3 acc prevention blood pressure

The Evidence for Current Cardiovascular Disease

Prevention Guidelines:

Blood Pressure Control Evidence and Guidelines

American College of Cardiology Best Practice Quality Initiative Subcommittee

and Prevention Committee

Classification of Classification of Recommendations and Levels Recommendations and Levels of Evidenceof Evidence

*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.

†In 2003, the ACC/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline recommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart from the rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this will increase readers’ comprehension of the guidelines and will allow queries at the individual recommendation level.

I IIa IIb III

I IIa IIb III

I IIa IIb III

I IIa IIb III I IIa IIb III

I IIa IIb III

I IIa IIb III

I IIa IIb III

I IIa IIb III

I IIa IIb III

I IIa IIb III

I IIa IIb III

Icons Representing the Classification and Icons Representing the Classification and Evidence Levels for RecommendationsEvidence Levels for Recommendations

Blood Pressure EvidenceBlood Pressure Evidence

Evidence for Current Cardiovascular Evidence for Current Cardiovascular DiseaseDisease

Prevention GuidelinesPrevention Guidelines

Hypert

ensi

on*

Pre

vale

nce

(%

)

18-29

National Health and Nutrition Examination Survey (NHANES) III

30-39 40-49 50-59 60-69 70-79 80+

Age

3%9%

18%

Source: JNC-VI. Arch Intern Med 1997;157:2413-2446

51%

66%72%

38%

*Hypertension defined as blood pressure >140/90 mmHg or treatment

High Blood Pressure*: High Blood Pressure*: Prevalence Increases Prevalence Increases with Agewith Age

The prevalence of high blood pressure increases with age

High Blood Pressure*: High Blood Pressure*: Prevalence in Different Patient GroupsPrevalence in Different Patient Groups

National Health and Nutrition Examination Survey (NHANES)

Source: Yoon SS et al. NCHS Data Brief 2012;107:1-7

*High blood pressure defined as blood pressure 140/90 mmHg or treatment

Ris

k of

hyp

erte

nsio

n (%

)

*Residual lifetime risk of developing hypertension among people with blood pressure <140/90 mmHg starting at age 55-65 years

Years

Men Women

Source: Vasan RS et al. JAMA 2002; 287:1003-1010

Framingham Heart Study

High Blood Pressure: High Blood Pressure: Lifetime Risk*Lifetime Risk*

National Health and Nutrition Examination Survey (NHANES)

Bloo

d pr

essu

reag

e-ad

just

ed p

erce

ntag

e

Change in Blood Pressure Change in Blood Pressure Levels in the United States Levels in the United States Over TimeOver Time

Source: Ford ES et al. Figure 2b, Circulation 2009;120:1181-1188

Blood Pressure Treatment Blood Pressure Treatment Evidence and GuidelinesEvidence and Guidelines



Provides information on response to treatment. May help improve adherence to treatment and evaluate “white-coat” HTN

Self-measurement

Indicated for evaluation of “white-coat” HTN. Absence of 10–20% BP decrease during sleep indicates increased CVD risk

Ambulatory BP monitoring

Two readings, 5 minutes apart, sitting in chair

Confirm elevated reading in contralateral arm

In-office

BP=Blood pressure, CVD=Cardiovascular disease, HTN=Hypertension

Source: Chobanian AV et al. JAMA 2003;289:2560-2572

JNC VII Guidelines: JNC VII Guidelines: Measurement of Blood Measurement of Blood PressurePressure Method Brief Description

Medical Conditions

Chronic kidney disease

Primary hyperaldosteronism

Renovascular disease

Chronic steroid therapy

Cushing’s syndrome

Pheochromocytoma

Aortic coarctation

Thyroid or parathyroid disease

Sleep apnea

Drugs

NSAIDs

Oral contraceptives

Adrenal steroids

Sympathomimetics

Cyclosporine or tacrolimus

Erythropoietin

Ephedra, mu huang, bitter orange

Cocaine or amphetamines

Alcohol


NSAIDs=Non-steroidal anti-inflammatory drugs

JNC VII Guidelines: JNC VII Guidelines: Causes of Secondary Causes of Secondary HypertensionHypertension

Source: Calhoun DA et al. Circulation 2008;117:e510-526

Diagnostic and Treatment Algorithm

Confirm Treatment Resistance Confirm Treatment Resistance

Office BP >140/90 or 130/80 mm Hg in patients with DM or chronic kidney disease

andPatient prescribed 3 or more antihypertensive

medications at optimal doses, including if possible a diuretic

orOffice BP at goal but patient requiring 4 or more

antihypertensive medications

Exclude Pseudoresistance Exclude Pseudoresistance

Is patient adherent with prescribed reigmen?

Obtain home, work, or ambulatory BP readings to exclude white coat effect

Identify/Reverse Contributing Lifestyle Factors

Identify/Reverse Contributing Lifestyle Factors

ObesityPhysical inactivity

Excessive alcohol ingestionHigh salt, low fiber diet

BP=Blood pressure, DM=Diabetes mellitus

Discontinue/Minimize Interfering Substances

Discontinue/Minimize Interfering Substances

Non-steroidal anti-inflammatory agentsSympathomimetics (diet pills, decongestants)

StimulantsOral contraceptives

LicoriceEphedra

Resistant HypertensionResistant Hypertension

Diagnostic and Treatment Algorithm

Screen for Secondary Causes of Hypertension

Screen for Secondary Causes of Hypertension

Obstructive sleep apnea (snoring, witnessed apena, excessive daytime sleepiness)

Primary aldosteronism (elevated aldosterone/renin ratio)

Chronic kidney disease (CrCl <30 ml/min)Renal artery stenosis (young female, known

atherosclerotic disease, worsening renal function)Pheochromocytoma (episodic hypertension,

palpitations, diaphoresis, headache)Cushing’s syndrome (moon facies, central obesity,

abdominal striae, inter-scapular fat deposition)Aortic coarctation (differential in brachial or

femoral pulses, systolic bruit)

Pharmacologic TreatmentPharmacologic Treatment

Maximize diuretic therapy, including possible addition of mineralocorticoid receptor antagonist

