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AHA/ACC Guidelines for Secondary AHA/ACC Guidelines for Secondary Prevention for Patients with Coronary Prevention for Patients with Coronary
and Other Atherosclerotic Vascular and Other Atherosclerotic Vascular Disease: 2006 UpdateDisease: 2006 Update
Gregg C. Fonarow, MD and Sidney Smith Jr, MD on behalf of the Secondary Prevention Writing Group
3
IntroductionIntroduction
This slide set was adapted from the AHA/ACC Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2006 Update
The full-text guidelines are available on the Web sites of the AHA (www.americanheart.org) and the ACC (www.acc.org)
Circulation 2006;113:2363-2372 and J Am Coll Cardiol 2006;47:2130-2139
4
IntroductionIntroduction
• Since the 2001 update of the AHA/ACC consensus statement on secondary prevention, important evidence from clinical trials has emerged that further supports and broadens the merits of aggressive risk reduction therapies
• This growing body of evidence confirms that aggressive comprehensive risk factor management improves survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life
• The secondary prevention patient population includes those with established coronary and other atherosclerotic vascular disease, including peripheral arterial disease, atherosclerotic aortic disease and carotid artery disease.
5
AHA Secondary Prevention for Patients with AHA Secondary Prevention for Patients with Coronary Artery and Other Atherosclerotic Coronary Artery and Other Atherosclerotic
Vascular Disease Writing Committee MembersVascular Disease Writing Committee Members
Sidney C. Smith, Jr, MD; Jerilyn Allen, RN, ScD; Steven N. Blair, Sidney C. Smith, Jr, MD; Jerilyn Allen, RN, ScD; Steven N. Blair, PED; Robert O. Bonow, MD; Lawrence M. Brass, MD; Gregg C. PED; Robert O. Bonow, MD; Lawrence M. Brass, MD; Gregg C. Fonarow, MD; Scott M. Grundy, MD, PhD; Loren Hiratzka, MD ; Fonarow, MD; Scott M. Grundy, MD, PhD; Loren Hiratzka, MD ; Daniel Jones, MD; Harlan M. Krumholz, MD; Lori Mosca, MD, PhD, Daniel Jones, MD; Harlan M. Krumholz, MD; Lori Mosca, MD, PhD, MPH; Richard C. Pasternak, MD*; Thomas Pearson, MD, MPH, MPH; Richard C. Pasternak, MD*; Thomas Pearson, MD, MPH, PhD; Marc A. Pfeffer, MD, PhD; Kathryn A. Taubert, PhDPhD; Marc A. Pfeffer, MD, PhD; Kathryn A. Taubert, PhD
*Dr. Pasternak withdrew from the Writing Group on June 22nd, 2004, when he accepted an offer of employment as Vice President, Clinical Research, Cardiovascular and Atherosclerosis at Merck Research Laboratories.
Circulation 2006;113:2363-2372 and J Am Coll Cardiol 2006;47:2130-2139
6
Class I
Benefit >>> Risk
Procedure or treatment SHOULD
be performed or administered
Class IIa
Benefit >> RiskAdditional studies
with focused objectives needed
IT IS REASONABLE to perform
procedure or administer treatment
Class IIb
Benefit ≥ RiskAdditional studies
with broad objectives needed; Additional registry
data would be helpful
Procedure or treatment MAY BE
CONSIDERED
Class III
Risk ≥ BenefitNo additional studies
needed
Procedure or treatment should
NOT be performed or administered SINCE IT IS NOT HELPFUL
AND MAY BE HARMFUL
Applying Classification of Applying Classification of Recommendations and Level of Recommendations and Level of EvidenceEvidence
7
Level A
Multiple (3-5) population risk strata evaluated
General consistency of direction and magnitude of
effect
Class I
Recommendation that procedure or treatment is
useful/ effective
Sufficient evidence from
multiple randomized
trials or meta-analyses
Class IIa
Recommendation in favor of
treatment or procedure being useful/ effective
Some conflicting evidence from
multiple randomized
trials or meta-analyses
Class IIb
Recommendation’s usefulness/ efficacy less
well established
Greater conflicting
evidence from multiple
randomized trials or meta-
analyses
Class III
Recommendation that procedure
or treatment not useful/ effective
and may be harmful
Sufficient evidence from
multiple randomized
trials or meta-analyses
Applying Classification of Applying Classification of Recommendations and Level of Recommendations and Level of EvidenceEvidence
8
Level B
Limited (2-3) population risk strata evaluated
