Heart Failure Prevention:

Hypertension Update

John MacKay, Pharm.D., BCPS

Providence St. Vincent Medical Center

Portland, Oregon

I have no financial relationships with commercial interests to

disclose

My presentation does not include discussion of off-label or

investigational use.

Disclosure Slide

Objectives

• Summarize the major recommendations of the American College of Cardiology-American Heart Association hypertension clinical practice guideline

• Review and interpret the evidence supporting the major changes to the guideline recommendations

• Apply these new recommendations to the management of patients with hypertension

Pre-assessment questions

1. A 56 year old previously healthy female presents to your clinic with an average blood pressure of 138/82 mm Hg on separate measurements 1 month apart. According to the American Heart Association and American College of Cardiology 2017 guideline, how would you classify her blood pressure?

a. Normal blood pressure

b. Prehypertension

c. Stage 1 hypertension

d. Stage 2 hypertension

2. Based on the current recommendations from the

American Heart Association and American College of

Cardiology, which of the following statements is/are true

regarding establishing a goal blood pressure goal of less

than 130/80 mmHg for patients with diabetes?

a. There is limited quality evidence to determine a

precise blood pressure target in adults with diabetes

b. The blood pressure goal is supported by several large

randomized, controlled clinical outcomes trials

targeting < 130/80 mmHg

c. There is consensus among the major guideline

documents over the last 15 years on the target blood

pressure for adult patients with diabetes

d. All of the above

3. Based on the ACC/AHA 2017 hypertension guideline,

the threshold blood pressure for beginning

pharmacologic treatment is ≥ 140/90 mmHg for which of

the following patient groups?

a. Patients with chronic kidney disease

b. Patients with no clinical cardiovascular disease and a

10-year ASCVD risk of less than 10%

c. Patients with diabetes

d. All of the above

4. Why is chlorthalidone considered a first line treatment

for hypertension?

a. Data from clinical trials such as ALLHAT demonstrate

chlorthalidone’s impact on cardiovascular outcomes

b. Chlorthalidone has a long half-life which in theory can

lead to less fluctuation and better BP control

throughout the dosing interval

c. Both A & B

d. None of the above, chlorthalidone should be reserved

for resistant hypertension only

American Heart AssociationHeart Disease and Stroke Statistics

2021 Update

0

20

40

60

80

100

120

140

Hypertension Diabetes Coronary Heart

Disease (CHD)

Stroke Heart Failure (HF)

121.5

35.4

20.1

7.6 6

126.9 million patients in the United States have

Cardiovascular Disease

Circulation 2021;143:e254-e743

Mil

lio

ns

of

pa

tie

nts

Lancet 2002;360:1903-1913

Establishing Blood Pressure Goals

• The risk of cardiovascular disease doubles for

every 20/10 mm Hg rise over 115/75 mm Hg

• Meta-analysis reviewing vascular mortality

and blood pressure

– 958,074 patients

• 11,960 deaths attributed to stroke

• 34,283 deaths attributed to ischemic heart disease

– Excluded studies enrolling patients with a history

of stroke or heart disease

Lancet 2002;360:1903-1913

Lancet 2002;360:1903-1913

Hypertension and Heart Failure

• 75% of patients who develop chronic heart

failure have hypertension

• Lifetime risk of heart failure is greater with

higher blood pressure compared to SBP < 120

mm Hg

– 1.6 for SBP 120-139 mm Hg

– 2.2 for SBP 140-159 mm Hg

– 2.6 for SBP 160 or greater

JACC 2016;68:1476–88; Heart 2011;97:1204-1211

Evolving Goal Blood Pressure

JNC 7

2003

JNC 8

2013

ESC

2013

Age < 60

< 140/90

< 140/90 < 140/90

Age ≥ 60 < 150/90

Age < 80< 150/90

< 140/90 (fit)

Age ≥ 80 < 150/90

Chronic kidney

disease< 130/80 < 140/90 < 140/90

Diabetes < 130/80 < 140/90 < 140/85

JAMA 2003;289:2560-2572;

JAMA 2014;311:507-520;

Eur Heart J 2013;34:2159–2219

JNC: Joint National Committee

ESC: European Society of Cardiology

Evolving Goal Blood Pressure

• Kidney Disease: Improving Global Outcomes

(KDIGO) 2012

– ≤ 130/80 for patients with chronic kidney disease

and urine albumin excretion > 30 mg/24 hours

• American Diabetes Association 2017

– < 140/90 for most patients (A)

– < 130/80 mmHg may be appropriate if high

cardiovascular risk (C)

KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney disease:

http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO_BP_GL.pdf,

Diabetes Care 2018;41(Suppl. 1):S86–S104

Published online November 13, 2017, available at: Hypertension

and Journal of the American College of Cardiology

JACC 2018;71:e127-248

Question

1

Is there evidence that self-directed monitoring of BP and/or

ambulatory BP monitoring are superior to office-based

measurement of BP by a healthcare worker for 1) preventing

adverse outcomes for which high BP is a risk factor and 2)

achieving better BP control?