Combine agents with different mechanisms of actionUse loop diuretics in patients with chronic kidney

disease and/or those receiving potent vasodilators (e.g., minoxidil)

Refer to SpecialistRefer to Specialist

Refer to appropriate specialist for known or suspected secondary cause(s) of hypertension

Refer to hypertension specialist if blood pressure remains uncontrolled after 6 months of treatment

Resistant Hypertension (Continued)Resistant Hypertension (Continued)

Source: Calhoun DA et al. Circulation 2008;117:e510-526

CrCl=Creatinine clearance

Source: Prospective Studies Collaboration. Lancet 2002;360:1903-1913

Usual Diastolic BP (mm Hg)Usual Systolic BP (mm Hg)

Isch

em

ic H

eart

Dis

ease

M

ort

alit

y(F

loati

ng a

bso

lute

ris

k)

50-59

60-69

70-79

80-89

Age at Risk (Y)

40-49

256

128

64

32

16

8

4

2

1

0120 140 160 180

50-59

60-69

70-79

80-89

Age at Risk (Y)

40-49

256

128

64

32

16

8

4

2

1

080 90 100 11070

Isch

em

ic H

eart

Dis

ease

M

ort

alit

y(F

loati

ng a

bso

lute

ris

k)

Ischemic heart disease mortality and blood pressure

BP=Blood pressure

High Blood Pressure Evidence: High Blood Pressure Evidence: Increased Risk with Increased Risk with Increased LevelsIncreased Levels

Veterans Administration, 1967

Veterans Administration, 1970

Hypertension Stroke Study, 1974

USPHS Study, 1977

EWPHE Study, 1985

Coope and Warrender, 1986

SHEP Study, 1991

STOP-Hypertension Study, 1991

MRC Study, 1992

Syst-Eur Study, 1997

Total0 0.5 1.0 1.5 2.0

0.79 (0.69 to 0.90)

Source: He J et al. Am Heart J 1999;138:211-219

Better than placebo Worse than placebo

CHD=Coronary heart disease

High Blood Pressure Evidence: High Blood Pressure Evidence: Risk of CHD with Risk of CHD with TreatmentTreatment

Source: Abbott K et al. J Clin Pharmacology 2004;44:431-438

Trial (SBP Achieved)

1 1.5 2 2.5 3 3.5 4

AASK (127 mm Hg)

HOT (138 mm Hg)

MDRD (132 mm Hg)

ABCD (127 mm Hg)

UKPDS (144 mm Hg)

Number of BP Meds

AASK=African American Study of Kidney Disease and Hypertension, ABCD=Appropriate Blood Pressure Control in Diabetes, BP=Blood pressure,

HOT=Hypertension Optimal Treatment, MDRD=Modification of Dietary Protein in Renal Disease, SBP=Systolic blood pressure, UKPDS=UK Prospective Diabetes Study

High Blood Pressure Evidence: High Blood Pressure Evidence: Number of Number of Medications NeededMedications Needed

33,357 patients with HTN and >1 CHD risk factor randomized to chlorthalidone, amlodipine, or lisinopril for 5 years

All three BP lowering agents provide similar efficacy

0 1 2 3 4 5 6 70

.04

.08

.12

.16

.20

Rate

of

MI

or

fata

l C

HD

Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Source: ALLHAT Investigators. JAMA 2002;288:2981-2997

Years to CHD Event

BP=Blood pressure, CHD=Coronary heart disease, HTN=Hypertension, MI=Myocardial infarction

ChlorthalidoneAmlodipineLisinopril

RR (95% CI) P-value

A/C 0.98

(0.90-1.07)

0.65

L/C 0.99

(0.91-1.08)

0.81

Blood Pressure Lowering Therapy Blood Pressure Lowering Therapy Evidence: Primary Evidence: Primary PreventionPrevention

Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension Study

Source: Dahlöf B et al. Lancet 2002;359:995-1003

ARB=Angiotensin receptor blocker, CV=Cardiovascular, DBP=Diastolic blood pressure, LVH=Left ventricular hypertrophy,

MI=Myocardial infarction, SBP=Systolic blood pressure

*Defined by SBP=160-200 mmHg or DBP=95-115 mmHg

0 6 12 18 24 30 36 42 48 54 60 66

Study Month

4

8

12

16

0Pro

port

ion w

ith C

V

death

, M

I, o

r st

roke

(%

) Atenolol

13% RRR, P=0.021

LosartanLosartan


9,193 high-risk hypertensive* patients with LVH randomized to losartan (100 mg) or atenolol (100 mg) for 5 years

An ARB provides greater efficacy in patients with LVH

19,342 high-risk hypertensive patients with 3 additional CV risk factors randomized to amlodipine (10 mg) & perindopril (8 mg) or atenolol (100 mg) & bendroflumethiazide (2.5 mg) for 5.5 years

Both BP lowering regimens provide similar efficacy

Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA)

Nonfa

tal M

I and f

ata

l C

HD

(%

)

6

2

4

01 2 3 4 5 60

Time since randomization (years)

RRR=10%, P=0.1052

Atenolol-based regimen

Amlodipine-based regimen


BP=Blood pressure, CV=Cardiovascular, CHD=Coronary heart disease, MI=Myocardial infarction


Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA)

Secondary endpointsNonfatal MI + fatal CHD 7.4 8.5Total coronary endpoint 14.6 16.8Total CV events/procedures 27.4 32.8 All-cause mortality 13.9 15.5 CV mortality 4.9 6.5 Fatal/nonfatal stroke 6.2 8.1 Fatal/nonfatal HF 2.5 3.0

Amlodipine-based

rate/1000patient years

<0.05<0.01

<0.0001

<0.05 0.001

<0.001 NS

P

Amlodipine-based better

Atenolol-based better

0.50 0.70 1.00 1.45 2.00

Atenolol-based

rate/1000patient years


CHD=Coronary heart disease, CV=Cardiovascular, HF=Heart failure, MI=Myocardial infarction

