Transcript Slide 1

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 Recommendations
and Levels of 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.
Icons Representing the Classification and Evidence
Levels for Recommendations
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
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Blood Pressure Evidence
High Blood Pressure*:
Prevalence Increases with Age
Hypertension* Prevalence (%)
National Health and Nutrition Examination Survey (NHANES) III
66%
72%
51%
38%
18%
3%
18-29
9%
30-39
40-49
50-59
60-69
70-79
80+
Age
The prevalence of high blood pressure increases with age
*Hypertension defined as blood pressure >140/90 mmHg or treatment
Source: JNC-VI. Arch Intern Med 1997;157:2413-2446
High Blood Pressure*:
Prevalence in Different Patient Groups
National Health and Nutrition Examination Survey (NHANES)
*High blood pressure defined as blood pressure 140/90 mmHg or treatment
Source: Yoon SS et al. NCHS Data Brief 2012;107:1-7
High Blood Pressure:
Lifetime Risk*
Risk of hypertension (%)
Framingham Heart Study
Men
Women
Years
*Residual lifetime risk of developing hypertension among people
with blood pressure <140/90 mmHg starting at age 55-65 years
Source: Vasan RS et al. JAMA 2002; 287:1003-1010
Change in Blood Pressure Levels in
the United States Over Time
Blood pressure
age-adjusted percentage
National Health and Nutrition Examination Survey (NHANES)
Source: Ford ES et al. Figure 2b, Circulation 2009;120:1181-1188
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Blood Pressure Treatment
Evidence and Guidelines
JNC VII Guidelines:
Measurement of Blood Pressure
Method
In-office
Brief Description
Two readings, 5 minutes apart, sitting in chair
Confirm elevated reading in contralateral arm
Ambulatory BP
monitoring
Indicated for evaluation of “white-coat” HTN.
Absence of 10–20% BP decrease during sleep
indicates increased CVD risk
Self-measurement
Provides information on response to treatment.
May help improve adherence to treatment and
evaluate “white-coat” HTN
BP=Blood pressure, CVD=Cardiovascular
disease, HTN=Hypertension
Source: Chobanian AV et al. JAMA 2003;289:2560-2572
JNC VII Guidelines:
Causes of Secondary Hypertension
Medical Conditions
Drugs
Chronic kidney disease
NSAIDs
Primary hyperaldosteronism
Oral contraceptives
Renovascular disease
Adrenal steroids
Chronic steroid therapy
Sympathomimetics
Cushing’s syndrome
Cyclosporine or tacrolimus
Pheochromocytoma
Erythropoietin
Aortic coarctation
Ephedra, mu huang, bitter orange
Thyroid or parathyroid disease
Cocaine or amphetamines
Sleep apnea
Alcohol
NSAIDs=Non-steroidal anti-inflammatory drugs
Source: Chobanian AV et al. JAMA 2003;289:2560-2572
Resistant Hypertension
Diagnostic and Treatment Algorithm
Confirm Treatment Resistance
Office BP >140/90 or 130/80 mm Hg in patients with DM
or chronic kidney disease
and
Patient prescribed 3 or more antihypertensive
medications at optimal doses, including if possible a
diuretic
or
Office BP at goal but patient requiring 4 or more
antihypertensive medications
Exclude Pseudoresistance
Identify/Reverse Contributing Lifestyle Factors
Obesity
Physical inactivity
Excessive alcohol ingestion
High salt, low fiber diet
Discontinue/Minimize Interfering Substances
Non-steroidal anti-inflammatory agents
Sympathomimetics (diet pills, decongestants)
Stimulants
Oral contraceptives
Licorice
Ephedra
Is patient adherent with prescribed reigmen?
