacy of BP control
The BP Goal
• Why is it <130 mmHg?
SPRINT Randomized Controlled Trial
Target Systolic BP
Intensive Treatment
Goal SBP < 120 mm Hg
Standard Treatment
Goal SBP < 140 mm Hg
SPRINT design details available at: ClinicalTrials.gov (NCT01206062)
Ambrosius WT, et al. Clin Trials. 11:532-546, 2014.
1 Outcome: MI, ACS, CVA, CHF, CV death
Major Inclusion Criteria
• ≥ 50 years old, n=9361
• Systolic BP : 130 – 180 mm Hg (treated or untreated)
• Additional cardiovascular disease (CVD) risk:
➢ Clinical or subclinical CVD (excluding stroke)
➢CKD:• defined as eGFR 20 – 59 ml/min/1.73m2
➢ Framingham Risk Score for 10-year CVD risk ≥ 15%
➢ Age ≥ 75 years
Major Exclusion Criteria
• CVA
• DM
• eGFR <20 or proteinuria >1 g/d
Measured by AOBP
Cumulative Hazard for SPRINT Primary Outcome
CVD composite: first occurrence
MI, ACS, CVA, CHF, Death from CV cause
Cumulative Hazard for All-cause Mortality
NEJM 2015; 373: 2103-16
Agarwal R. J Am Heart Assoc 2017;6:e004536
Bland–Altman plot - mean differences between various blood pressure (BP)
recordings. SPRINT Trial
-12.7 mmHg in research AOBP vs. manual clinic
-12.0 mmHg in research AOBP vs. manual clinic
Systolic
Diastolic
N= 275
-46 to +20.7 mmHg
-33.2 to +17.4 mmHg
ACCORD Trial – BP control in patients with T2DM
ACCORD-BP - multicenter, 2 X 2 factorial RCT
Intensive BP
Goal SBP <120 mmHg
Standard BP
Goal SBP <140 mmHg
HgbA1c
<6%HgbA1c
7.0-7.9%
HgbA1c
<6%
HgbA1c
7.0-7.9%
Outcome of the Study
SBP <120 mmHg did not significantly reduce the composite of CVD death,
nonfatal MI, and nonfatal stroke compared with <140 mmHg
Forest Plot of HRs of Intensive vs. Standard SBP for CVD
Outcome in SPRINT and Two Glycemic Arms in ACCORD BP
Beddhu S et al. J Am Heart Assoc. 2018;7:e009326. DOI: 10.1161/JAHA.118.009326
Intensive BP
Std glycemia
SPRINT vs ACCORD comparison
• Intensive SBP lowering ’d hazard of the composite CVD end point
SPRINT HR: 0.75; (95% CI: 0.64 – 0.89)
ACCORD BP std glycemia arm HR: 0.77; (95% CI: 0.63 – 0.95)
• Patterns were similar for all-cause mortality.
Clinical implications of ACCORD re-analysis
These findings support the ACC/AHA guidelines of a
SBP goal of <130 mm Hg in patients with type 2 DM.
Objectives
• Review 2017 ACC/AHA Hypertension Guideline in Regard
To:
o Techniques of BP measurement
o Intensive BP control in CKD
o < 130 /80 mmHg and potential risks in the elderly.
BP Control in CKD
A SBP target <130 mmHg seems reasonable for individuals with
CKD stages 1-3b, with stronger evidence …persons with moderate
to severely increased urine albumin excretion. For individuals with
CKD stages 4 and 5 not receiving dialysis, there are insufficient
data.
Effects of Intensive BP Control in CKD
All Cause Mortality
Favors intensive control
Cheung AK et al. JASN. 2017;28:2812-2823.
Standard
Intensive
Effects of Intensive BP Control in CKD
CV Composite
Favors intensive controlStandard
Intensive
Cheung AK et al. JASN. 2017;28:2812-2823.
Intensive BP Lowering Reduces eGFR in CKD
-0.47 ml/min per 1.73m2/year
-0.32 ml/min per 1.73m2/year
Difference in slopes
after 6 months:
p = 0.03
Standard
Intensive
Cheung AK et al. JASN. 2017;28:2812-2823.