An amlodopine-based regimen appears to reduce the rate of other CV events


11,506 high-risk hypertensive patients randomized to benazepril (40 mg) and amlodipine (10 mg) or benazepril (40 mg) and HCTZ (25

mg) for 36 months*

An amlodipine-based regimen provides greater benefit

Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension

(ACCOMPLISH)

Benazepril/HCTZ

Benazepril/Amlodipine

Com

posi

te o

f C

V d

eath

, M

I, s

troke

, hosp

italiz

ati

on f

or

angin

a, su

dden c

ard

iac

arr

est

, and c

oro

nary

re

vasc

ula

riza

tion (

%)

20% RRR, HR=0.80, P=0.0002

Source: Jamerson K et al. NEJM 2008;359:2417-2428

0.16

0.14

0.12

0.10

0.08

0.06

0.04

0.02

0.000 200 400 600 800 1000 1200 1400

*The study was prematurely stopped


CV=Cardiovascular, MI=Myocardial infarction

3,845 patients >80 years with SBP >160 mm Hg randomized to treatment to indapamide (1.5 mg) and perindopril (2-4 mg if needed)

vs. placebo for 2 years

Blood pressure control in patients >80 years of age provides benefit

Hypertension in the Very Elderly (HYVET) Trial

Source: Beckett NS et al. NEJM 2008;358:1887-1898

CV=Cardiovascular, CVA=Cerebrovascular accident

Rate

/100

0 pa

tient

yea

rs (%

)

P=0.06 P=0.05

P=0.02

P<0.001

P<0.001

(Primary end point)


Indapamide + perindopril

Placebo

22,576 patients with HTN and CAD randomized to a BP lowering strategy with verapamil SR (240 mg) or atenolol (50

mg) for 2.7 years

Both a CAS and NCAS provide similar efficacy

0 6 12 18 24 36 48 5442 6030

International Verapamil-Trandolapril Study (INVEST)

Months

RR=0.98, P=0.57

Calcium antagonist strategy (CAS)*Non-calcium antagonist strategy (NCAS)*

Source: Pepine CJ et al. JAMA 2003;290:2805-2816

*Trandolapril (up to 4 mg) was added in those with diabetes mellitus, chronic kidney disease, or heart failure

Inci

dence

of a

ll ca

use

deat

h, n

onfa

tal M

I, or

no

nfat

al s

trok

e

BP=Blood pressure, CAS=Calcium antagonist strategy, HTN=Hypertension, MI=Myocardial infarction, NCAS=Non-calcium antagonist strategy

Blood Pressure Lowering Therapy Blood Pressure Lowering Therapy Evidence: Secondary Evidence: Secondary PreventionPrevention

0

20

10

15

5

Favors valsartan Favors amlodipine

Primary cardiac composite endpointCardiac mortalityCardiac morbidity

All myocardial infarctionAll congestive heart failureAll strokeAll-cause deathNew-onset diabetes

0.5 1 2

Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) Trial

Source: Julius S et al. Lancet 2004;363:2022-2031

BP=Blood pressure, CV=Cardiovascular, HTN=Hypertension

15,245 patients with untreated HTN and high CV risk randomized to a BP

lowering strategy with valsartan (160 mg) or amlodipine (10 mg) for 4.2 years

Both blood pressure lowering regimens provide similar efficacy


Source: Nissen S et al. JAMA 2004;292:2217-2226

Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) Trial

*Includes CV death, myocardial infarction, cardiac arrest, coronary revascularization, hospitalization for heart failure or angina pectoris, stroke,

transient ischemic attack, development of peripheral arterial disease

CV

eve

nt r

ate*

0

0.25

0.20

0.10

0.05

6 12 18 24

0.15

0

Placebo

AmlodipineEnalapril

Months

Follow-up BP (mmHg)

125/77124/77130/78

BP=Blood pressure, CAD=Coronary artery disease, CV=Cardiovascular, DBP=Diastolic blood pressure

1,991 patients with CAD and a DBP <100 mmHg randomized to amlodipine (10 mg), enalapril (20 mg), or placebo for 2 years

Treatment with amlodipine results in reduced CV events


Source: Hansson L et al. Lancet 1998;351:1755-1762

Hypertension Optimal Treatment (HOT) Study

Diastolic BP goal

Patients without Diabetes

Majo

r C

V e

vents

per

100

0 p

ati

ent-

years

Patients with Diabetes

Diastolic BP goal

18,790 patients with a baseline diastolic BP of 100-115 mm Hg randomized to a target diastolic BP of <90 mm Hg, <85 mm Hg,

or <80 mm Hg

More intensive blood pressure control provides greater benefit in diabetics

Blood Pressure Lowering Therapy Blood Pressure Lowering Therapy Evidence: Effect of Intensive Evidence: Effect of Intensive Blood Pressure ControlBlood Pressure Control

BP=Blood pressure, CV=Cardiovascular

Source: Verdecchia P et al. Lancet 2009;374:525-533 Source: Verdecchia P et al. Lancet 2009;374:525-533

Cardio-SIS Trial

AF=Atrial fibrillation, ESRD=End stage renal disease, CHF=Congestive heart failure, CVA=Cerebrovascular accident, LVH=Left ventricular hypertrophy, MI=Myocardial infarction,

PAD=Peripheral artery disease, SBP=Systolic blood pressure, TIA=Transient ischemic attack

AF=Atrial fibrillation, ESRD=End stage renal disease, CHF=Congestive heart failure, CVA=Cerebrovascular accident, LVH=Left ventricular hypertrophy, MI=Myocardial infarction,

PAD=Peripheral artery disease, SBP=Systolic blood pressure, TIA=Transient ischemic attack

Inci

dence

of

LVH

(%

)

Usual Control

17.0

Tight Control

21

14

7

0

11.4

P=0.013

Com

posi

te o

f C

V

events

* (%

)Usual Control

9.4

Tight Control

15

10

5

0

4.8

P=0.003

*Composite of death, MI, CVA, TIA, CHF, angina, new AF, revascularization, aortic dissection, PAD, and ESRD