Class I
Recommen-dation that
procedure or treatment is
useful/ effective
Limited evidence from single randomized trial or non-randomized
studies
Class IIa
Recommen-dation in favor of
treatment or procedure being useful/ effective
Some conflicting evidence from
single randomized trial
or non-randomized
studies
Class IIb
Recommen-dation’s
usefulness/ efficacy less well
established
Greater conflicting evidence from
single randomized trial
or non-randomized
studies
Class III
Recommen-dation that procedure or
treatment not useful/effective
and may be harmful
Limited evidence
from single randomized trial
or non-randomized
studies
Applying Classification of Applying Classification of Recommendations and Level of Recommendations and Level of Evidence Evidence
9
Applying Classification of Applying Classification of Recommendations and Level of Recommendations and Level of Evidence Evidence
Level C
Very limited (1-2) population risk strata evaluated
Class I
Recommen-dation that
procedure or treatment is
useful/ effective
Only expert opinion, case
studies, or standard-of-
care
Class IIa
Recommendation in favor of
treatment or procedure being useful/effective
Only diverging expert opinion, case studies, or standard-of-care
Class IIb
Recommen-dation’s
usefulness/ efficacy less well
established
Only diverging expert opinion, case studies, or standard-of-care
Class III
Recommendation that procedure or
treatment not useful/effective
and may be harmful
Only expert opinion, case
studies, or standard-of-care
10
Secondary Prevention DefinitionSecondary Prevention Definition
• Therapy to reduce recurrent cardiovascular events and decrease cardiovascular mortality in patients with established atherosclerotic vascular disease
• Patients covered include those with established coronary and other atherosclerotic vascular disease, including peripheral arterial disease, atherosclerotic aortic disease and carotid artery disease
• Individuals with sub-clinical atherosclerosis and patients whose only manifestation is diabetes are covered in other guidelines
11
Components of Secondary Components of Secondary PreventionPrevention
Cigarette smoking cessationCigarette smoking cessationBlood pressure controlBlood pressure controlLipid management to goalLipid management to goalPhysical activityPhysical activityWeight management to goalWeight management to goalDiabetes management to goalDiabetes management to goal
Antiplatelet agents / anticoagulantsAntiplatelet agents / anticoagulants
Renin angiotensin aldosterone system blockersRenin angiotensin aldosterone system blockers
Beta blockersBeta blockers
Influenza vaccinationInfluenza vaccination
12
Evidence Based TherapiesEvidence Based Therapies
The writing group emphasizes the importance of giving consideration to the use of cardiovascular medications that have been proven to be of benefit in randomized clinical trials.
This approach strengthens the evidence-based foundation for therapeutic application of these guidelines.
The committee acknowledges that in many trials there isunder-representation of ethnic minorities, women, and the elderly.
13
Goal: Complete Cessation and No Exposure to Environmental
Tobacco Smoke
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Cigarette Smoking Cigarette Smoking RecommendationsRecommendations
•Ask about tobacco use status at every visit.
•Advise every tobacco user to quit.
•Assess the tobacco user’s willingness to quit.
•Assist by counseling and developing a plan for quitting.
•Arrange follow-up, referral to special programs, or pharmacotherapy (including nicotine replacement and bupropion.
•Urge avoidance of exposure to environmental tobacco smoke at work and home.
14
0.1 1.0 10Ceased smoking Continued smoking
RR (95% Cl)Study
Aberg, et al. 1983 0.67 (0.53-0.84)
Herlitz, et al. 1995 0.99 (0.42-2.33)
Johansson, et al. 1985 0.79 (0.46-1.37)
Perkins, et al. 1985 3.87 (0.81-18.37)
Sato, et al. 1992 0.10 (0.00-1.95)
Sparrow, et al. 1978 0.76 (0.37-1.58)
Vlietstra, et al. 1986 0.63 (0.51-0.78)
Voors, et al. 1996 0.54 (0.29-1.01)
Cigarette Smoking Cessation: Risk Cigarette Smoking Cessation: Risk of Non-fatal MI*of Non-fatal MI*
Critchley JA et al. JAMA. 2003;290:86-97.