However AKI Increases CV and Mortality Risk in SPRINT
• ↑AKI in intensive BP group: 3.8% vs 2.3% (HR 1.64 (1.30-2.10), P<0.001)
risk of 1 outcome risk of all cause mortality Rocco MV et al. AJKD. Epub Nov 2017.; Ku E et al. JASN. 2017;28:2794-2801.; Ku E et al. JASN. Epub 2018. Dieter BP et al. Am J Nephrol. 2019;49:359-367.
CV Composite
HR 1.52 [1.05-2.2]
Death
HR 2.33 [1.56-3.48]
SPRINT and Kidneys- Summary
• ≥ 50 yo with HTN, eGFR 20 - 59 and <1g proteinuria
• SBP goal < 120 mmHg (by AOBP):
• lowers CV composite outcome and all-cause mortality
• no effect on slowing of CKD progression
• higher incidence of AKI
• Pts with AKI may have higher risk of CVD and death
BP Targets in the Elderly
Modified from Kramer HJ et al. Am J Kidney Dis 2019;73:437-458
1. KDIGO. Kidney Int Suppl 2012;2
2. ESH/ESC Task Force for the Management of Arterial Hypertension.J Hypertens 2013;31:1925-1938
3. James PA et al. JAMA 2014;311:507-520
4. Qaseem A et al. Ann Intern Med 2017;166:430437
5. Leung AA et al. Can J Cardiol 2016;32:569-588
6. Whelton PK at al. J Am Coll Cardiol 2018;71:e127-148
KDIGO1
(2012)
ESH/ESC2
(2013)
JNC83
(2014)
ACP/AAFP4
> 60 yo
(2017)
HTN Canada5
(2017)
ACC/AHA6
(2017)
Individualize <150/90 <150/90 SBP <150
SBP <140 if h/o CVA
OR high CV
risk
< 140/90
SBP <120 if >50 yo + high
CV risk
OR >75 yo
BUT <150 if > 80 yo
<130/80*
BP Targets in the Elderly
BP Targets in the Elderly
Modified from Kramer HJ et al. Am J Kidney Dis 2019;73:437-458
1. KDIGO. Kidney Int Suppl 2012;2
2. ESH/ESC Task Force for the Management of Arterial Hypertension.J Hypertens 2013;31:1925-1938
3. James PA et al. JAMA 2014;311:507-520
4. Qaseem A et al. Ann Intern Med 2017;166:430437
5. Leung AA et al. Can J Cardiol 2016;32:569-588
6. Whelton PK at al. J Am Coll Cardiol 2018;71:e127-148
KDIGO1
(2012)
ESH/ESC2
(2013)
JNC83
(2014)
ACP/AAFP4
> 60 yo
(2017)
HTN Canada5
(2017)
ACC/AHA6
(2017)
Individualize <150/90 <150/90 SBP <150
SBP <140 if h/o CVA
OR high CV
risk
< 140/90
SBP <120 if >50 yo + high
CV risk
OR >75 yo
BUT <150 if > 80 yo
<130/80*
BP Targets in the Elderly
Age-Related Issues
COR LOERecommendations for Treatment of Hypertension in
Older Persons
I A
Treatment of hypertension with a SBP treatment goal of less
than 130 mm Hg is recommended for noninstitutionalized
ambulatory community-dwelling adults (≥65 years of age) with
an average SBP of 130 mm Hg or higher.
IIa C-EO
For older adults (≥65 years of age) with hypertension and a
high burden of comorbidity and limited life expectancy, clinical
judgment, patient preference, and a team-based approach to
assess risk/benefit is reasonable for decisions regarding
intensity of BP lowering and choice of antihypertensive drugs.