*Composite of death, MI, CVA, TIA, CHF, angina, new AF, revascularization, aortic dissection, PAD, and ESRD

1,111 patients >55 years with SBP >150 mm Hg randomized to treatment to achieve usual BP control (SBP <140 mm Hg)

or intensive BP control (SBP <130 mm Hg)

More intensive blood pressure control provides greater benefit


HR=1.15, p=0.036

International Verapamil-Trandolapril Study (INVEST)—DM Substudy

BP=Blood pressure, CV=Cardiovascular


Source: Cooper-DeHoff RM et al. JAMA 2010;304:61-68

6,400 diabetic patients from the INVEST study grouped by tight (<130 mm Hg), usual (>130 to <140 mm Hg), or uncontrolled (>140

mm Hg) blood pressure

Tight BP control is not associated with reduced adverse CV events

Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial

Pat

ien

ts w

ith

Eve

nts

(%

)

0

5

10

15

20

Years Post-Randomization0 1 2 3 4 5 6 7 8

Pat

ien

ts w

ith

Eve

nts

(%

)

0

5

10

15

20

Years Post-Randomization0 1 2 3 4 5 6 7 8

Tota

l st

roke

HR=0.8895% CI (0.73-1.06)

HR=0.5995% CI (0.39-0.89)

Nonfa

tal M

I, n

onfa

tal

stro

ke, or

CV

death

BP=Blood pressure, DM=Diabetes mellitus, HR=Hazard ratio, SBP=Systolic blood pressure

ACCORD study group. NEJM 2010;362:1575-1585

4,733 diabetic patients randomized to intensive BP control (target SBP <120 mm Hg) or standard BP control (target SBP <140 mm

Hg) for 4.7 years

Intensive BP control in DM does not reduce a composite of adverse CV events, but does reduce the rate of stroke


2-drug combination for most† (usually thiazide-type diuretic and ACE-I or ARB or BB or CCB).

Yes >100 >160 Stage 2 Hypertension

Drug(s) for compelling indications.‡

Other antihypertensive drugs (as needed).

Thiazide-type diuretics for most. May consider ACE-I, ARB, BB, CCB, or combination of these.

Yes 90–99 140–159

Stage 1 Hypertension

Drug(s) for compelling indications.‡

No antihypertensive drug indicated.

Yes 80–89 120–139

Prehypertension

Encourage <80 <120 Normal

With compelling indications

Without compelling indications

Initial drug therapy Lifestyle

modification

DBP* mmHg

SBP* mmHg

BP classification

and

or

or

or


ACE-I=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=Beta-blocker, BP=Blood pressure, CCB=Calcium channel blocker, DBP=Diastolic blood pressure, SBP=Systolic blood pressure

*Treatment determined by highest blood pressure category†Initial combined therapy should be used cautiously

in those at risk for orthostatic hypotension‡Treat patients with chronic kidney disease or diabetes mellitus

to blood pressure goal of <130/80 mmHg

JNC VII Guidelines: JNC VII Guidelines: Management and TreatmentManagement and Treatment

Modification Recommendation Approximate SBP Reduction Range

Weight reduction Maintain normal body weight (BMI=18.5-25)

5-20 mmHg/10 kg weight lost

DASH eating plan

Diet rich in fruits, vegetables, low fat dairy and reduced in fat

8-14 mmHg

Restrict sodium intake

<2.4 grams of sodium per day 2-8 mmHg

Physical activity Regular aerobic exercise for at least 30 minutes most days of the week

4-10 mmHg

Moderate alcohol <2 drinks/day for men and <1 drink/day for women

2-4 mmHg


BMI=Body mass index, BP=Blood pressure, SBP=Systolic blood pressure

JNC VII Guidelines: JNC VII Guidelines: Lifestyle Modifications for BP Lifestyle Modifications for BP ControlControl

Clinical-Trial BasisCompelling Indication

ALLHAT, HOPE, ANBP2,LIFE, CONVINCE

High CAD Risk

ACC/AHA Post-MI Guidelines, BHAT, SAVE, Capricorn,

EPHESUS

Post-MI

MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, Val-HeFT,

RALES

Initial Therapy Options

Diuretic, BB, ACE-I, CCB

BB, ACE-I, Aldo ANT

Diuretic, BB, ACE-I,ARB, Aldo ANT

Heart Failure

Recurrent Stroke Prevention

PROGRESSDiuretic, ACE-I

NKF-ADA Guideline,UKPDS, ALLHAT

NKF Guidelines, Captopril Trial, RENAAL, IDNT, REIN,

AASK

Diuretic, BB, ACE-I,ARB, CCB

ACE-I, ARB

Diabetes Mellitus

Chronic Kidney Disease


ACE-I=Angiotensin converting enzyme inhibitor, Aldo ANT=Aldosterone antagonist, ARB=Angiotensin receptor blocker, BB=Beta-blocker, CAD=Coronary

artery disease, CCB=Calcium channel blocker, MI=Myocardial infarction

JNC VII Guidelines: JNC VII Guidelines: Compelling Indications for Drug Compelling Indications for Drug ClassesClasses

Optimize dosages or add additional drugs until goal BP is achieved.Consider consultation with hypertension specialist.

Lifestyle modifications

Initial drug choices

Not at goal BP

Not at goal BP (<140/90 mm Hg)(<130/80 mm Hg for those with diabetes mellitus

or chronic kidney disease)

WITH compelling indicationsWITHOUT compelling indications

Stage 1 hypertension(SBP 140–159 mm Hg or DBP 90–99 mm Hg):

Thiazide-type diuretic for most.May consider ACEI, ARB, BB, CCB, or combo.

Stage 2 hypertension(SBP 160 or DBP 100 mm Hg):

Two-drug combination for most (usually thiazide-type diuretic and

ACEI or ARB or BB or CCB).

Drugs for compelling indications:

Other antihypertensive drugs (diuretic, ACEI, ARB, BB, CCB)

as needed.


