Shawna Nesbitt, MD...N Engl J Med. Nov 26; 2015 373(22):2103‐2116 SPRINT TRIAL: Systolic Blood Pressure Trend The SPRINT Research Group. N Engl J Med. 2015;373:2103‐2116 SPRINT

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Saturday General Session

HypertensionUpdate:NavigatingtheNewGuidelinesandMedications

ShawnaNesbitt,MDProfessor of Medicine and Associate Dean of Student Affairs Office of Student Diversity and Inclusion UT Southwestern Medical Center Dallas, Texas EducationalObjectivesBy completing this educational activity, the participant should be better able to:

1. Discuss the significance of early detection and effective treatment of hypertension.

2. Address barriers to care among patients with hypertension and assess treatment barriers in the elderly.

3. Discuss the recommendations of the JNC8. 4. Construct a management plan for patients with hypertension and discuss

methods for treating for resistant hypertension.

SpeakerDisclosure Dr. Nesbitt has disclosed that she has received grant support from Quantum Genomics, she is a consultant for Relypsa, and she is on the advisory board for Quantum Genomics and Reylpsa.

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Shawna D. Nesbitt, MD, MS

Professor of Medicine

Associate Dean

UT Southwestern Medical School

“Hypertension Update: Navigating the New Guidelines”

SPEAKER DISCLOSURE

• Dr. Nesbitt has disclosed that she has received grant support from Quantum Genomics, she is a consultant for Relypsa, and she is on the advisory board for Quantum Genomics and Reylpsa.

EDUCATIONAL OBJECTIVES

By completing this educational activity, the participant should be better able to:1. Discuss the significance of early detection and effective

treatment of hypertension.2. Address barriers to care among patients with hypertension and

assess treatment barriers in the elderly.3. Discuss the recommendations of the JNC8.4. Construct a management plan for patients with hypertension

and discuss methods for treating for resistant hypertension.

BASELINE BP PREDICTS PROGRESSION TO HYPERTENSION

4‐year Hypertension Incidence rates

Optimal = <120/80 mm Hg Normal = 120‐130/80‐85 mm Hg High Normal = 130‐139/85‐89 mm Hg

Adjusted for sex, age, BMI, and baseline BP

Vasan RS. Lancet. 2001;358:1682

KAPLAN‐MEIER CURVES OF CLINICAL HYPERTENSION IN THE TWO GROUPS

0 1 2 3 4

Years in study

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

% Cumulative in

cidence

Candesartan

Placebo

Candesartan 391 356 309 191 128

Placebo 381 269 184 118 85

Numbers under the graph refer to hypertension‐free individuals

2 YearsRR ↓66%AR ↓ 26%

4 YearsRR ↓15.8AR ↓ 9.6

Julius S, Nesbitt SD, et al. NEJM. 2006;354Lancet, 2002; 360:1903‐1913

CORONARY ARTERY DISEASE MORTALITY STROKE MORTALITY

Risk of CAD and Stroke Mortality by SBP

Lewington S, et.al. Lancet. 2002;360:1903‐1913

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3 4

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MORTALITY FROM HIGH BLOOD PRESSURE HIGHER IN AFRICAN AMERICANS

Age‐adjusted Mortality Rates Attributable to Hypertension, 2014

Mortality Rate per 100,000

African American

Women Men Women

20

10

30

40

5050.1

19.3

35.6

15.8

0

60

Men

White

Adapted from Benjamin EJ, et al. Circulation. 2017.

ADULT BLOOD PRESSURE CATEGORIESBP Category SBP DBP

Normal <120 mm Hg and <80 mm Hg

Elevated 120–129 mm Hg

and <80 mm Hg

Hypertension

Stage 1 130–139 mm Hg

or 80–89 mm Hg

Stage 2 ≥140 mm Hg or ≥90 mm Hg

• *Individuals with SBP and DBP in 2 categories should be designated to the higher BP category.• BP indicates blood pressure (based on an average of ≥2 careful readings obtained on ≥2

occasions, as detailed in DBP, diastolic blood pressure; and SBP systolic blood pressure.