Obtain home, work, or ambulatory BP readings to exclude
white coat effect
BP=Blood pressure, DM=Diabetes mellitus
Source: Calhoun DA et al. Circulation 2008;117:e510-526
Resistant Hypertension (Continued)
Diagnostic and Treatment Algorithm
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 Treatment
Maximize diuretic therapy, including possible addition of
mineralocorticoid receptor antagonist
Combine agents with different mechanisms of action
Use loop diuretics in patients with chronic kidney
disease and/or those receiving potent vasodilators (e.g.,
minoxidil)
Refer 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
CrCl=Creatinine clearance
Source: Calhoun DA et al. Circulation 2008;117:e510-526
High Blood Pressure Evidence:
Increased Risk with Increased Levels
256
Age at Risk (Y)
80-89
128
70-79
64
60-69
32
50-59
16
40-49
8
4
2
1
0
120 140 160 180
Usual Systolic BP (mm Hg)
256
Ischemic Heart Disease Mortality
(Floating absolute risk)
Ischemic Heart Disease Mortality
(Floating absolute risk)
Ischemic heart disease mortality and blood pressure
Age at Risk (Y)
80-89
128
70-79
64
60-69
32
50-59
16
40-49
8
4
2
1
0
70 80 90 100 110
Usual Diastolic BP (mm Hg)
BP=Blood pressure
Source: Prospective Studies Collaboration. Lancet 2002;360:1903-1913
High Blood Pressure Evidence:
Risk of CHD with Treatment
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
0.79
(0.69 to 0.90)
Total
0
2.0
0.5
1.5
1.0
Better than placebo
Worse than placebo
CHD=Coronary heart disease
Source: He J et al. Am Heart J 1999;138:211-219
High Blood Pressure Evidence:
Number of Medications Needed
Trial (SBP Achieved)
UKPDS (144 mm Hg)
ABCD (127 mm Hg)
MDRD (132 mm Hg)
HOT (138 mm Hg)
AASK (127 mm Hg)
1
1.5
2
2.5
3
3.5
4
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
Source: Abbott K et al. J Clin Pharmacology 2004;44:431-438
Blood Pressure Lowering Therapy Evidence:
Primary Prevention
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
Attack Trial (ALLHAT)
33,357 patients with HTN and >1 CHD risk factor randomized to
chlorthalidone, amlodipine, or lisinopril for 5 years
Rate of MI or
fatal CHD
.20
Chlorthalidone
Amlodipine
Lisinopril
.16
.12
.08
RR
.04
0
0
1
2
(95% CI)
P-value
A/C 0.98
(0.90-1.07)
0.65
L/C
(0.91-1.08)
0.81
3
4
Years to CHD Event
0.99
5
6
7
All three BP lowering agents provide similar efficacy
BP=Blood pressure, CHD=Coronary heart disease,
HTN=Hypertension, MI=Myocardial infarction
Source: ALLHAT Investigators. JAMA 2002;288:2981-2997
Blood Pressure Lowering Therapy Evidence:
Primary Prevention
Losartan Intervention for Endpoint (LIFE) Reduction in
Hypertension Study
Proportion with CV
death, MI, or stroke (%)
9,193 high-risk hypertensive* patients with LVH randomized to losartan
(100 mg) or atenolol (100 mg) for 5 years
16
12
Atenolol
Losartan
8
4
13% RRR, P=0.021
0
0
6
12
18
24
30
36
42
48
54
60
66
Study Month
An ARB provides greater efficacy in patients with LVH
*Defined by SBP=160-200 mmHg or DBP=95-115 mmHg
ARB=Angiotensin receptor blocker, CV=Cardiovascular,
DBP=Diastolic blood pressure, LVH=Left ventricular hypertrophy,
MI=Myocardial infarction, SBP=Systolic blood pressure
Source: Dahlöf B et al. Lancet 2002;359:995-1003
Blood Pressure Lowering Therapy Evidence:
Primary Prevention
Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure
Lowering Arm (ASCOT-BPLA)
Nonfatal MI and
fatal CHD (%)
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
6
Atenolol-based regimen
4
Amlodipine-based regimen
2
RRR=10%, P=0.1052
0
0
1
2
3
4
5
Time since randomization (years)
6
Both BP lowering regimens provide similar efficacy
BP=Blood pressure, CV=Cardiovascular,
CHD=Coronary heart disease, MI=Myocardial infarction
Source: Dahlöf B et al. Lancet 2005;366:895-906
Blood Pressure Lowering Therapy Evidence:
Primary Prevention
Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure
Lowering Arm (ASCOT-BPLA)
Secondary endpoints
Nonfatal MI + fatal CHD
Total coronary endpoint
Total CV events/procedures