ACEI=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=Beta-blocker, BP=Blood pressure, CCB=Calcium channel blocker,

DBP=Diastolic blood pressure, SBP=Systolic blood pressure

JNC VII Guidelines:JNC VII Guidelines:Blood Pressure Treatment Blood Pressure Treatment AlgorithmAlgorithm

Counsel regarding the need for lifestyle modification: weight control; increased physical activity; alcohol moderation; sodium reduction; and emphasis on increased consumption of fresh fruits, vegetables, and low-fat dairy products.

Source: Smith SC Jr. et al. JACC 2011;58:2432-2446

I IIa IIb III

Blood Pressure RecommendationsBlood Pressure Recommendations

Primary and Secondary Prevention

Source: Buse JB et al. Circulation 2007;115:114-126

• BP should be measured at every routine visit. Patients with a SBP >130 mm Hg or DBP >80 mm Hg should have BP confirmed on a separate day.

• Patients should be treated to a SBP <130 mm Hg and a DBP <80 mm Hg.

• Patients with a SBP of 130-139 mm Hg or a DBP of 80-89 mm Hg should initiate lifestyle modification* alone for a maximum of 3 months. If, after these efforts, targets are not achieved, treatment with pharmacological agents should be initiated.

*Includes weight control, increased physical activity, alcohol moderation, sodium reduction, and emphasis on increased consumption of fresh fruits, vegetables, and low-fat dairy products

AHA=American Heart Association, BP=Blood pressure, CV=Cardiovascular, DBP=Diastolic blood pressure,

DM=Diabetes mellitus, SBP=Systolic blood pressure

AHA Primary Prevention of CV Disease in AHA Primary Prevention of CV Disease in DMDMBlood Pressure RecommendationsBlood Pressure RecommendationsPrimary Prevention


• Multiple-drug therapy is generally required to achieve BP targets.

• In elderly hypertensive patients, BP should be lowered gradually to avoid complications.

• Orthostatic measurement of BP should be performed when clinically indicated.

• Patients not achieving target BP despite multiple-drug therapy should be referred to a physician specializing in the care of patients with hypertension.

AHA=American Heart Association, BP=Blood pressure, CV=Cardiovascular, DM=Diabetes Mellitus

AHA Primary Prevention of CV Disease in AHA Primary Prevention of CV Disease in DMDMBlood Pressure Recommendations Blood Pressure Recommendations (Continued)(Continued)

Primary Prevention

• BP should be measured at every routine DM visit. Patients found to have a SBP >130 mm Hg or a DBP >80 mm Hg should have BP confirmed on a separate day. A repeat SBP >130 mm Hg or a repeat DBP >80 mm Hg confirms a diagnosis of hypertension.

• Patients with DM should be treated to a SBP <130 mm Hg.

• Patients with DM should be treated to a DBP <80 mm Hg.

• Patients with a SBP 130-139 mm Hg or a DBP 80-89 mm Hg may be given lifestyle therapy alone for a maximum of 3 months, and then if targets are not achieved, patients should have pharmacologic agents added.

Source: American Diabetes Association. Diabetes Care 2010;33:S11-61

ADA=American Diabetes Association, BP=Blood pressure, DBP=Diastolic blood pressure, DM=Diabetes mellitus, SBP=Systolic blood pressure

ADA Blood Pressure RecommendationsADA Blood Pressure Recommendationsfor Patients with Diabetes Mellitusfor Patients with Diabetes Mellitus

Primary Prevention

• Patients with more severe hypertension (SBP >140 mm Hg or DBP >90 mm Hg) at diagnosis or follow-up should receive pharmacologic therapy in addition to lifestyle therapy.

• Lifestyle therapy for hypertension consists of weight loss if overweight, DASH-style dietary pattern including reducing sodium and increasing potassium intake, moderation of alcohol intake, and increased physical activity.


ACE=Angiotensin converting enzyme, ADA=American Diabetes Association, BP=Blood pressure, DBP=Diastolic blood pressure, DM=Diabetes mellitus,

GFR=Glomerular filtration rate, SBP=Systolic blood pressure

ADA Blood Pressure RecommendationsADA Blood Pressure Recommendationsfor Patients with Diabetes Mellitus for Patients with Diabetes Mellitus (Continued)(Continued) Primary Prevention

• Pharmacologic therapy for patients with DM and hypertension should be paired with a regimen that includes either an ACE inhibitor or an ARB. If one class is not tolerated, the other should be substituted. If needed to achieve BP targets, a thiazide diuretic should be added to those with an estimated GFR >30 ml/min and a loop diuretic with an estimated GFR <30 ml/min.

• Multiple drug therapy (two or more agents at maximal doses) is generally required to achieve BP targets.


ACE=Angiotensin converting enzyme, ADA=American Diabetes Association, ARB=Angiotensin receptor blocker, BP=Blood pressure,

DM=Diabetes mellitus, GFR=Glomerular filtrate rate


Use of an ACE inhibitor and/or beta-blocker in those with BP >140/90 mmHg*. Other drugs should be added in order to achieve the desired BP.

ACE=Angiotensin converting enzyme, BP=Blood pressure, CKD=Chronic kidney disease, DM=Diabetes mellitus

*A BP >130/80 mmHg should be used for individuals with CKD or DM


I IIa IIb III

Blood Pressure RecommendationsBlood Pressure Recommendations

Secondary Prevention

Angiotensin Converting Angiotensin Converting Enzyme Inhibitor Evidence Enzyme Inhibitor Evidence

and Guidelinesand Guidelines

Evidence for Current Cardiovascular Evidence for Current Cardiovascular Disease Disease


Angiotensin II

Kininase II

Angiotensin I

Angiotensinogen

ACE

ReninBradykinin

Inactive Fragments

Sympathetic

VasopressinAldosterone

Vasoconstriction

ACE=Angiotensin converting enzyme

Kininogen

KallikreinVasodilatio

nProstaglandins

tPA

Inhibitor

ACE Inhibitor: ACE Inhibitor: Mechanism of ActionMechanism of Action

Days of Follow-Up

CV

death

, M

I,

or

stro

ke (

%)