*Includes those with known coronary heart disease CI=Confidence interval, RR=Relative risk
15
Ask and document pt’stobacco use status
Advise: Provide a strong, personalizedmessage to quit using tobacco
Assess* readiness to quit in next 30 days
Prevent Relapse• Congratulate successes• Encourage to remain tobacco-free• Discuss benefits experienced by patient• Address weight gain, negative mood, and lack of support
Increase Motivation• Relevance to patients personal situation• Risks: short and long term, environmental• Rewards: potential benefits of quitting• Roadblocks: identify barriers and potential solutions• Repetition: repeat motivational intervention• Reassess readiness to quit
Assist • Negotiate a plan • STAR**• Discuss pharmacotherapy• Social support• Provide educational materials
Arrange follow-up to check plan or adjust meds• Call right before and after quit date• Weekly follow-up x 2 weeks, then monthly x 6 months• Ask about difficulties (withdrawal, depressed mood)• Build upon successes• Seek commitment to stay tobacco-free
**STARSet quit dateTell family, friends, and coworkers about itAnticipate challenges: withdrawal, breaksRemove tobacco from the house, car, and social life
Recent Quitter(<6 months)
Current User
Not Ready
Ready
Smoking Cessation AlgorithmSmoking Cessation Algorithm
Treating Tobacco Use and Dependence: A Clinical Practice Guideline, U.S. Department of Health and Human Services, June 2000
16
Smoking Cessation Smoking Cessation Pharmacotherapy*Pharmacotherapy*
Agent Caution Side Effects
Dosage Duration Instructions
Bupropion SR(Zyban®)
Seizure disorderEating disorder
Taking MAO inhibitor
Pregnancy
InsomniaDry mouth
150 mg QAMthen
150 mg BID
3 days
Maintenance (8 weeks, but may be used
up to 6 months)
Start 1-2 weeks before quit date.
Take second dose in early afternoon or decrease to 150
mg QAM for insomnia.
TransdermalNicotinePatch**
Within 2 weeks of a MI
Unstable anginaArrhythmias
Decompensated heart failure
Skin reactionInsomnia
21 mg QAM14 mg QAM 7 mg QAM
or15 mg QAM
4 weeks2 weeks2 weeks
8 weeks
Apply to different hairless site daily.
Remove before bed for insomnia.Start at <15 mg for
<10 cigs/day
*Pharmacotherapy combined with behavioral support provides the best success rate
**Other nicotine replacement therapy options include: nicotine gum, lozenge, inhaler, nasal spray
17
Goal: <140/90 mm Hg or <130/80 if diabetes or chronic kidney disease
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Blood Pressure Control Blood Pressure Control RecommendationsRecommendations
Blood pressure 120/80 mm Hg or greater:
Initiate or maintain lifestyle modification: weight control, increased physical activity, alcohol moderation, sodium reduction, and increased consumption of fresh fruits vegetables and low fat dairy products
Blood pressure 140/90 mm Hg or greater (or 130/80 or greater for chronic kidney disease or diabetes)
As tolerated, add blood pressure medication, treating initially with beta blockers and/or ACE inhibitors with addition of other drugs such as thiazides as needed to achieve goal blood pressure
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
18
Prospective Studies Collaboration. Lancet. 2002;360:1903-1913
Usual Diastolic BP (mm Hg)Usual Systolic BP (mm Hg)
Isch
emic
Hea
rt D
isea
se M
ort
alit
y
50-59
60-69
70-79
80-89Age 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
Blood Pressure: Lower is BetterBlood Pressure: Lower is Better
Isch
emic
Hea
rt D
isea
se M
ort
alit
y
Ischemic Heart Disease Mortality
BP=Blood pressure
19
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
Total
0 0.5 1.0 1.5 2.0
0.79 (0.69 to 0.90)
He J et al. Am Heart J 1999; 138:211-219
Better than placebo Worse than placebo
Blood Pressure: Risk of CHD with Blood Pressure: Risk of CHD with Active TreatmentActive Treatment
CHD=Coronary heart disease
20
Yes >100 >160 Stage 2 Hypertension
Yes 90–99 140–159 Stage 1 Hypertension
Yes 80–89 120–139 Pre-hypertension
Encourage <80 <120 Normal
With compelling indications
Initial drug therapy Lifestyle
modificationDBP* mmHg
SBP* mmHg
BP classification
JNC VII Guidelines for Management JNC VII Guidelines for Management and Treatmentand Treatment
ACEI=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=-blocker, BP=Blood pressure, CCB=Calcium channel blocker, DBP=Diastolic blood pressure, SBP=Systolic blood pressure
Chobanian AV et al. JAMA. 2003;289:2560-2572
*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.