Whelton PK at al. J Am Coll Cardiol 2018;71:e127-148
ASCVD risk equation predicts W >65 yo, M >70 yo with BP >130 mmHg is >10%
Compared Expected ASCVD Equation Risk vs Observed Risk
Rana JS et al. J Am Coll Cardiol 2016;67:2118-2130
N= 307,591 in Kaiser Permanente cohort ages 40-75
2636
participants
Standard
SBP <140 mm Hg
N=1317
Intensive
SBP <120 mm Hg
N=1319
• >75 yo, mean age 79.9 yo, follow up on 2510 participants
• Median f/u 3.14 yrs
• Primary CV outcome - nonfatal MI, ACS, stroke, acute decompensated heart failure, death from CV causes
• Secondary outcome - All-cause mortality
Williamson JD et al. JAMA. 2016;315(24):2673-2682
SPRINT SENIOR
Major
Exclusion
Criteria
Stroke
Diabetes
Congestive heart failure (symptoms or EF < 35%)
Dementia
Expected survival < 3 yrs
Weight loss > 10% in preceding 6 months
SBP < 110 mmHg following 1 minute standing
Nursing Home resident
Proteinuria >1 gram/day
eGFR < 20 ml/min/1.73m2 (MDRD)
Adherence concerns
Polycystic kidney disease
Major Exclusion Criteria
Outcome Intensive vs Standard
HR (95% CI)
P
value
CVD Primary Outcome(Nonfatal MI, CVA, ACS, acute decompensated heart
failure and CV death)
0.66 (0.51-0.85) .001
All-cause mortality 0.67 (0.49-0.91) .009
Primary outcome + All-cause mortality 0.68 (0.54-0.84) < 0.001
SPRINT SENIOROutcomes by BP Treatment Group
Williamson JD et al. JAMA. 2016;315(24):2673-2682
<140 -136
<120 -123
<140 -137
<140 -136
140-159 -146
<140 -135
140-149 -142
140-149 -150
Major Adverse Cardiovascular Events in the elderly: Outcomes of Intensive vs Standard BP Control Trials
Bavishi C et al J Am Coll Cardiol 2017;69:486-493
0.71(0.60, 0.84)
A 79 year old woman with long standing hypertension on HCTZ
presents to your office with a BP of 134/72 mmHg and is frail,
living in a nursing home.
Would you add another anti-hypertensive medication?
A.Yes
B.No
43
HYVET: BP treatment and Frailty
Warwick J et al. BMC Med. 2015;13:78
HYpertension in the Very Elderly TrialN=2656 >80 yo
Goal <150/90 vs. placeboAchieved 143 vs 158 mmHg
Excluded: recent CVA, CHF, dementia, CKD, nursing home resident
Williamson JD et al. JAMA. 2016;315(24):2673-2682
SPRINT SENIOR Trial –Outcome with Frailty
Age-Related Issues
COR LOERecommendations for Treatment of Hypertension in
Older Persons
I A
Treatment of hypertension with a SBP treatment goal of less
than 130 mm Hg is recommended for noninstitutionalized
ambulatory community-dwelling adults (≥65 years of age) with
an average SBP of 130 mm Hg or higher.
IIa C-EO
For older adults (≥65 years of age) with hypertension and a
high burden of comorbidity and limited life expectancy, clinical
judgment, patient preference, and a team-based approach to
assess risk/benefit is reasonable for decisions regarding
intensity of BP lowering and choice of antihypertensive drugs.