Whelton PK, et.al. ACC/AHA/AAPA/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA. Guideline for the prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension. 2017; Nov 13

PREVALENCE OF HYPERTENSION BASED ON 2 SBP/DBP THRESHOLDS*†

SBP/DBP ≥130/80 mm Hg or Self-Reported

Antihypertensive Medication†

SBP/DBP ≥140/90 mm Hg or Self-Reported Antihypertensive

Medication‡Overall, crude 46% 32%

Men(n=4717)

Women(n=4906)

Men(n=4717)

Women(n=4906)

Overall, age-sex adjusted

48% 43% 31% 32%

Age group, y20–44 30% 19% 11% 10%45–54 50% 44% 33% 27%55–64 70% 63% 53% 52%65–74 77% 75% 64% 63%75+ 79% 85% 71% 78%

Race-ethnicity§Non-Hispanic White 47% 41% 31% 30%Non-Hispanic Black 59% 56% 42% 46%Non-Hispanic Asian 45% 36% 29% 27%

Hispanic 44% 42% 27% 32%

• The prevalence estimates have been rounded to the nearest full percentage.• *130/80 and 140/90 mm Hg in 9623 participants (≥20 years of age) in NHANES 2011–2014.• †BP cut points for defini on of hypertension in the present guideline. • ‡BP cut points for defini on of hypertension in JNC 7.• §Adjusted to the 2010 age‐sex distribution of the U.S. adult population.• BP indicates blood pressure; DBP, diastolic blood pressure; NHANES, National Health and Nutrition Examination Survey; and SBP, systolic blood pressure.Whelton PK, et al. Guideline for the prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension. 2017; Nov 13

Muntner, P et al. “Potential US Population Impact of the 2017 ACC/AHA High Blood Pressure Guideline.” Circulation. 2017.

42%46%

31% 30%

59%56%

47%

41%

0%

10%

20%

30%

40%

50%

60%

70%

Black men Black women White men White women

Prevalence of Hypertension Based on BP Thresholds (NHANES)

JNC 7‐‐140/90 mmHg 2017 ACC/AHA‐‐130/80 mmHg

LANGUAGE AS A BARRIER TO HEALTHCARE

“Triple Threat”1. Language differences2. Cultural differences

associated with language3. Low health literacy

Schyve PM. J Gen Intern Med. 2007;22(suppl2);360

5 AREAS OF SOCIAL DETERMINANTS OF HEALTH (SDOH)

Education• High School Graduation• Enrollment in Higher Education• Language and Literacy• Early Childhood Education and Development

Neighborhood and Built Environment• Access to foods that support healthy Eating Patterns• Quality of Housing• Crime and Violence• Environmental Conditions

Social and Community Context• Social Cohesion• Civic Participation• Discrimination• Incarceration

Health and Health Care• Access to Health Care• Access to Primary Care• Health Literacy• Provider Bias• Cultural Competency

Economic Stability• Poverty• Employment• Food Insecurity• Housing Instability

Social Determinants Of Health

Healthy People 2020; Healthy People.Gov

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RECOMMENDATION FOR ACCURATE MEASUREMENT OF BP IN THE OFFICE

COR LOERecommendation for Accurate Measurement

of BP in the Office

I C‐EO

For diagnosis and management of high BP, proper methods are recommended for accurate measurement and documentation of BP.

What’s wrong with this picture?

Abbasi J. Medical Students Fall Short on Blood Pressure Check Challenge. JAMA 2017

OUT‐OF‐OFFICE AND SELF‐MONITORING OF BP

COR LOERecommendation for Out‐of‐Office and Self‐

Monitoring of BP

I ASR

Out‐of‐office BP measurements are recommended to confirm the diagnosis of hypertension and for titration of BP‐lowering medication

Home BP monitoring

24 hr. ambulatory BP monitoring

Siu et al. Ann Intern Med. 2015;163:1‐10

“The USPSTF recommends obtaining measurements outside of the clinical setting (Ambulatory or Home BP) for diagnostic confirmation before starting treatment. (Grade A)”