Drug(s) for the compelling indications.‡
Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.
Drug(s) for compelling indications. ‡
21
Modification Recommendation Approximate SBP Reduction Range
Weight reduction Maintain normal body weight (BMI=18.5-24.9)
5-20 mmHg/10 kg weight lost
Adopt 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 on most days of the week
4-9 mmHg
Moderate alcohol consumption
<2 drinks/day for men and <1 drink/day for women
2-4 mmHg
JNC VII Lifestyle Modifications for JNC VII Lifestyle Modifications for BP ControlBP Control
Chobanian AV et al. JAMA. 2003;289:2560-2572
BMI=Body mass index, SBP=Systolic blood pressure
22
Clinical-Trial BasisCompelling Indication
ALLHAT, HOPE, ANBP2,LIFE, CONVINCE
High CAD Risk
ACC/AHA Post-MI Guideline, BHAT, SAVE, Capricorn,
EPHESUS
Post-MI
MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, Val-HeFT,
RALES
Initial Therapy Options
Diuretic, BB, ACEI, CCB
BB, ACEI, Aldo Ant
Diuretic, BB, ACEI,ARB, Aldo Ant
Heart Failure
JNC VII Compelling Indications for JNC VII Compelling Indications for Drug ClassesDrug Classes
ACEI=Angiotensin converting enzyme inhibitor, Aldo Ant=Aldosterone antagonist, ARB=Angiotensin receptor blocker, BB=b-blocker, CAD=Coronary artery disease, CCB=Calcium channel blocker, MI=Myocardial Infarction
Chobanian AV et al. JAMA. 2003;289:2560-2572
Recurrent Stroke Prevention PROGRESSDiuretic, ACEI
NKF-ADA Guideline,UKPDS, ALLHAT
NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN,
AASK
Diuretic, BB, ACEI,ARB, CCB
ACEI, ARB
Diabetes Mellitus
Chronic Kidney Disease
23
Lipid Management GoalLipid Management Goal
LDL-C should be less than 100 mg/dL
Further reduction to LDL-C to < 70 mg/dL is reasonable
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
*Non-HDL-C = total cholesterol minus HDL-C
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
If TG >200 mg/dL, non-HDL-C should be < 130 mg/dL*
24
Risk Category LDL-C and non-HDL-C Goal
Initiate TLCConsider
Drug Therapy
High risk: CHD or CHD risk equivalents (10-year risk >20%)and
<100 mg/dL if TG > 200 mg/dL,non-HDL-C should be < 130 mg/dL
100 mg/dL
>100 mg/dL (<100 mg/dL: consider
drug options)
Very high risk:ACS or established CHDplus: multiple major risk factors (especially diabetes) or severe and poorly controlled risk factors
<70 mg/dL, non-HDL-C < 100
mg/dL
All patients >100 mg/dL (<100 mg/dL: consider
drug options)
Grundy, S. et al. Circulation 2004;110:227-39.
Lipid Management Goals: NCEPLipid Management Goals: NCEP
ATP=Adult Treatment Panel, CHD=Coronary heart disease, LDL-C=Low-density lipoprotein cholesterol, TLC=Therapeutic lifestyle changes
25
Lipid Management Lipid Management RecommendationsRecommendations
Start dietary therapy (<7% of total calories as saturated fat and <200 mg/d cholesterol)
Adding plant stanol/sterols (2 gm/day) and viscous fiber (>10 mg/day) will further lower LDL
Promote daily physical activity and weight management.
Encourage increased consumption of omega-3 fatty acids in fish or 1 g/day omega-3 fatty acids in capsule form for risk reduction.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
For all patients
26
*Trans fatty acids also raise LDL-C and should be kept at a low intake.Note: Regarding total calories, balance energy intake and expenditure to maintain desirable body weight.