2What is the optimal target for BP lowering during

antihypertensive therapy in adults?

3In adults with hypertension, do various antihypertensive drug

classes differ in their comparative benefits and harms?

4

In adults with hypertension, does initiating treatment with

antihypertensive pharmacological monotherapy versus

initiating treatment with 2 drugs (including fixed-dose

combination therapy), either of which may be followed by the

addition of sequential drugs, differ in comparative benefits

and/or harms on specific health outcomes?

BP: Blood pressure

Take Home Points

• < 130/80 mm Hg is the new < 140/90 mm Hg

• Use atherosclerotic risk estimation to guide decisions

• Measure blood pressure correctly

• Home/ambulatory blood pressure monitoring is in

• Beta-blockers are out (without a compelling indication), and most patients will need at least 2 drugs

Redefining Hypertension

CategorySystolic

blood pressure

Diastolic

blood pressure

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

JACC 2018;71:e127-248

Implications

NEJM 2018;378:497-498

Blood Pressure Thresholds and Goals

Clinical Condition(s)

BP

Threshold,

mm Hg

BP Goal,

mm Hg

General

Clinical CVD or 10-year ASCVD risk ≥10% ≥ 130/80 < 130/80

No clinical CVD and 10-year ASCVD risk <10% ≥ 140/90 < 130/80

Older persons (≥65 years of age; noninstitutionalized,

ambulatory, community-living adults)≥ 130 (SBP) < 130 (SBP)

Specific comorbidities

Diabetes mellitus ≥ 130/80 < 130/80

Chronic kidney disease ≥ 130/80 < 130/80

Chronic kidney disease after renal transplantation ≥ 130/80 < 130/80

Heart failure ≥ 130/80 < 130/80

Stable ischemic heart disease ≥ 130/80 < 130/80

Secondary stroke prevention ≥ 140/90 < 130/80

Secondary stroke prevention (lacunar) ≥ 130/80 < 130/80

Peripheral arterial disease ≥ 130/80 < 130/80

JACC 2018;71:e127-248

ACC/AHA Pooled Cohort Equations

http://tools.acc.org/ASCVD-Risk-Estimator-Plus/

Does targeting a systolic blood pressure

of less than 120 vs. less than 140 mm Hg

in patients with increased cardiovascular risk

but no diabetes improve cardiovascular

outcomes?

SPRINT

• Inclusion: 50 years old, baseline SBP 130 - 180 mmHg, and at least one of the following:– Clinical or subclinical cardiovascular disease other than

stroke

– CKD, defined as eGFR 20 - 59 ml/min/1.73m2

– Framingham Risk Score for 10-year CVD risk ≥ 15%

– Age >75 years

• Primary outcome: composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure or CV death

• Open-label, goal SBP < 120 mmHg or < 140 mmHg

NEJM 2015;73:2103-2116

SPRINT

• Medication choice

– ACE-inhibitors, ARBs, diuretics, calcium channel

blockers, beta-blockers, alpha-blockers

• Encouraged chlorthalidone as first line thiazide

• Encouraged amlodipine as the first line CCB

– Loop diuretics for chronic kidney disease

– Beta-blockers for patients with coronary artery disease

Baseline Characteristics

NEJM 2015;73:2103-2116

Treatment Group

Goal < 120

(n=4678)

Goal < 140

(n=4683)

Criteria for increased CV risk (%)

Age ≥ 75 years old

CKD

CV disease

Framingham 10-year CV risk 15% or greater

1317 (28.2%)

1330 (28.4%)

940 (20.1%)

20.1% ± 10.9

1319 (28.2%)

1316 (28.1%)

937 (20%)

20.1% ± 10.8

Age (mean) 67.9 67.9

Systolic BP (mean) 139.7 139.7

Diastolic BP (mean) 78.2 78

Mean eGFR in ml/min/m2 71.8 71.7

SPRINT Results

NEJM 2015;73:2103-2116

SPRINT Results

NEJM 2015;73:2103-2116

NEJM 2021;384:1921-1930

Endpoint

Treatment GroupHR

(95% CI)Goal < 120

(n=4678)

Goal < 140

(n=4683)

Primary endpoint

(number of patients, %)

264

(5.7%)