All-cause mortality
CV mortality
Fatal/nonfatal stroke
Fatal/nonfatal HF
Amlodipinebased
rate/1000
patient years
7.4
14.6
27.4
13.9
4.9
6.2
2.5
Atenolol-based
rate/1000
patient years
Amlodipinebased
better
Atenololbased
better
8.5
16.8
32.8
15.5
6.5
8.1
3.0
P
<0.05
<0.01
<0.0001
<0.05
0.001
<0.001
NS
0.50
0.70 1.00
1.45
2.00
An amlodopine-based regimen appears to reduce the rate of other CV events
CHD=Coronary heart disease, CV=Cardiovascular,
HF=Heart failure, MI=Myocardial infarction
Source: Dahlöf B et al. Lancet 2005;366:895-906
Blood Pressure Lowering Therapy Evidence:
Primary Prevention
Avoiding Cardiovascular Events Through Combination Therapy in
Patients Living with Systolic Hypertension (ACCOMPLISH)
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*
Composite of CV death,
MI, stroke, hospitalization
for angina, sudden cardiac
arrest, and coronary
revascularization (%)
0.16
0.14
0.12
Benazepril/HCTZ
0.10
0.08
Benazepril/Amlodipine
0.06
0.04
0.02
20% RRR, HR=0.80, P=0.0002
0.00
0
200
400
600
800
1000
1200
1400
An amlodipine-based regimen provides greater benefit
*The study was prematurely stopped
CV=Cardiovascular, MI=Myocardial infarction
Source: Jamerson K et al. NEJM 2008;359:2417-2428
Blood Pressure Lowering Therapy Evidence:
Primary Prevention
Hypertension in the Very Elderly (HYVET) Trial
Rate/1000 patient years (%)
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
P=0.02
P<0.001
Indapamide +
perindopril
Placebo
P=0.06
P=0.05
P<0.001
(Primary end point)
Blood pressure control in patients >80 years of age provides benefit
CV=Cardiovascular, CVA=Cerebrovascular accident
Source: Beckett NS et al. NEJM 2008;358:1887-1898
Blood Pressure Lowering Therapy Evidence:
Secondary Prevention
International Verapamil-Trandolapril Study (INVEST)
Incidence of all cause
death, nonfatal MI, or
nonfatal stroke
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
Calcium antagonist strategy (CAS)*
Non-calcium antagonist strategy (NCAS)*
20
15
10
5
RR=0.98, P=0.57
0
0
6
12
18
24
30
36
42
48
54
60
Months
Both a CAS and NCAS provide similar efficacy
*Trandolapril (up to 4 mg) was added in those with diabetes
mellitus, chronic kidney disease, or heart failure
BP=Blood pressure, CAS=Calcium antagonist strategy, HTN=Hypertension,
MI=Myocardial infarction, NCAS=Non-calcium antagonist strategy
Source: Pepine CJ et al. JAMA 2003;290:2805-2816
Blood Pressure Lowering Therapy Evidence:
Secondary Prevention
Valsartan Antihypertensive Long-Term Use
Evaluation (VALUE) Trial
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
Primary cardiac composite endpoint
Cardiac mortality
Cardiac morbidity
All myocardial infarction
All congestive heart failure
All stroke
All-cause death
New-onset diabetes
0.5
1
2
Favors valsartan
Favors amlodipine
Both blood pressure lowering regimens provide similar efficacy
BP=Blood pressure, CV=Cardiovascular, HTN=Hypertension
Source: Julius S et al. Lancet 2004;363:2022-2031
Blood Pressure Lowering Therapy Evidence:
Secondary Prevention
Comparison of Amlodipine vs Enalapril to Limit Occurrences of
Thrombosis (CAMELOT) Trial
CV event rate*
1,991 patients with CAD and a DBP <100 mmHg randomized to amlodipine
(10 mg), enalapril (20 mg), or placebo for 2 years
0.25
130/78
124/77
125/77
Placebo
Enalapril
Amlodipine
0.20
0.15
Follow-up BP
(mmHg)
0.10
0.05
0
0
6
12
18
24
Months
Treatment with amlodipine results in reduced CV events
*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
BP=Blood pressure, CAD=Coronary artery disease,
CV=Cardiovascular, DBP=Diastolic blood pressure
Source: Nissen S et al. JAMA 2004;292:2217-2226
Blood Pressure Lowering Therapy Evidence:
Effect of Intensive Blood Pressure Control
Hypertension Optimal Treatment (HOT) Study
Major CV events per
1000 patient-years
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
Patients with
Diabetes
Patients without
Diabetes
Diastolic BP goal
Diastolic BP goal