BPmm Hg

0

50

100

150

200

250

16:00 24:00 16:00

Sleep

hr:min

Normal

15:00 24:00

Officevisits

White Coat Effect

White Coat HypertensionWhite Coat Hypertension24 Hour Ambulatory BP Monitoring

24 Hour Ambulatory BP Monitoring24 Hour Ambulatory BP Monitoring

0

60

100

140

180

BloodPressuremm Hg

4 pm midnight 4 pm

AsleepAwake

Dow Jones Down

13 14

15 16

17 18

4

Masked HTN and White Coat HTN in Dallas Heart Study

Population‐based probability

sample (n =3,027

50% African Americans

49% female)

Median follow up 9.5 yearsWCH 3%

Masked HTN 18%

Sustained HTN 12%

Tientcheu, et al. J Am Coll Cardiol. 201517;66(20):2159‐69.

Increased CV Complications in WCH and MH

Sustained HTN

Masked HTN

White coat HTN

Normotensives

Tientcheu, et al. J Am Coll Cardiol. 2015 17;66(20):2159‐69

HOW ACCURATE ARE HOME BP MONITORS ?A CROSS‐SECTIONAL STUDY IN 210 PATIENTS

Ruzicka, et al. PLOS ONE. June 2016

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21 22

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• Patients at increased cardiovascular risk but without diabetes were assigned to intensive treatment of systolic BP (target, <120 mm hg) or standard treatment (target, <140 mm hg).

• After a median of 3.26 years, the rate of cardiovascular events was significantly lower with intensive treatment.

SPRINT TRIAL: Systolic Blood Pressure Intervention Trial

A Randomized Trial of Intensive versus Standard Blood-Pressure Control

JT Wright, et al. A Randomized Trial of Intensive versus Standard Blood‐Pressure Control. N Engl J Med. Nov 26; 2015 373(22):2103‐2116

SPRINT TRIAL: Systolic Blood Pressure Trend

The SPRINT Research Group. N Engl J Med. 2015;373:2103‐2116

SPRINT Trial: Primary Outcome and Death from Any Cause


SPRINT Study Primary Outcome According to Subgroups


SPRINT TRIAL: Primary and Secondary Outcomes and Renal Outcomes.


SPRINT TRIAL: Primary and Secondary Outcomes and Renal Outcomes.


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SPRINT TRIAL CONCLUSION

Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm hg, as compared with less than 140 mm hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive‐treatment group.

The SPRINT Research Group. N Engl J Med. 2015;373:2103‐2116PERKOVIC V, RODGERS A. N ENGL J MED. 2015;373:2175‐2178.

Outcomes Data from SPRINT and the ACCORD Trial and Combined Data from Both Trials

RECOMMENDATIONS FOR TREATMENT AND FOLLOW‐UP OF ELEVATED BP

Whelton PK, et.al. Guideline for the prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension 2017; Nov 13

Color coded by the class of of recommendation using the ACC/AHA equations.

Sex: Male

Age

Race

Diabetes

Systolic BP

Treatment of HTN

Total Cholesterol

HDL‐Cholesterol

Smoking

ASCVD Risk: Pooled Cohort Equation

BP Thresholds for and Goals of Pharmacological Therapy in Patients with Hypertension According to Clinical Conditions

Clinical Condition(s)

BP

Threshold,

mm Hg

BP Goal,

mm Hg

GeneralClinical CVD or 10‐year ASCVD risk ≥10% ≥130/80 <130/80No clinical CVD and 10‐year ASCVD risk <10% ≥140/90 <130/80Older persons (≥65 years of age; noninstitutionalized,

ambulatory, community‐living adults)

≥130 (SBP) <130 (SBP)

Specific comorbiditiesDiabetes mellitus ≥130/80 <130/80Chronic kidney disease ≥130/80 <130/80Chronic kidney disease after renal transplantation ≥130/80 <130/80Heart failure ≥130/80 <130/80Stable ischemic heart disease ≥130/80 <130/80Secondary stroke prevention ≥140/90 <130/80Secondary stroke prevention (lacunar) ≥130/80 <130/80Peripheral arterial disease ≥130/80 <130/80


CHOICE OF INITIAL MEDICATION

COR LOE Recommendation for Choice of Initial Medication

I ASR

For initiation of antihypertensive drug therapy, first‐line agents include thiazide diuretics, CCBs, and ACE inhibitors or ARBs.