354

(7.6%)

0.73

(0.63-0.86)

Myocardial infarction102

(2.2%)

140

(3%)

0.72

(0.56-0.93)

Heart failure68

(1.5%)

105

(2.2%)

0.63

(0.46-0.86)

Cardiovascular death41

(0.9%)

71

(1.5%)

0.58

(0.39-0.84)

All cause mortality163

(3.5%)

215

(4.6%)

0.75

(0.61-0.92)

SPRINT Results

NEJM 2015;73:2103-2116

NEJM 2021;384:1921-1930

Endpoint

Treatment GroupHR

(95% CI)Goal < 120

(n=4678)

Goal < 140

(n=4683)

Patients with no CKD at baseline:

≥30% reduction in estimated GFR to <60

ml/min/1.73 m2

148

(3.8%)

41

(1.1%)

3.67

(2.62-5.26)

Hypotension99

(2.1%)

58

(1.3%)

1.71

(1.24-2.38)

Electrolyte abnormality138

(2.9%)

104

(2.2%)

1.33

(1.03-1.72)

Acute kidney injury193

(4.1%)

115

(2.5%)

1.69

(1.34-2.13)

Do the results of SPRINT apply to

elderly patients?

SPRINT: ≥ 75 Years Old

Endpoint

Treatment GroupHR

(95% CI)Goal < 120

(n=1317)

Goal < 140

(n=1319)

Primary endpoint

(number of patients, %)

102

(7.7%)

148

(11.2%)

0.6

(0.51-0.85)

Myocardial infarction37

(2.8%)

53

(4%)

0.69

(0.45-1.05)

Heart failure35

(2.7%)

56

(4.2%)

0.62

(0.4-0.95)

Cardiovascular death18

(1.4%)

29

(2.2%)

0.6

(0.33-1.09)

All cause mortality73

(5.5%)

107

(8.1%)

0.67

(0.49-0.91)

JAMA 2016;315:2673-2682

SPRINT: ≥ 75 Years Old

Endpoint

Treatment GroupHR

(95% CI)Goal < 120

(n=1317)

Goal < 140

(n=1319)

Serious adverse event637

(48.4%)

637

(48.3%)

0.99

(0.89-1.11)

Hypotension 2.4% 1.4%1.71

(0.97-3.09)

Syncope 3% 2.4%1.23

(0.76-2)

Electrolyte abnormalities 4% 2.7%1.51

(0.99-2.33)

Acute kidney injury or renal failure 5.5% 4%1.41

(0.98-2.04)

Fall Injury 4.9% 5.5%0.91

(0.65-1.29)

• 16 trials (52,235 patients) compared more versus less intensive BP lowering

• Mean follow-up of 3.7 years (minimum 6 months)

• Outcomes:

– Stroke; coronary death and nonfatal MI; hospitalization for heart failure; composite of the above events; CV death; and all-cause mortality

J Hypertens 2016; 34:613-22

Outcome

Systolic blood

pressure achieved

(mm Hg)

Trials RR (95% CI)

Absolute RR

1000

patients per

5 years

P-value

for trend

Stroke

140-149 vs. ≥ 150

130-139 vs. ≥ 140

< 130 vs. ≥ 130

8

15

7

0.68 (0.6-0.79)

0.62 (0.51-0.76)

0.71 (0.61-0.84)

-20

-16

-8

< 0.001

Coronary death,

nonfatal MI

140-149 vs. ≥ 150

130-139 vs. ≥ 140

< 130 vs. ≥ 130

8

16

8

0.81 (0.68-0.95)

0.77 (0.7-0.86)

0.86 (0.76-0.97)

-6

-8

-8

0.35

Heart failure

140-149 vs. ≥ 150

130-139 vs. ≥ 140

< 130 vs. ≥ 130

7

10

5

0.52 (0.41-0.65)

0.75 (0.35-1.59)

0.81 (0.51-1.3)

-25

-22

-16

0.11

CV death

140-149 vs. ≥ 150

130-139 vs. ≥ 140

< 130 vs. ≥ 130

8

16

9

0.79 (0.71-0.89)

0.77 (0.63-0.93)

0.8 (0.67-0.97)

-16

- 8

-5

0.001

All-cause

mortality

140-149 vs. ≥ 150

130-139 vs. ≥ 140

< 130 vs. ≥ 130

8

16

9

0.89(0.82-0.96)

0.83(0.72-0.96)

0.84(0.73-0.95)

