update in hypertension guidelines: how low can you go? · intensity of bp lowering and choice of...

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.


Primary outcome in ACCORD-DM

<120 mmHg

<140 mmHg

Objectives


To:



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


To:



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


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


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

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


<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


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.


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


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


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


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


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


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


(>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


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


To:



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

update in hypertension guidelines: how low can you go? · intensity of bp lowering and choice of...

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