More intensive blood pressure control provides greater benefit in diabetics
BP=Blood pressure, CV=Cardiovascular
Source: Hansson L et al. Lancet 1998;351:1755-1762
Blood Pressure Lowering Therapy Evidence:
Effect of Intensive Blood Pressure Control
Cardio-SIS Trial
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)
21
14
11.4
7
0
Usual Control
P=0.003
15
17.0
Composite of CV
events* (%)
Incidence of LVH (%)
P=0.013
Tight Control
10
9.4
4.8
5
0
Usual Control
Tight Control
More intensive blood pressure control provides greater benefit
*Composite of death, MI, CVA, TIA, CHF, angina, new AF,
revascularization, aortic dissection, PAD, and ESRD
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
Source: Verdecchia P et al. Lancet 2009;374:525-533
Blood Pressure Lowering Therapy Evidence:
Effect of Intensive Blood Pressure Control
International Verapamil-Trandolapril Study (INVEST)—DM
Substudy
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
HR=1.15, p=0.036
Tight BP control is not associated with reduced adverse CV events
BP=Blood pressure, CV=Cardiovascular
Source: Cooper-DeHoff RM et al. JAMA 2010;304:61-68
Blood Pressure Lowering Therapy Evidence:
Effect of Intensive Blood Pressure Control
Action to Control Cardiovascular Risk in Diabetes (ACCORD)
Blood Pressure Trial
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
HR=0.88
95% CI (0.73-1.06)
HR=0.59
95% CI (0.39-0.89)
15
10
5
0
Patients with Events (%)
20
Total stroke
Patients with Events (%)
Nonfatal MI, nonfatal
stroke, or CV death
20
15
10
5
0
0
1
2
3
4
5
6
7
Years Post-Randomization
8
0
1
2
3
4
5
6
7
8
Years Post-Randomization
Intensive BP control in DM does not reduce a composite of adverse CV
events, but does reduce the rate of stroke
BP=Blood pressure, DM=Diabetes mellitus,
HR=Hazard ratio, SBP=Systolic blood pressure
ACCORD study group. NEJM 2010;362:1575-1585
JNC VII Guidelines:
Management and Treatment
Initial drug therapy
BP
classification
SBP*
mmHg
DBP*
mmHg
Lifestyle
modification
Without compelling
indications
With compelling
indications
<120 and <80
Encourage
Prehypertension
120–139 or 80–89
Yes
No antihypertensive drug
indicated.
Drug(s) for compelling
indications.‡
Stage 1
Hypertension
140–159 or 90–99
Yes
Thiazide-type diuretics for
most. May consider ACE-I,
ARB, BB, CCB, or combination
of these.
2-drug combination for most†
(usually thiazide-type diuretic
and ACE-I or ARB or BB or
CCB).
Drug(s) for compelling
indications.‡
Other antihypertensive
drugs (as needed).
Normal
Stage 2
Hypertension
>160 or >100
Yes
*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
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
Source: Chobanian AV et al. JAMA 2003;289:2560-2572
JNC VII Guidelines:
Lifestyle Modifications for BP Control
Modification
Recommendation
Approximate SBP
Reduction Range
Weight reduction
Maintain normal body weight (BMI=18.525)
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
Source: Chobanian AV et al. JAMA 2003;289:2560-2572
JNC VII Guidelines:
Compelling Indications for Drug Classes
Compelling Indication
Initial Therapy Options
Clinical-Trial Basis
Heart Failure
Diuretic, BB, ACE-I,
ARB, Aldo ANT
MERIT-HF, COPERNICUS, CIBIS,
SOLVD, AIRE, TRACE, Val-HeFT,
RALES
Post-MI
BB, ACE-I, Aldo ANT
ACC/AHA Post-MI Guidelines, BHAT,
SAVE, Capricorn, EPHESUS
High CAD Risk
Diuretic, BB, ACE-I, CCB
ALLHAT, HOPE, ANBP2,
LIFE, CONVINCE
Diabetes Mellitus
Diuretic, BB, ACE-I,
ARB, CCB
NKF-ADA Guideline,
UKPDS, ALLHAT
Chronic Kidney Disease
ACE-I, ARB
NKF Guidelines, Captopril Trial,
RENAAL, IDNT, REIN, AASK
Recurrent Stroke Prevention
Diuretic, ACE-I
PROGRESS
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
Source: Chobanian AV et al. JAMA 2003;289:2560-2572
JNC VII Guidelines:
Blood Pressure Treatment Algorithm
Lifestyle modifications
Not at goal BP (<140/90 mm Hg)
(<130/80 mm Hg for those with diabetes mellitus
or chronic kidney disease)
Initial drug choices
WITHOUT 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.