Whelton PK at al. J Am Coll Cardiol 2018;71:e127-148
The Predictive Values of Blood Pressure and Arterial
Stiffness in Institutionalized Very Aged Population
(PARTAGE Cohort)
Population Observational cohort study
N = 1127 > 80 yrs old who reside in nursing homes
Location France and Italy
Follow-up 2 years
Outcomes All-cause mortality by SBP level and number of
antihypertensive medications
Benetos A et al. JAMA Intern Med. 2015;175(6):989-995
Benetos A et al. JAMA Intern Med. 2015;175(6):989-995
Mortality and BP Target + number of anti-hypertensive meds
(PARTAGE Cohort)
< 130mmHg
HTN, Orthostatic Hypotension (OH) and
Falls in the elderly: MOBILIZE Cohort
BP Category OH at 1 min
(%)
No HTN<140/90 and no meds
2
Controlled HTN<140/90 + meds
5
Uncontrolled HTN>140/90 + meds
19*(p<.001)
Gangavati A et al J Am Geriatr Soc 2011:59;383-389
N=722 Prospective cohort of > 70 yo participants
HTN, Orthostatic Hypotension (OH) and
Falls in the elderly: MOBILIZE Cohort
Gangavati A et al J Am Geriatr Soc 2011:59;383-389
N=722, >70 yo prospective cohort, community dwelling
Time (days)
% o
f subje
cts
without
falls
HR 2.54 (1.27-5.09)
Uncontrolled HTN
Time (days)
Controlled HTN (< 140/90 mmHg)
Falls in ACCORD Trial: n=3099 T2DM Intensive BP (<120) achieved 119 mmHgStandard BP (<140) achieved 133 mmHg
Margolis KL et al J Gen Intern Med2014;29:1599-1606
62.2 + 6.4 yo62.7 + 6.7 yo
Fractures in ACCORD Trial: n=3099 T2DM Intensive BP (<120) achieved 119 mmHgStandard BP (<140) achieved 133 mmHg
Margolis KL et al J Gen Intern Med2014;29:1599-1606
62.2 + 6.4 yo62.7 + 6.7 yo
Hazard Ratio 0.79, 95% (CI 0.62-1.01), p=0.06
Fir
st n
on
-sp
ine f
ract
ure
s (%
)
Years post randomization
Outcome Intensive vs Standard
HR (95% CI)
P value
Serious Adverse Events 0.99 (0.89-1.11) NS
Hypotension 1.71 (0.97-3.09) NS
Injurious Falls 0.91 (0.65-1.29) NS
Syncope 1.23 (0.76-2.00) NS
Orthostatic Hypotension 0.90 (0.76-1.07) NS
Electrolyte abnormalities 1.51 (0.99-2.33) NS
SPRINT SENIOR TrialOutcomes by BP Treatment Group
Outcome Intensive vs Standard
HR (95% CI)
P
value
Acute Kidney Injury 1.41 (0.98-2.04) NS
CKD participants (44%)
> 50% ↓eGFR, dialysis, transplant 1.68 (0.49-6.49) 0.42
Incident albuminuria 0.96 (0.53-1.75) 0.90
Non CKD participants (56%)
> 30% ↓eGFR to <60
ml/min/1.73m2, ,
dialysis, transplant*
3.14 (1.66-6.37)(Events 37/726 vs 13/732)
<0.01
Incident albuminuria 0.80 (0.46-1.35) .40
SPRINT SENIORKidney Outcomes by BP Treatment Group
Outcome Intensive vs Standard
HR (95% CI)
P
value
Acute Kidney Injury 1.41 (0.98-2.04) NS
CKD participants (44%)
> 50% ↓eGFR, dialysis, transplant 1.68 (0.49-6.49) 0.42
Incident albuminuria 0.96 (0.53-1.75) 0.90
Non CKD participants (56%)
> 30% ↓eGFR to <60
ml/min/1.73m2, dialysis, transplant* 3.14 (1.66-6.37)(Events 37/726 vs 13/732)
<0.01
Incident albuminuria 0.80 (0.46-1.35) 0.40
SPRINT SENIORKidney Outcomes by BP Treatment Group
<140 -136
<120 -123
<140 -136
140-159 - 146
<140 - 135
140-149 - 150
Bavishi C et al J Am Coll Cardiol 2017;69:486-493
Elderly: Kidney Risks of Intensive vs Standard BP Control Trials
Fixed Effects
Kidney Failure
Age-Related Issues
Whelton PK at al. J Am Coll Cardiol 2018;71:e127-148
(>150/90 mmHg)
1. “…caution is advised in initiating antihypertensive pharmacotherapy with
2 drugs in older patients because hypotension or orthostatic hypotension
may develop…”
2. “The stepped-care approach is also reasonable in older adults…”
SPRINT-MIND
HR 0.83 (0.67-1.04), p =.10
Outcome Intensive vs Standard
HR (95% CI)
P
value