22% RRR, P<0.0010.00

0.05

0.10

0.15

0.20

0 500 1000 1500

Placebo

Ramipril

Source: HOPE Investigators. NEJM 2000;342:145-153

Heart Outcomes Prevention and Evaluation (HOPE) Study

ACE=Angiotensin converting enzyme, DM=Diabetes mellitus, CV=Cardiovascular, HF=Heart failure, LVSD=Left

ventricular systolic dysfunction, MI=Myocardial infarction

9,297 patients with DM or vascular disease plus an additional CV risk factor, but without HF or known LVSD randomized to ramipril (10 mg) or placebo for 5 years

An ACE inhibitor provides benefit in high-risk individuals

ACE Inhibitor ACE Inhibitor Evidence: Secondary Evidence: Secondary PreventionPrevention

0 0.5 1 1.5 2

Cardiovascular death (0.86; 0.72-1.03)Non-fatal MI (0.78; 0.20-0.90)

Cardiac arrest (0.54; 0.20-1.47)

Combined endpoint (0.80; 0.71-0.91)

European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease

(EUROPA)

Favors Perindopril Favors Placebo

Source: EUROPA Investigators. Lancet 2003;362:782-788

12,218 patients with CAD and presumed normal LV function randomized to perindopril (8 mg) or placebo for 4 years

An ACE inhibitor provides benefit in intermediate-risk individuals

ACE=Angiotensin converting enzyme, CAD=Coronary artery disease, CV=Cardiovascular, MI=Myocardial infarction

ACE Inhibitor ACE Inhibitor Evidence: Evidence: Secondary Secondary PreventionPrevention

Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial

Pri

mary

End P

oin

t (%

)* 30

25

20

15

10

5

00 1 2 3 4 5 6

Years After Randomization

Placebo

Source: The PEACE Trial Investigators. NEJM 2004;351:2058-2068

*Includes death from cardiovascular causes, myocardial infarction, or coronary revascularization

Trandolapril

8,290 patients with stable CAD and normal LV function randomized to trandolapril (4 mg) or placebo for 5 years

An ACE inhibitor does not provide benefit in lower-risk individuals


ACE=Angiotensin converting enzyme, CAD=Coronary artery disease, LV=Left ventricular

Comparison between the HOPE and PEACE trials

Patients enrolled in the PEACE trial were lower risk*

MI, C

ard

iac

death

, or

Str

oke

(%

)

Source: The PEACE Trial Investigators. NEJM 2004;351:2058-2068

CHD=Coronary heart disease, MI=Myocardial infarction

*Reflects better blood pressure control, revascularization, and use of other risk-reducing medications (i.e., antiplatelet

therapy, beta-blocker, lipid-lowering medication)

Years

HOPE, placebo

HOPE, active drug (ramipril)

PEACE, placebo


Clinical Trial

HOPE 9,297 1051

0.4 0.6 0.8 1.0 1.2 1.4 1.6

N

ACE-I Better Placebo Better

EUROPA 12,218 795

PEACE 8,290 633 HR=0.89 P=0.13

HR=0.89 P=0.10

HR=0.84 P=0.005

Deaths

All Trials 33,960 >3000 HR=0.86 P<0.001

Sources:Danchin N et al. Arch Intern Med 2006;166:787-796

The HOPE Trial Investigators. NEJM 2000;342:145-153The EUROPA Study. Lancet 2003; 362: 782-788

The PEACE Trial Investigators. NEJM 2004;351:2058-2068

Meta-Analysis of the HOPE, EUROPA, and PEACE Trials*

RR of Mortality

*7 RCTs, 33,960 randomized patients, and 4.4 years of mean follow-up. Other findings include a CV mortality HR=0.81, MI HR=0.82, and stroke HR=0.77

ACE-I=Angiotensin converting enzyme inhihbitor, MI=Myocardial infarction


Years

Pro

babili

ty o

f Event

0

0.05

0.1

0.15

0.2

0.25

0.3

0 1 2 3

0.35

0.4

4

ACE-I

Placebo

OR 0.74 (0.66–0.83)OR 0.74 (0.66–0.83)

Source: Flather MD et al. Lancet 2000;355:1575–1581

SAVERadionucli

deEF <40%

AIREClinical and/or radiographic signs of HF

TRACEEchocardiogra

mEF <35%

ACE-I=Angiotensin converting enzyme inhibitor, EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio

An ACE-I provides substantial benefit in post-MI LVSD


An ACE inhibitor should be started and continued indefinitely in all patients with left ventricular ejection fraction <40% and in those with hypertension, DM, or CKD, unless contraindicated

An ACE inhibitor in all other patients

ACE=Angiotensin converting enzyme, CKD=Chronic kidney disease, DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction


I IIa IIb III

ACE Inhibitor RecommendationsACE Inhibitor Recommendations


I IIa IIb III


• Patients with a SBP >140 mm Hg or DBP >90 mm Hg should receive drug therapy in addition to lifestyle and behavioral therapy.

• All patients with hypertension should be treated with a regimen that includes an ACE inhibitor or an ARB. If one class is not tolerated, the other should be substituted. Other drug classes* that have been demonstrated to reduce CVD events should be added as needed to achieve BP targets.

• If ACE inhibitors, ARBs, or diuretics are used, renal function and serum potassium levels should be monitored within the first 3 months. If stable, follow-up could occur every 6 months.

ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, BP=Blood pressure, CV=Cardiovascular, CVD=Cardiovascular disease,

DBP=Diastolic blood pressure, DM=Diabetes mellitus, SBP=Systolic blood pressure

*Includes beta-blockers, thiazide diuretics, and calcium channel blockers


• If an ACE inhibitor, ARB, or diuretic is used, kidney function and serum potassium levels should be closely monitored.

• In pregnant patients with DM and chronic hypertension, BP target goals of 110-129/65-79 mm Hg are suggested in the interest of long-term maternal health and minimizing impaired fetal growth.

• An ACE inhibitor and ARB are contraindicated during pregnancy.