WITH compelling indications
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.
Not at goal BP
Optimize dosages or add additional drugs until goal BP is achieved.
Consider consultation with hypertension specialist.
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
Source: Chobanian AV et al. JAMA 2003;289:2560-2572
Blood Pressure Recommendations
Primary and Secondary Prevention
I IIa IIb III
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
AHA Primary Prevention of CV Disease in DM
Blood Pressure Recommendations
Primary Prevention
• 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
Source: Buse JB et al. Circulation 2007;115:114-126
AHA Primary Prevention of CV Disease in DM
Blood Pressure Recommendations (Continued)
Primary 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
Source: Buse JB et al. Circulation 2007;115:114-126
ADA Blood Pressure Recommendations
for Patients with Diabetes Mellitus
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.
ADA=American Diabetes Association, BP=Blood pressure, DBP=Diastolic
blood pressure, DM=Diabetes mellitus, SBP=Systolic blood pressure
Source: American Diabetes Association. Diabetes Care 2010;33:S11-61
ADA Blood Pressure Recommendations
for Patients with Diabetes Mellitus (Continued)
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
Source: American Diabetes Association. Diabetes Care 2010;33:S11-61
ADA Blood Pressure Recommendations
for Patients with Diabetes Mellitus (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
Source: American Diabetes Association. Diabetes Care 2010;33:S11-61
Blood Pressure Recommendations
Secondary Prevention
I IIa IIb III
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.
*A BP >130/80 mmHg should be used for individuals with CKD or DM
ACE=Angiotensin converting enzyme, BP=Blood pressure,
CKD=Chronic kidney disease, DM=Diabetes mellitus
Source: Smith SC Jr. et al. JACC 2011;58:2432-2446
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Angiotensin Converting
Enzyme Inhibitor Evidence
and Guidelines
ACE Inhibitor:
Mechanism of Action
Angiotensin II
ACE
Inactive Fragments
Inhibitor
Angiotensin I
Bradykinin
Renin
Angiotensinogen
Sympathetic
Vasopressin
Aldosterone
Vasoconstriction
Kininase II
Kininogen
Kallikrein
tPA
Vasodilation
Prostaglandins
ACE=Angiotensin converting enzyme
ACE Inhibitor Evidence:
Secondary Prevention
Heart Outcomes Prevention and Evaluation (HOPE) Study
CV death, MI, or
stroke (%)
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
0.20
Placebo
0.15
Ramipril
0.10
0.05
22% RRR, P<0.001
0.00
0
500
1000
1500
Days of Follow-Up
An ACE inhibitor provides benefit in high-risk individuals
ACE=Angiotensin converting enzyme, DM=Diabetes
mellitus, CV=Cardiovascular, HF=Heart failure, LVSD=Left
ventricular systolic dysfunction, MI=Myocardial infarction
Source: HOPE Investigators. NEJM 2000;342:145-153
ACE Inhibitor Evidence:
Secondary Prevention
European Trial on Reduction of Cardiac Events with Perindopril
in Stable Coronary Artery Disease (EUROPA)
12,218 patients with CAD and presumed normal LV function
randomized to perindopril (8 mg) or placebo for 4 years
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)
0
0.5
Favors Perindopril
1
2
1.5
Favors Placebo
An ACE inhibitor provides benefit in intermediate-risk individuals
ACE=Angiotensin converting enzyme, CAD=Coronary artery
disease, CV=Cardiovascular, MI=Myocardial infarction
Source: EUROPA Investigators. Lancet 2003;362:782-788
ACE Inhibitor Evidence:
Secondary Prevention
Prevention of Events with Angiotensin Converting Enzyme
Inhibition (PEACE) Trial
8,290 patients with stable CAD and normal LV function randomized to
trandolapril (4 mg) or placebo for 5 years
Primary End Point (%)*
30
Placebo
Trandolapril
25
20
15
10
5
0
0