<200 mg/dCholesterol
~15% of total caloriesProtein
20–30 g/dFiber
50%–60% of total caloriesCarbohydrate (esp. complex carbs)
25%–35% of total caloriesTotal fat
Up to 20% of total caloriesMonounsaturated fat
Up to 10% of total caloriesPolyunsaturated fat
<7% of total caloriesSaturated fat*
Recommended IntakeNutrient
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
ATP III Dietary RecommendationsATP III Dietary Recommendations
ATP=Adult Treatment Panel
27
Lipid Management Lipid Management RecommendationsRecommendations
If baseline LDL-C > 100 mg/dL, initiate LDL-lowering drug therapy
If on-treatment LDL-C > 100 mg/dL, intensify LDL-lowering drug therapy (may require LDL lowering drug combination)
If baseline is LDL-C 70 to 100 mg/dL, it is reasonable to treat to LDL < 70 mg/dL
Assess fasting lipid profile in all patients, and within 24 hours of hospitalization for those with an acute event. For patients hospitalized, initiate lipid-lowering medication as recommended below prior to discharge according to the following schedule:
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
When LDL lowering medications are used, obtain at least a 30-40% reduction in LDL-C levels.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
28
Lipid Management Lipid Management RecommendationsRecommendations
If TG are 200-499 mg/dL, non-HDL-C should be < 130 mg/dL
Further reduction of non-HDL to < 100 mg/dL is reasonable
Therapeutic options to reduce non-HDL-C: More intense LDL-C lowering therapy I (B) orNiacin (after LDL-C lowering therapy) IIa (B) orFibrate (after LDL-C lowering therapy) IIa (B)
If TG are > 500 mg/dL, therapeutic options to prevent pancreatitis are fibrate or niacin before LDL lowering therapy; and treat LDL-C to goal after TG-lowering therapy. Achieve non-HDL-C < 130 mg/dL, if possible
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
29
Baseline Baseline LDL-C (mg/dL)LDL-C (mg/dL)
Statin Statin (n = 10,269)(n = 10,269)
Placebo Placebo (n = 10,267)(n = 10,267)
<100<100 282 (16.4%)282 (16.4%) 358 (21.0%)358 (21.0%)
100–129100–129 668 (18.9%)668 (18.9%) 871 (24.7%)871 (24.7%)
130130 1083 (21.6%)1083 (21.6%) 1356 (26.9%)1356 (26.9%)
All patientsAll patients 2033 (19.8%)2033 (19.8%) 2585 (25.2%)2585 (25.2%)
Event Rate Ratio (95% CI)Statin Better Statin Worse
0.4 0.6 0.8 1.0 1.2 1.4
0.76 (0.72–0.81)P<0.0001
Heart Protection Study (HPS)
HMG-CoA Reductase Inhibitor: HMG-CoA Reductase Inhibitor: Secondary PreventionSecondary Prevention
20,536 patients with CAD, other occlusive arterial disease, or DM 20,536 patients with CAD, other occlusive arterial disease, or DM randomized to simvastatin (40 mg) or placebo for 5.5 yearsrandomized to simvastatin (40 mg) or placebo for 5.5 years
CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus,
HPS Collaborative Group. Lancet 2002;360:7-22
30
Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT)—TIMI 22 Study
3 6 9 12 15 18 21 24 27 30
Follow-up (months)
30
25
20
15
10
5
0
P =0.005
Rec
urre
nt M
I or
Car
diac
Dea
th
16% RRRAtorvastatin
Pravastatin
ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction
Cannon CP et al. NEJM 2004;350:1495-1504
HMG-CoA Reductase Inhibitor: HMG-CoA Reductase Inhibitor: Secondary PreventionSecondary Prevention
4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months
31LaRosa JC et al. NEJM. 2005;352:1425-1435
LDL-C=Low density lipoprotein cholesterol; TNT=Treating to New Targets; HPS=Heart Protection Study; CARE=Cholesterol and Recurrent Events Trial; LIPID=Long-term Intervention with Pravastatin in Ischaemic Disease; 4S=Scandinavian Simvastatin Survival Study.
30
25
20
15
10
5
00 70 90 110 130 150 170 190 210
LDL-C (mg/dL)
TNT (atorvastatin 80 mg/d)
TNT (atorvastatin 10 mg/d)HPS
CARE
LIPIDLIPID
CAREHPS
Eve
nt (
%) 4S
4SStatinPlacebo
Relationship between LDL Levels and Event Rates in Secondary Prevention Trials of Patients with Stable CHD
HMG-CoA Reductase Inhibitor: HMG-CoA Reductase Inhibitor: Secondary PreventionSecondary Prevention
32
HDL-C=High-density lipoprotein cholesterol, LDL-C=Low-density lipoprotein cholesterol, TC=Total cholesterol, TG=Triglycerides *Daily dose of 40mg of each drug, excluding rosuvastatin.