-16

-10

-10

0.008

J Hypertens 2016; 34:613-22

Summary

• More intensive blood pressure lowering is

associated with better outcomes

– Meta-analyses support lower treated blood

pressure

– SPRINT supports targeting a systolic blood

pressure of < 120 mm Hg in patients with high

cardiovascular risk

Diabetes Target Blood Pressure

• ACCORD 2010

– Targeted SBP < 120 mm Hg versus < 140 mm Hg

– Lower incidence of non-fatal stroke, no difference in

nonfatal MI or CV death

• ADVANCE 2007

– ACE-inhibitor/diuretic combination versus placebo

– Suggested improvements in micro- and macrovascular

outcomes, all cause and CV mortality

– Patients eligible regardless of baseline BP

NEJM 2010;362:1575-1585Lancet 2007;37-:829-840

Antihypertensive Therapy Recommendations

• First line agents

– Thiazides, CCBs, ACE-I or ARB [Class I, LOE A-SR]

• Stage 1 (BP ≥ 130/80 mm Hg)

– ASCVD risk of < 10%:

• Non-pharmacologic therapy [Class I, LOE B-R)

– ASCVD risk of ≥ 10%:

• Antihypertensive monotherapy [Class IIa, LOE C-EO]

JACC 2018;71:e127-248

Antihypertensive Therapy Recommendations

• Stage 2 (BP ≥ 140/90 mm Hg)

– Combination pharmacologic therapy [Class I, LOE B-R]

– If BP is ≥ 140/90 mm Hg and an average >20/10 mm

Hg above goal:

• Start with 2 antihypertensive medications, separate

medications or fixed dose combinations [Class I, LOE C-EO]

• Special Population based recommendations

– Black: CCB or thiazide-type diuretic

– Pregnancy: methyldopa, nifedipine, and/or labetalol

JACC 2018;71:e127-248

Pharmacotherapy 2007;27:1322-1333

Selecting the Appropriate Agent

Compelling IndicationsClinical Condition First Line Drug

Diabetes Mellitus Thiazide, CCB, ACE-I or ARB

Diabetes Mellitus with albuminuria ACE-I or ARB

Chronic kidney disease (Stage 3 or higher or

stage 1 or 2 with albuminuria)ACE-I or ARB

Heart failure with reduced ejection fraction Beta-blocker, ACE-I or ARB, ARA

Heart failure with preserved ejection fraction Beta-blocker, ACE-I or ARB

Stable ischemic heart disease Beta-blocker, ACE-I or ARB

Stable ischemic heart disease with angina Beta-blocker, CCB

Secondary stroke prevention Thiazide, ACE-I or ARB

JACC 2018;71:e127-248

Thiazide-like Diuretics

Drug PK MOA Side Effects MonitoringCIs/

Precaution

Chlorthalidone

Half-Life:

40-60 hours

Metabolism:

hepatic

Inhibits

sodium and

chloride

reabsorption

in the distal

tubule

Hypokalemia

Photosensitivity

BP

Electrolytes

Renal

function

Severe

sulfa

allergy,

AnuriaHydrochlorothiazide

Half-Life:

6-15 hours

Not

metabolized

40

Calcium Channel Blockers

Drug PK MOASide

EffectsMonitoring

Contraindications

/ Precautions

Amlodipine

Half-Life:

30-60 hours

Metabolism:

liver

Inhibits calcium

from entering

vascular smooth

muscle causing

relaxation and

peripheral

vasodilation

Peripheral

edema,

fatigue,

headache

Heart Rate,

BP, edema

Hypersensitivity

to amlodipine

Diltiazem ER

Half-Life: 5-10

hours

Metabolism:

liver

Non-DH CCB:

Inhibits calcium

from entering

vascular smooth

muscle causing

relaxation and

coronary

vasodilation

Peripheral

edema,

dizziness,

fatigue

LFTs, BP,

EKG, and HR

Sick sinus

syndrome, 2nd or

3rd degree AV

block, severe

hypotension,

acute MI,

pulmonary edema

41

ACE-Inhibitors

Drug PK MOA Side Effects MonitoringCIs/

Precautions

Lisinopril

Half-Life:

11-12 hours

Not

metabolized

Prevents

conversion of

angiotensin I to

angiotensin II

leading to

increased renin

activity and

decreased

aldosterone

secretion

Syncope

Hyperkalemia

Cough

Angioedema

Acute ↑ SCr

Potassium

Renal

function

Angioedema

related to

previous ACEI

Concomitant

use with

aliskiren in

patients with

DM

Captopril

Half-Life:

< 3 hours

Renal

excretion

Enalapril

Half-Life:

2 hours

Prodrug

42

ARB

Drug PK MOA Side Effects Monitoring

CIs/

Precautions

Losartan

Half-Life:

1.5-2 hours

Metabolism:

liver

Reversible,

non-

competitive

angiotensin II

receptor

antagonist

Chest pain

Hypotension

Hyperkalemia

Hypoglycemia

Diarrhea

Anemia

BP

Electrolytes

Renal

Function

Concomitant

use with

aliskiren in

patients with

DM

Candesartan

Half-Life:

5-9 hours

Metabolism:

bioactivated

during

absorption

Valsartan

Half-Life:

6 hours

Metabolism:

not identified

When should home/ambulatory blood

pressure monitoring be incorporated

into a treatment plan for hypertension?