1
2
3
4
5
6
Years After Randomization
An ACE inhibitor does not provide benefit in lower-risk individuals
*Includes death from cardiovascular causes,
myocardial infarction, or coronary revascularization
ACE=Angiotensin converting enzyme, CAD=Coronary artery disease, LV=Left ventricular
Source: The PEACE Trial Investigators. NEJM 2004;351:2058-2068
ACE Inhibitor Evidence:
Secondary Prevention
Comparison between the HOPE and PEACE trials
MI, Cardiac death,
or Stroke (%)
HOPE, placebo
HOPE, active drug
(ramipril)
PEACE, placebo
Years
Patients enrolled in the PEACE trial were lower risk*
*Reflects better blood pressure control, revascularization,
and use of other risk-reducing medications (i.e., antiplatelet
therapy, beta-blocker, lipid-lowering medication)
CHD=Coronary heart disease, MI=Myocardial infarction
Source: The PEACE Trial Investigators. NEJM 2004;351:2058-2068
ACE Inhibitor Evidence:
Secondary Prevention
Meta-Analysis of the HOPE, EUROPA, and PEACE Trials*
Clinical Trial
N
HOPE
9,297
Deaths
RR of Mortality
1051
HR=0.84 P=0.005
EUROPA
12,218
795
HR=0.89 P=0.10
PEACE
8,290
633
HR=0.89 P=0.13
33,960
>3000
HR=0.86 P<0.001
All Trials
0.4
0.6
0.8
ACE-I Better
1.0
1.2
1.4
1.6
Placebo Better
*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
Sources:
Danchin N et al. Arch Intern Med 2006;166:787-796
The HOPE Trial Investigators. NEJM 2000;342:145-153
The EUROPA Study. Lancet 2003; 362: 782-788
The PEACE Trial Investigators. NEJM 2004;351:2058-2068
Probability of Event
ACE Inhibitor Evidence:
Secondary Prevention
SAVE
AIRE
Radionuclide
EF <40%
Clinical and/or
radiographic
signs of HF
TRACE
Echocardiogram
EF <35%
0.4
0.35
Placebo
0.3
ACE-I
0.25
0.2
0.15
0.1
OR 0.74 (0.66–0.83)
0.05
0
0
1
2
3
4
Years
An ACE-I provides substantial benefit in post-MI LVSD
ACE-I=Angiotensin converting enzyme inhibitor, EF=Ejection fraction, LVSD=Left
ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio
Source: Flather MD et al. Lancet 2000;355:1575–1581
ACE Inhibitor Recommendations
Secondary Prevention
I IIa IIb III
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
I IIa IIb III
An ACE inhibitor in all other patients
ACE=Angiotensin converting enzyme, CKD=Chronic kidney disease,
DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction
Source: Smith SC Jr. et al. JACC 2011;58:2432-2446
AHA Primary Prevention of CV Disease in DM
Blood Pressure Recommendations
Primary Prevention
• 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.
*Includes beta-blockers, thiazide diuretics, and calcium channel blockers
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
Source: Buse JB et al. Circulation 2007;115:114-126
ADA Blood Pressure Recommendations
for Patients with Diabetes Mellitus (Continued)
Primary Prevention
• 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
Source: American Diabetes Association. Diabetes Care 2010;33:S11-61
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Angiotensin Receptor Blocker
Evidence and Guidelines
Angiotensin Receptor Blocker:
Mechanism of Action
Renin
Angiotensinogen
Other Pathways
AT I
Receptor
Blocker
ATI
Angiotensin I
Angiotensin II
Receptors
ACE
AT II
Receptor
Blocker
ATII
Vasoconstriction Proliferative Vasodilation
Action
Antiproliferative
Action
Angiotensin Receptor Blocker Evidence:
Secondary Prevention
Candesartan in Heart Failure Assessment of Reduction in Mortality
and Morbidity (CHARM) Alternative Trial
2,028 patients with symptomatic HF, LVSD (EF <40%), and intolerance to
ACE inhibitor randomized to candesartan (32 mg) or placebo for 34 months
CV Death or
Hospitalization
for HF
50
Placebo
40
30
Candesartan
20
10
HR 0.77 p=0.0004
0
0
1
2
Years
3
An ARB provides benefit in those intolerant of an ACE inhibitor
ACE=Angiotensin converting enzyme, ARB=Angiotensin