Therapy TC LDL HDL TG Patient tolerability
Statins* 19-37% 25-50% 4-12% 14-29% Good
Ezetimibe 13% 18% 1% 9% Good
Bile acid sequestrants 7-10% 10-18% 3% Neutral or
Poor
Nicotinic acid 10-20% 10-20% 14-35% 30-70% Reasonable to Poor
Fibrates 19% 4-21% 11-13% 30% Good
Lipid Management Lipid Management PharmacotherapyPharmacotherapy
33
Physical Activity RecommendationsPhysical Activity Recommendations
Assess risk with a physical activity history and/or an exercise test, to guide prescription
Encourage 30 to 60 minutes of moderate intensity aerobic activity such as brisk walking, on most, preferably all, days of the week, supplemented by an increase in daily lifestyle activities
Advise medically supervised programs for high-risk patients (e.g. recent acute coronary syndrome or revascularization, HF)
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Goal: 30 minutes 7 days/week, minimum 5 days/week
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
34
Observational study of self-reported physical activity in 772 men with Observational study of self-reported physical activity in 772 men with established coronary heart disease established coronary heart disease
Light or moderate exercise is associated with lower riskLight or moderate exercise is associated with lower risk
Wannamethee SG et al. Circulation 2000;102:1358-1363
Exercise Evidence: Mortality RiskExercise Evidence: Mortality Risk
35
Weight Management RecommendationsWeight Management Recommendations
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Goal: BMI 18.5 to 24.9 kg/m2Waist Circumference: Men: < 40 inches Women: < 35 inches
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Assess BMI and/or waist circumference on each visit and consistently encourage weight maintenance/ reduction through an appropriate balance of physical activity, caloric intake, and formal behavioral programs when indicated.
If waist circumference (measured at the iliac crest) >35 inches in women and >40 inches in men initiate lifestyle changes and consider treatment strategies for metabolic syndrome as indicated.
The initial goal of weight loss therapy should be to reduce body weight by approximately 10 percent from baseline. With success, further weight loss can be attempted if indicated.
*BMI is calculated as the weight in kilograms divided by the body surface area in meters2. Overweight state is defined by BMI=25-30 kg/m2. Obesity is defined by a BMI >30 kg/m2.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
36
Mhurchu N et al. Int J Epidemiol 2004;33:751-758
0.5
1.0
2.0
4.0
16 20 24 28 32 36
Body Mass Index (kg/m2)*
Haz
ard
Rat
io
0.5
1.0
2.0
4.0
16 20 24 28 32 36
0.5
1.0
2.0
4.0
16 20 24 28 32 36
HemorrhagicStroke
IschemicStroke
Ischemic HeartDisease
CV Risk Increases with Body Mass CV Risk Increases with Body Mass IndexIndex
CV=Cardiovascular
Body mass index is calculated as the weight in kilograms divided by the body surface area in meters2.
37Grundy, et al. Diagnosis and management of the metabolic syndrome: an
AHA/NHLBI Scientific Statement. Circulation 2005;112:2735-2752.
Risk Factor Defining Level
Waist circumference (abdominal obesity)
>40 in (>102 cm) in men
>35 in (>88 cm) in women
Triglyceride level >150 mg/dl
HDL-C level <40 mg/dl in men
<50 mg/dl in women
Blood pressure >130/>85 mmHg
Fasting glucose >100 mg/dl
Definition of the Metabolic SyndromeDefinition of the Metabolic Syndrome
Defined by presence of >3 risk factors
HDL-C=High-density lipoprotein cholesterol
38
3,234 patients with elevated fasting and post-load glucose levels 3,234 patients with elevated fasting and post-load glucose levels randomized to placebo, metformin (850 mg twice daily), or lifestyle randomized to placebo, metformin (850 mg twice daily), or lifestyle
modification* for 2.8 yearsmodification* for 2.8 years
Lifestyle modification reduces the risk of developing DMLifestyle modification reduces the risk of developing DM
Metabolic Syndrome: Risk of Metabolic Syndrome: Risk of Developing DMDeveloping DM
Diabetes Prevention Program (DPP)
Knowler WC et al. NEJM 2002;346:393-403
*Includes 7% weight loss and at least 150 minutes of physical activity per week
Placebo
Metformin
Lifestyle modification
Inci
denc
e of
DM
(%
)
20
40
0 1 42 3
39
Diabetes Mellitus Recommendations
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Goal: Hb A1c < 7%
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Lifestyle and pharmacotherapy to achieve near normal HbA1C (<7%).