ACE=Angiotensin converting enzyme, ADA=American Diabetes Association, ARB=Angiotensin receptor blocker, BP=Blood pressure, DM=Diabetes mellitus


Angiotensin Receptor Blocker Angiotensin Receptor Blocker Evidence and GuidelinesEvidence and Guidelines



Receptors

AT II Receptor Blocker

Antiproliferative Action

Vasodilation

Proliferative Action

Vasoconstriction

ATIIATI

Angiotensinogen

Other Pathways

Renin

AT I Recepto

r Blocker

Angiotensin I

Angiotensin II

ACE

Angiotensin Receptor Angiotensin Receptor Blocker: Mechanism of Blocker: Mechanism of ActionAction

2,028 patients with symptomatic HF, LVSD (EF <40%), and intolerance to ACE inhibitor randomized to candesartan (32 mg)

or placebo for 34 months

An ARB provides benefit in those intolerant of an ACE inhibitor

0 1 2 3Years

50

HR 0.77 p=0.00040

40

30

20

10

Candesartan

Placebo

Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Alternative Trial

Source: Granger CB et al. Lancet 2003;362:772-777

ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, CV=Cardiovascular, EF=Ejection fraction,

HF=Heart failure, LVSD=Left ventricular systolic dysfunction

CV

Death

or

Hosp

italiz

ati

on

for

HF

Angiotensin Receptor Blocker Angiotensin Receptor Blocker Evidence: Secondary PreventionEvidence: Secondary Prevention

Source: Pfeffer M et al. NEJM 2003;349:1893-1906

Valsartan in Acute Myocardial Infarction Trial (VALIANT)

0.0

0.1

0.2

0.3

0.4

0 6 12 18 24 30 36

Valsartan

Valsartan and Captopril

Captopril

All

Cause

Mort

alit

y

Months

Valsartan vs. Captopril: HR = 1.00; P = 0.982

Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726

ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, EF=Ejection

fraction, LVSD=Left ventricular systolic dysfunction


14,703 patients with post-MI HF or LVSD (EF <0.40) randomized to captopril (50 mg tid), valsartan (160 mg bid), or captopril (50 mg tid)

plus valsartan (80 mg bid) for 2 years

An ARB provides similar efficacy to an ACE inhibitor in Post-MI LVSD

0 1 2 3

0

10

20

30

40

50

HR 0.85, p=0.011

Candesartan

Placebo

CV

Death

or

Hosp

italiz

ati

on

for

HF

Years

Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Added Trial

ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, EF=Ejection fraction, HF=Heart failure,

LVSD=Left ventricular systolic dysfunction

Source: McMurray JJ et al. Lancet 2003;362:767-771


2,548 patients with symptomatic HF and LVSD (EF <40%) randomized to candesartan (32 mg) or placebo in addition to an ACE

inhibitor for 34 months

Addition of an ARB to an ACE inhibitor may provide benefit in those with LVSD

Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET)

Source: ON TARGET Investigators. NEJM 2008;358:1547-1559

ACE-I=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, CVD=Cardiovascular disease, DM=Diabetes mellitus, MI=Myocardial infarction

CV Death / MI / Stroke / Hospitalization for Heart

Failure

CV Death / MI / Stroke / Hospitalization for Heart

Failure

0.8 0.9 1.0 1.1 1.2

RR (95% CI)

Non

-infe

riorit

y M

argi

n

Primary Composite (p = 0.003)

CV Death / MI / Stroke (HOPE Composite)

(p = <0.001)

Telmisartan better Ramipril better


25,620 patients with CVD or DM randomized to ramipril (10 mg), telmisartan (80 mg), or a combination of both for 56 months

An ARB provides similar efficacy to an ACE-I in high risk patients

Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET)

Source: ON TARGET Investigators. NEJM 2008;358-1547-1559

CVD=Cardiovascular disease, DM=Diabetes mellitus, MI=Myocardial infarction, RAS=Renin angiotensin system

CV

Death

, M

I,

Str

oke

, or

Hosp

italiz

ati

on f

or

Heart

Failu

re

0.20

0.15

0.10

0.05

0.000 1 2 3 4 5

Follow-up (years)

Telmisartan

Ramipril

Telmisartan plus ramipril*

*Dual RAS blockade leads to greater renal impairment HR=1.33

(p<0.001)

*Dual RAS blockade leads to greater renal impairment HR=1.33

(p<0.001)


25,620 patients with CVD or DM randomized to ramipril (10 mg), telmisartan (80 mg), or a combination of both for 56 months

Dual RAS blockade provides no additional benefit but leads to greater renal impairment

Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease

(TRANSCEND)

Perc

en

t of

pati

en

ts

P=0.216P=0.048

P=0.055

Source: TRANSCEND Investigators. Lancet. 2008;372:1174-83

*Primary endpoint is a composite of CV death, MI, stroke or heart failure hospitalization


*

ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, CV=Cardiovascular, MI=Myocardial infarction

5,926 high risk patients intolerant to ACE inhibitors randomized to telmisartan (80 mg) or placebo for 56

months

An ARB is well tolerated in those unable to take an ACE inhibitor

An ARB in patients who have HF or who have had a MI with left ventricular ejection fraction <40% and who are ACE-inhibitor intolerant

An ARB in other patients who are intolerant of an ACE inhibitor

Use of an ARB in combination with an ACE inhibitor is not well established in those with systolic heart failure

ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, HF=Heart failure, MI=Myocardial infarction


I IIa IIb III

Angiotensin Receptor Blocker Angiotensin Receptor Blocker RecommendationsRecommendationsSecondary Prevention

I IIa IIb III

I IIa IIb III


• Patients with a SBP >140 mm Hg or DBP >90 mm Hg should receive drug therapy in addition to lifestyle and behavioral therapy.

• All patients with hypertension should be treated with a regimen that includes an ACE inhibitor or an ARB. If one class is not tolerated, the other should be substituted. Other drug classes* that have been demonstrated to reduce CVD events should be added as needed to achieve BP targets.

• If ACE inhibitors, ARBs, or diuretics are used, renal function and serum potassium levels should be monitored within the first 3 months. If stable, follow-up could occur every 6 months.

ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, BP=Blood pressure, CV=Cardiovascular, CVD=Cardiovascular disease,

DBP=Diastolic blood pressure, DM=Diabetes mellitus, SBP=Systolic blood pressure

*Includes beta-blockers, thiazide diuretics, and calcium channel blockers


• If an ACE inhibitor, ARB, or diuretic is used, kidney function and serum potassium levels should be closely monitored.

• In pregnant patients with DM and chronic hypertension, BP target goals of 110-129/65-79 mm Hg are suggested in the interest of long-term maternal health and minimizing impaired fetal growth.

• An ACE inhibitor and ARB are contraindicated during pregnancy.


ACE=Angiotensin converting enzyme, ADA=American Diabetes Association, ARB=Angiotensin receptor blocker, BP=Blood pressure, DM=Diabetes mellitus


Beta-blockBeta-blocker Evidence and er Evidence and GuidelinesGuidelines

Evidence for Current Cardiovascular Evidence for Current Cardiovascular Disease Disease


Parasympathetic Nerve Terminal

Sympathetic Cholinergic Nerve Terminal

a1

M2

M2

M2

a1 b2

b2

b2

b1 a2

a2 a2

NE

ACh

Sympathetic Nerve Terminal

+++

_

NE NE_ +

_ _Heart Blood Vessel

Inotropy

Chronotropy

Dromotropy

Vasoconstriction

Vasoconstriction

Vasodilation

Vasodilation

1 selective blocker

non-selective blocker non-selective blocker with 1 blocking activity

a=Alpha receptor, Ach=Acetylcholine, b=Beta receptor, M=Muscarinic receptor, NE=Norepinephrine

Source: Klabunde, RE (ed) Cardiovascular Physiology Concepts LWW 2001

Beta-blocker:Beta-blocker:Targets and Receptor Targets and Receptor SelectivitySelectivity

Placebo-controlled post-MI trials* using oral beta-blockers

StudyPatients

(N)Treatment

GroupsDuration of Follow-Up

Effect on Mortality

Effect on Reinfarction

Göteborg Study† 1,395Metoprolol

tartrate3 months

36%(P.03)

PNS

Timolol Trial(Norwegian)

1,884 Timolol 17 months 39%

(P.003) 28%

(P.0005)

Lopressor Intervention

Trial2,395

Metoprolol tartrate

12 months PNS NA

Beta-blocker Heart Attack Trial

3,837 Propranolol 25 months 26%

(P.005)PNS

CAPRICORN Trial 1,959 Carvedilol 15 months 23%

(P=.03) 40%

(P.01)

*Includes the largest trials performed to date†Patients received IV followed by oral metoprolol

MI=Myocardial infarction, NA=Not applicable, NS=Not significant

Beta-blocker Evidence:Beta-blocker Evidence:Secondary PreventionSecondary Prevention

Phase of Treatment

Acute treatment

Secondaryprevention

Overall

Total #Patients

28,970

24,298

53,268

0.5 1.0 2.0RR of death

Beta-blockerbetter

RR (95% CI)

Placebobetter

0.87 (0.77-0.98)

0.77 (0.70-0.84)

0.81 (0.75-0.87)

Source: Antman E, Braunwald E. Acute Myocardial Infarction. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A textbook of Cardiovascular

Medicine, 6th ed., Philadelphia, PA: W.B. Sanders, 2001, 1168.

Summary of secondary prevention trials of beta-blocker therapy

CI=Confidence interval, RR=Relative risk

Beta-blocker Evidence:Beta-blocker Evidence:Secondary PreventionSecondary Prevention

*Not an approved indication, †Not a planned end point

#Not approved for severe HF/mortality reduction alone

HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NS=Not significant, TX=Transplant

Study Drug HF Severity

Patients (n)

Follow-up

Mean Dosage

Effects on Outcomes

CIBIS Bisoprolol* Moderate-Severe

641 1.9 Years 3.8 mg/day

All cause mortality (p=NS)

CIBIS-II Bisoprolol* Moderate-Severe

2,647 1.3 Years 7.5mg/day

All cause mortality34% (P<0.0001)

BEST Bucindolol* Moderate-Severe

2,708 2.0 Years 152mg/day

All cause mortality (p=NS)

MERIT-HF Metoprolol succinate#

Mild-Moderate


All cause mortality34% (P=0.0062)

MDC Metoprolol tartrate*

Mild-Moderate

383 1.0 Years 108mg/day

Death or Need for TX (P=NS)

CAPRICORN Carvedilol Mild 1,989 1.3 Years 40mg/day

All cause mortality 23% (P =0.03)

US Carvedilol

Carvedilol Mild-Moderate


All-cause mortality†65% (P=.0001)

COPERNICUS Carvedilol Severe 2,289 0.9 Years 37mg/day

All-cause mortality35% (P =0.0014)

SENIORS Nebivolol Moderate 2,128 3.0 Years 7.7 mg/day

All-cause mortality or CV hospitalization

14% (P =0.039)

Beta-blocker Evidence:Beta-blocker Evidence:Benefit in HF and/or LVSDBenefit in HF and/or LVSD

Beta-blocker should be used in all patients with LVSD (ejection fraction <40%) with HF or prior MI, unless contraindicated*. (Use should be limited to carvedilol, metoprolol succinate, or bisoprolol, which have been shown to reduce mortality.)

Beta-blocker for 3 years in all patients with normal left ventricular function who have had a MI or ACS

Beta-blocker beyond 3 years as chronic therapy in all patients with normal left ventricular function who have had a MI or ACS

*Relative contraindications include asthma, chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe

peripheral arterial disease, and a PR interval >0.24 seconds

ACS=Acute coronary syndrome, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction


I IIa IIb III

Beta-Blocker RecommendationsBeta-Blocker Recommendations


I IIa IIb III

I IIa IIb III

Beta-blocker in patients with LVSD (ejection fraction <40%) without HF or prior MI

Beta-blocker as chronic therapy for all other patients with coronary or other vascular disease

HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction


Beta-Blocker Recommendations Beta-Blocker Recommendations (Continued)(Continued) Secondary Prevention

I IIa IIb III

I IIa IIb III

3 acc prevention blood pressure

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