receptor blocker, CV=Cardiovascular, EF=Ejection fraction,
HF=Heart failure, LVSD=Left ventricular systolic dysfunction
Source: Granger CB et al. Lancet 2003;362:772-777
Angiotensin Receptor Blocker Evidence:
Secondary Prevention
Valsartan in Acute Myocardial Infarction Trial (VALIANT)
All Cause Mortality
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
0.4
Captopril
0.3
Valsartan
Valsartan and Captopril
0.2
0.1
Valsartan vs. Captopril: HR = 1.00; P = 0.982
Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726
0.0
0
6
12
18
24
30
36
Months
An ARB provides similar efficacy to an ACE inhibitor in Post-MI LVSD
ACE=Angiotensin converting enzyme,
ARB=Angiotensin receptor blocker, EF=Ejection
fraction, LVSD=Left ventricular systolic dysfunction
Source: Pfeffer M et al. NEJM 2003;349:1893-1906
Angiotensin Receptor Blocker Evidence:
Secondary Prevention
Candesartan in Heart Failure Assessment of Reduction in Mortality
and Morbidity (CHARM) Added Trial
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
CV Death or
Hospitalization
for HF
50
40
Placebo
30
Candesartan
20
10
HR 0.85, p=0.011
0
0
1
2
Years
3
Addition of an ARB to an ACE inhibitor may provide benefit in those with LVSD
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
Angiotensin Receptor Blocker Evidence:
Secondary Prevention
Ongoing Telmisartan Alone and in Combination with Ramipril
Global Endpoint Trial (ONTARGET)
Non-inferiority Margin
25,620 patients with CVD or DM randomized to ramipril (10 mg),
telmisartan (80 mg), or a combination of both for 56 months
Primary Composite
(p = 0.003)
CV Death / MI / Stroke /
Hospitalization for Heart Failure
CV Death / MI / Stroke
(HOPE Composite)
(p = <0.001)
Telmisartan better
0.8
Ramipril better
0.9
1.0
1.1
1.2
RR (95% CI)
An ARB provides similar efficacy to an ACE-I in high risk patients
ACE-I=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker,
CVD=Cardiovascular disease, DM=Diabetes mellitus, MI=Myocardial infarction
Source: ON TARGET Investigators. NEJM 2008;358:1547-1559
Angiotensin Receptor Blocker Evidence:
Secondary Prevention
Ongoing Telmisartan Alone and in Combination with Ramipril
Global Endpoint Trial (ONTARGET)
25,620 patients with CVD or DM randomized to ramipril (10 mg),
telmisartan (80 mg), or a combination of both for 56 months
CV Death, MI, Stroke,
or Hospitalization for
Heart Failure
0.20
Telmisartan plus ramipril*
Telmisartan
0.15
Ramipril
0.10
*Dual RAS blockade leads
to greater renal impairment
HR=1.33 (p<0.001)
0.05
0.00
0
1
2
3
Follow-up (years)
4
5
Dual RAS blockade provides no additional benefit but leads to greater
renal impairment
CVD=Cardiovascular disease, DM=Diabetes mellitus,
MI=Myocardial infarction, RAS=Renin angiotensin system
Source: ON TARGET Investigators. NEJM 2008;358-1547-1559
Angiotensin Receptor Blocker Evidence:
Secondary Prevention
Telmisartan Randomized Assessment Study in ACE Intolerant
Subjects with Cardiovascular Disease (TRANSCEND)
5,926 high risk patients intolerant to ACE inhibitors randomized to
telmisartan (80 mg) or placebo for 56 months
Percent of patients
P=0.055
P=0.216
P=0.048
*
An ARB is well tolerated in those unable to take an ACE inhibitor
*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
Source: TRANSCEND Investigators. Lancet. 2008;372:1174-83
Angiotensin Receptor Blocker Recommendations
Secondary Prevention
I IIa IIb III
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
I IIa IIb III
An ARB in other patients who are intolerant of an ACE
inhibitor
I IIa IIb III
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
Source: Smith SC Jr. et al. JACC 2011;58:2432-2446
AHA Primary Prevention of CV Disease in DM
Blood Pressure Recommendations
Primary Prevention
• 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.