Ambulatory BP monitoring

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, in conjunction with telehealth

counseling or clinical interventions.

JACC 2018;71:e127-248

Corresponding Blood Pressure

Measurements

Clinic HBPMDaytime

ABPM

Nighttime

ABPM

24-Hour

ABPM

120/80 120/80 120/80 100/65 115/75

130/80 130/80 130/80 110/65 125/75

140/90 135/85 135/85 120/70 130/80

160/100 145/90 145/90 140/85 145/90

HBPM: home blood pressure monitoring

ABPM: ambulatory blood pressure monitoring

White Coat Versus Masked Hypertension

JACC 2018;71:e127-248

CVD Risk Factors Common in Patients With Hypertension

Modifiable Risk

Factors

Relatively Fixed Risk

Factors

• Active smoking,

secondhand smoke

• Diabetes mellitus

• Dyslipidemia/

hypercholesterolemia

• Overweight/obesity

• Physical inactivity/low

fitness

• Unhealthy diet

• CKD

• Family history

• Increased age

• Low socioeconomic/

educational status

• Male sex

• Obstructive sleep apnea

• Psychosocial stress

Nonpharmacologic Interventions (Class I, LOE A)

Intervention DescriptionApproximate effect on SBP

in hypertensive patient

Weight lossRecommended for overweight or

obese patients-5 mm Hg

Healthy Diet

Diet rich in fruits, vegetables, whole

grains, low-fat dairy; reduced saturate

and total fat

-11 mm Hg

Reduced dietary

sodiumOptimal goal < 1500 mg/day -5 to -6 mm Hg

Enhanced dietary

potassiumGoal 3500-5000 mg/day -4 to -5 mm Hg

Physical activity

Structured exercise program

(dynamic/isometric resistance,

aerobic)

-5 to -8 mm Hg

Moderate alcohol

intake

Men: ≤ 2 per day

Women: ≤ 1 per day-4 mm Hg

JACC 2018;71:e127-248

Summary

• < 130/80 mm Hg is the treatment goal and

threshold for the majority of patients

– Healthy lifestyle interventions are the cornerstone

of therapy

• First-line medications are ACE-inhibitors, ARB,

CCB or thiazides

• Combination therapy is required for most

patients

Post-assessment questions

1. A 56 year old previously healthy female presents to your clinic with an average blood pressure of 138/82 mm Hg on separate measurements 1 month apart. According to the American Heart Association and American College of Cardiology 2017 guideline, how would you classify her blood pressure?

a. Normal blood pressure

b. Prehypertension

c. Stage 1 hypertension

d. Stage 2 hypertension

2. Based on the current recommendations from the

American Heart Association and American College of

Cardiology, which of the following statements is/are true

regarding establishing a goal blood pressure goal of less

than 130/80 mmHg for patients with diabetes?

a. There is limited quality evidence to determine a

precise blood pressure target in adults with diabetes

b. The blood pressure goal is supported by several large

randomized, controlled clinical outcomes trials

targeting < 130/80 mmHg

c. There is consensus among the major guideline

documents over the last 15 years on the target blood

pressure for adult patients with diabetes

d. All of the above

3. Based on the ACC/AHA 2017 hypertension guideline,

the threshold blood pressure for beginning

pharmacologic treatment is ≥ 140/90 mmHg for which of

the following patient groups?

a. Patients with chronic kidney disease

b. Patients with no clinical cardiovascular disease and a

10-year ASCVD risk of less than 10%

c. Patients with diabetes

d. All of the above

4. Why is chlorthalidone considered a first line treatment

for hypertension?

a. Data from clinical trials such as ALLHAT demonstrate

chlorthalidone’s impact on cardiovascular outcomes

b. Chlorthalidone has a long half-life which in theory can

lead to less fluctuation and better BP control

throughout the dosing interval

c. Both A & B

d. None of the above, chlorthalidone should be reserved

for resistant hypertension only

Heart Failure Prevention:

Hypertension Update

John MacKay, Pharm.D., BCPS

Providence St. Vincent Medical Center

Portland, Oregon