Mild Cognitive Impairment 0.81 (0.69 – 0.95) .007
Mild Cognitive Impairment or Probable Dementia 0.85 (0.74-0.97) .01
Mean age 67.9 years
SPRINT MIND Investigators JAMA 2019;321:553-561
Conclusion
s
BP goal < 130/90 mmHg is reasonable in the elderly
who are community-dwelling and have limited co-
morbidities
• Watch carefully for kidney outcomes with and without CKD
For those with high co-morbidity and limited life
expectancy – individualize BP goals
Stepped-care instead of 2 drugs at once
Cohorts vs trials may have differing results on BP
treatment intensity
Hypertension Highlights
o Techniques of BP measurement• Accurate BP measurement
• Consider Out of office measurements
o Intensive BP control in CKD• CV and mortality benefit
• Increased risk for AKI that may eliminate CV and mortality benefit
o In the elderly• BP goal < 130/90 mmHg is reasonable in the elderly who are community-
dwelling and have limited co-morbidities
• Watch the kidneys
James PA et al. JAMA 2014
James et al. JAMA published online December 18, 2013
JNC 8
CKD
BP <140/90 mmHg
ACEI/ARB alone or in combination with other drug class
Objectives
• Review 2017 ACC/AHA Hypertension Guideline in Regard
To:
o Techniques of BP measurement
o Intensive BP control in CKD
oManagement of resistant hypertension
Resistant Hypertension
• 130/80 on 3 meds with diuretic
• Exclude Pseudoresistance
• Address Lifestyle Factors
• Evaluate Secondary Causes
• Pharmacologic Treatment
• Refer to Specialist
• Only 10% to 15% of patients with
apparent treatment-resistant
hypertension have true resistance to
medications
• ~40% of CKD patients have apparent
treatment-resistant hypertension
Thomas G et al. Hypertension. 2016;67:387-396.; Carey RM et al. Hypertension. 2018;72:e53-e90.
Optimal 3 Drug Regimen
• ACEi or ARB
• Long acting dihydropyridine CCB
• Thiazide-like diuretic
Change the Diuretic
• HCTZ – more than 90% of thiazide prescriptions in patients with treatment resistance
Hwang AY et al. Hypertension. 2016;68:1349-1354.
Change the Diuretic
Roush GC et al. Hypertension. 2015;65:1041-1046.
Meta-analysis of HCTZ versus chlorthalidone or indapamide
14 trials, 883 patients
∆SPB = -3.6 mmHg
∆SPB = -5.1 mmHg
Chlorthalidone HCTZ more potent
more potent
INDAP more potent HCTZ more potent
• PATHWAY-2 Trial
• Uncontrolled clinic and
home BP on ACEi/ARB,
CCB, and diuretic
• Spironolactone should
be add-on therapy of
choiceo Aldosterone breakthrough
o HyperK may limit use in CKD
Williams B, et al. Lancet. 2015;386:2059-68.
Add a 4th Drug
Add a 4th Drug
-7
-4
-12
-6
-14
-12
-10
-8
-6
-4
-2
024-hour SBP 24-hour DBP
Clonidine
Spiro46
44
0
10
20
30
40
50
60
70
80
90
100
Percent <130/80 @ 12 weeks
Krieger EM et al. Hypertension. 2018;71:681-690.
• ReHOT Trial
• 187 Stage 2 HTN on
ACEi/ARB, CCB, and
diuretic
• Clonidine vs Spiro
• Similar rate of control,
although greater BP
reduction with spiro
Add a 4th Drug
-7
-4
-12
-6
-14
-12
-10
-8
-6
-4
-2
024-hour SBP 24-hour DBP
Clonidine
Spiro46
44
0
10
20
30
40
50
60
70
80
90
100
Percent <130/80 @ 12 weeks
Krieger EM et al. Hypertension. 2018;71:681-690.
• ReHOT Trial
• 187 Stage 2 HTN on
ACEi/ARB, CCB, and
diuretic
• Clonidine vs Spiro
• Similar rate of <
130/80 mmHg,
although greater BP
reduction with spiro
Resistant Hypertension– Summary
• Apparent treatment resistant hypertension is common in CKD
• Utilize a thoughtful approach to management
• Appropriate 4 drug regimen
o ACE inhibitor (or ARB)
o Long-acting dihydropyridine CCB
o Diuretic (usually a thiazide-like)
o Spironolactone/Eplerenone