*Includes beta-blockers, thiazide diuretics, and calcium channel blockers
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
Source: Buse JB et al. Circulation 2007;115:114-126
ADA Blood Pressure Recommendations
for Patients with Diabetes Mellitus (Continued)
Primary Prevention
• 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
Source: American Diabetes Association. Diabetes Care 2010;33:S11-61
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Beta-blocker Evidence and
Guidelines
Beta-blocker:
Targets and Receptor Selectivity
Heart
Inotropy
Chronotropy
Dromotropy
+
+
+
_
a2
b1
b2
a1
M2
b1 selective blocker
b non-selective blocker
b non-selective blocker
with a1 blocking
activity
Parasympathetic
Nerve Terminal
NE
_
_
Blood Vessel
a2
_
NE
NE
+
M2
b2
a2
Vasoconstriction
a1
Vasoconstriction
b2
Vasodilation
M2 Vasodilation
Sympathetic
Nerve Terminal
ACh
Sympathetic Cholinergic Nerve
Terminal
a=Alpha receptor, Ach=Acetylcholine, b=Beta receptor,
M=Muscarinic receptor, NE=Norepinephrine
Source: Klabunde, RE (ed) Cardiovascular Physiology Concepts LWW 2001
Beta-blocker Evidence:
Secondary Prevention
Placebo-controlled post-MI trials* using oral beta-blockers
Study
Patient
s
(N)
Göteborg Study†
1,395
Metoprolol
tartrate
3 months
 36%
(P.03)
PNS
Timolol Trial
(Norwegian)
1,884
Timolol
17 months
 39%
(P.003)
 28%
(P.0005)
Lopressor
Intervention
Trial
2,395
Metoprolol
tartrate
12 months
PNS
NA
Beta-blocker Heart
Attack Trial
3,837
Propranolol
25 months
 26%
(P.005)
PNS
CAPRICORN Trial
1,959
Carvedilol
15 months
 23%
(P=.03)
 40%
(P.01)
Treatment
Groups
Duration of
Follow-Up
Effect on
Mortality
Effect on
Reinfarction
*Includes the largest trials performed to date
received IV followed by oral metoprolol
†Patients
MI=Myocardial infarction, NA=Not applicable, NS=Not significant
Beta-blocker Evidence:
Secondary Prevention
Summary of secondary prevention trials of beta-blocker therapy
Phase of
Treatment
Total #
Patients
RR (95% CI)
Acute
treatment
28,970
0.87 (0.77-0.98)
Secondary
prevention
24,298
0.77 (0.70-0.84)
Overall
53,268
0.81 (0.75-0.87)
0.5
1.0
RR of death
Beta-blocker
Placebo
better
better
2.0
CI=Confidence interval, RR=Relative risk
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.
Beta-blocker Evidence:
Benefit in HF and/or LVSD
Study
Drug
HF
Severity
Patients
(n)
Follow-up
Mean Dosage
Effects on
Outcomes
CIBIS
Bisoprolol*
ModerateSevere
641
1.9 Years
3.8
mg/day
All cause mortality
(p=NS)
CIBIS-II
Bisoprolol*
ModerateSevere
2,647
1.3 Years
7.5
mg/day
All cause mortality
34% (P<0.0001)
BEST
Bucindolol*
ModerateSevere
2,708
2.0 Years
152
mg/day
All cause mortality
(p=NS)
MERIT-HF
Metoprolol
succinate#
MildModerate
3,991
1.0 Years
159
mg/day
All cause mortality
34% (P=0.0062)
MDC
Metoprolol
tartrate*
MildModerate
383
1.0 Years
108
mg/day
Death or Need for TX
(P=NS)
CAPRICORN
Carvedilol
Mild
1,989
1.3 Years
40
mg/day
All cause mortality
23% (P =0.03)
US Carvedilol
Carvedilol
MildModerate
1,094
0.5 Years
45
mg/day
All-cause mortality†
65% (P=.0001)
COPERNICUS
Carvedilol
Severe
2,289
0.9 Years
37
mg/day
All-cause mortality
35% (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)
*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
Beta-Blocker Recommendations
Secondary Prevention
I IIa IIb III
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.)
I IIa IIb III
Beta-blocker for 3 years in all patients with normal left
ventricular function who have had a MI or ACS
I IIa IIb III
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
Source: Smith SC Jr. et al. JACC 2011;58:2432-2446
Beta-Blocker Recommendations (Continued)
I IIa IIb III
Secondary Prevention
Beta-blocker in patients with LVSD (ejection fraction <40%)
without HF or prior MI
I IIa IIb III
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
Source: Smith SC Jr. et al. JACC 2011;58:2432-2446