SR indicates systematic review.

Beta Blockers are NOT first line Drug therapy


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CHOICE OF INITIAL MONOTHERAPY VERSUS INITIAL COMBINATION DRUG THERAPY

COR LOERecommendations for Choice of Initial Monotherapy

Versus Initial Combination Drug Therapy*

I C‐EO

Initiation of antihypertensive drug therapy with 2 first‐line agents of different classes, either as separate agents or in a fixed‐dose combination, is recommended in adults with stage 2 hypertension and an average BP more than 20/10 mm Hg above their BP target.

IIa C‐EO

Initiation of antihypertensive drug therapy with a single antihypertensive drug is reasonable in adults with stage 1 hypertension and BP goal <130/80 mm Hg with dosage titration and sequential addition of other agents to achieve the BP target.

Whelton PK, et.al. Guideline for the prevention, Detection, Evaluation, and Management of High BP in Adults. Hypertension 2017; Nov 13

PART 1 SUMMARY

• BP threshold and goal generally lower to 130/80 mmHg (though not SPRINT level)

• However, drug Rx not recommended for low risk patients with BP 130‐139/80‐89 mmHg

• ASCVD risk assessment is recommended in conjunction with BP to guide HTN Rx

• Beta blocker is not first line Rx for HTN without other indication• For patients with stage II HTN BP >= 140/90 mmHg 2 drug

combination preferred (2‐in1 combo pill, if possible)

BP Measurement in SPRINT: Does automated Office BP measurement matter ?

• Automated BP monitors (OMRON) by research nurses

• Monitor is programmed to have delay start after 5 min rest

• 3 measurements separated by 1 min with all 3 average

• Research personnel encourage to leave the room but not a must

Always Alone (4,082 participants at 38 sites): Alone for both 5 min rest and 3 BP readings

Never Alone (2,247 participants at 25 sites): Personnel in the room the entire time

Alone for Rest (1746 participants at 19 sites): Alone for 5 min rest but not during 3 BP readings

Alone for BP Measurement (570 participants at 6 sites): Alone only during 3 BP readings but not during rest

CV Outcome by Method of BP Measurement in SPRINT

Johnson et al. Abstract AHA LBCT Meeting. 2017.

Stroke CHD Total

–6 –4 –3

–8 –5 –4

–14 –9 –7

Reduction in BP

Population‐Based Strategy

SBP Distributions

BeforeIntervention

AfterIntervention

% Reduction in MortalityReduction in SBP mmHg

2

3

5

SBP<140SBP<135

CASE 1

• A 78 yo woman with HTN presents for follow up. She lives alone, but is quite active.

• Taking amlodipine 10mg daily and chlorthalidone 25mg daily for several years. Brings home blood pressure logs for past 3 days showing values ranging 138/68‐149/75 mm Hg. She is concerned about lowering her BP too much as she is worried about falling.

• BP is 146/68 R arm, Height 5’1’’, Weight 109lbs, BMI‐ 20.6 kg/m2

• Exam otherwise unremarkable• ECG – normal sinus rhythm, no LVH• Labs – Cr‐0.7mg/dL

• What do you recommend?

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39 40

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SPRINT STUDY: AGE ≥75Overall Age≥75

HR NNT* HR NNT*

PrimaryOutcome

0.75 (0.64–0.89)

610.66

(0.51‐0.85)27

CV Death0.57

(0.38–0.85)172

0.60(0.33‐1.09)

116

All Cause Mortality

0.73(0.60–0.90)

900.67

(0.49‐0.91)41

* ~3.2 years f/u1°outcome= myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes

SPRINT Investigators NEJM 2015;373:2103‐2116

Williamson J et al. 2016 JAMA;315:2673‐2682.

SPRINT SENIOR Sub StudyBenefit of Intensive BP Reduction in Frail Elderly

Williamson. JAMA. 2016;315(24):2673‐2682

Cardiovascular Outcome in SPRINT Participants with CKD at Baseline

HR (95% CI)0.81 (0.63‐1.05)

Cheung, et al. JASN, June 2017

Intensive

Standard HR (95% CI)0.90 (0.44‐1.83)

Cheung, et al. JASN, June 2017

RENAL OUTCOME IN SPRINT PARTICIPANTS WITH CKD AT BASELINE (EGFR < 60 ML/MIN/1.73 M2)

Outcome: decrease. in eGFR > 50% or ESRD

All Cause Mortality in SPRINT Participants with CKD at Baseline

Standard

Intensive

Cheung et al. J Am Soc Nephrol. Jun 22 2017

Intensive

Standard

SPRINT: Patient Reported Outcomes

Berlowitz. NEJM. 2017;377:8

Physical HealthDepression Scale

Mental Health

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45 46

47 48

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Effect of Intensive vs. Standard Blood Pressure Control on Probable Dementia

SPRINT. Mind. JAMA 2019;32:553‐561

Shaded regions indicate 95% CI. Median follow‐up time 5.14 years vs. 5.07 years. Hazard Ratio 0.83 95% CI 0.67‐1.04 P=0.1

Effect of Intensive vs. Standard Blood Pressure Control on Probable Dementia

SPRINT. Mind. JAMA2019;32:553‐561

OUTCOMES OF INTENSIVE BLOOD PRESSURE LOWERING IN OLDER HYPERTENSIVE PATIENTS

Bavishi C. JACC. 2017;69:486‐493

CASE 2

• 66 yo African‐American man is being seen for a recent gout flare.

He has T2DM and hyperlipidemia.

• He takes HCTZ 25mg and amlodipine 10mg.

• His blood pressure in the office is 138/94 mm Hg which is similar

to home readings.

• Labs show eGFR of 40 with a positive urine dipstick for protein.

• What’s his goal and what are his options?

Muntner, P et al. “Potential US Population Impact of the 2017 ACC/AHA High Blood Pressure Guideline.” Circulation 2017.

42%46%

31% 30%

59%56%

47%

41%

0%

10%

20%

30%

40%

50%

60%

70%

Black men Black women White men White women

Prevalence of Hypertension Based on BP Thresholds (NHANES)

JNC 7‐‐140/90 mmHg 2017 ACC/AHA‐‐130/80 mmHg

• DM or CKD patients are automatically placed in the high‐risk category. For initiation of RAS inhibitor or diuretic therapy, assess blood tests for electrolytes and renal function 2 to 4 weeks after initiating therapy.

• †Consider ini a on of pharmacological therapy for stage 2 hypertension with 2 antihypertensive agents of different classes.

• Patients with stage 2 hypertension and BP ≥160/100 mm Hg should be promptly treated, carefully monitored, and have medication dose adjustment as necessary to control BP.

• Reassessment includes • BP measurement• Detection of orthostatic hypotension in selected patients (e.g., older or with

postural symptoms)• Identification of white coat hypertension/effect• Documentation of adherence• Monitoring of the response to therapy• Reinforcement of the importance of adherence, the importance of treatment, and

assistance with treatment to achieve BP target

Special Considerations in Treatment Recommendations

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IMPORTANT POINTS

• New guideline emphasize proper BP measurement and out‐of‐office BP measurement to confirm Dx

• Home BP monitors for most but may not be accurate for some patients• Consider 24‐ABP if data inconsistent• Risk vs. benefit of intensive BP reduction should be individualized

Initial therapy includes: • CCB, ACE/ARB, Thiazide DiureticsAdd‐on therapy: • Beta Blockers, Alpha Blockers• Mineralocorticoid Blockers, Direct vasodilators• Central acting drugs

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Notes

Documents

Shawna Nesbitt, MD...N Engl J Med. Nov 26; 2015 373(22):2103‐2116 SPRINT TRIAL: Systolic Blood Pressure Trend The SPRINT Research Group. N Engl J Med. 2015;373:2103‐2116 SPRINT