Vigorous modification of other risk factors (e.g., physical activity, weight management, blood pressure control, and cholesterol management as recommended).
Coordinate diabetic care with patient’s primary care physician or endocrinologist. )
HbA1c = Glycosylated hemoglobin
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
40
Antiplatelet Agents / Anticoagulation Antiplatelet Agents / Anticoagulation RecommendationsRecommendations
41
Aspirin RecommendationsAspirin Recommendations
Start and continue indefinitely aspirin 75 to 162 mg/d in all patients unless contraindicated
For patients undergoing CABG, aspirin (100 to 325 mg/d) should be started within 48 hours after surgery to reduce saphenous vein graft closure
Post-PCI-stented patients should receive 325 mg per day of aspirin for 1 month for bare metal stent, 3 months for sirolimus-eluting stent and 6 months for paclitaxel-eluting stent
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
42
Start and continue clopidogrel 75 mg/d in combination with aspirin
for post ACS or post PCI with stent placement patients for up to 12 months
for post PCI-stented patients>1 month for bare metal stent, >3 months for sirolimus-eluting stent >6 months for paclitaxel-eluting stent
*Clopidogrel is generally given preference over Ticlopidine because of a superior safety profile
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Clopidogrel RecommendationsClopidogrel Recommendations
43
Anticoagulation RecommendationsAnticoagulation Recommendations
Manage warfarin to international normalized ratio 2.0 to 3.0 for paroxysmal or chronic atrial fibrillation or flutter, and in post-MI patients when clinically indicated (e.g., atrial fibrillation, LV thrombus.)
Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with increased risk of bleeding and should be monitored closely
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
44
Aspirin Evidence: Secondary Aspirin Evidence: Secondary PreventionPrevention
Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86.
Category % Odds Reduction
Acute myocardial infarction
Acute stroke
Prior myocardial infarction
Prior stroke/transient ischemic attack
Other high risk
Coronary artery disease(e.g. unstable angina, heart failure)
Peripheral arterial disease(e.g. intermittent claudication)
High risk of embolism (e.g. atrial fibrillation)
Other (e.g. diabetes mellitus)
All trials
1.00.50.0 1.5 2.0 Control better Antiplatelet better
Effect of antiplatelet therapy* on vascular events**
*Aspirin was the predominant antiplatelet agent studied**Vascular events include MI, stroke, or death
45
Aspirin Evidence: Dose and Aspirin Evidence: Dose and EfficacyEfficacy
0.5 1.0 1.5 2.0
500-1500 mg 34 19
160-325 mg 19 26
75-150 mg 12 32
<75 mg 3 13
Any aspirin 65 23
Antiplatelet Better Antiplatelet Worse
Aspirin Dose No. of Trials (%)Odds Ratio for
Vascular Events
0
P<.0001
Indirect Comparisons of Aspirin Doses on Vascular Events in High-Risk Patients
Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86
46
Clopidogrel Evidence: ACS Clopidogrel Evidence: ACS (Non-STEMI and UA)(Non-STEMI and UA)
Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial
The CURE Trial Investigators. NEJM. 2001;345:494-502
NSTEMI-ACS=Non ST-segment elevation acute coronary syndrome
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
3 6 90 12
Rat
e of
dea
th,
myo
card
ial i
nfar
ctio
n,
or s
trok
e
P<0.001
Months of Follow Up
Aspirin + Clopidogrel
Aspirin + Placebo
12,562 patients with a NSTEMI-ACS randomized to daily aspirin (75-325 mg) or clopidogrel (300 mg load, 75 mg thereafter) plus
aspirin (75-325 mg) for 3-12 months (average 9 months)
47Steinhubl S et al. JAMA 2002; 288:2411-20
Clopidogrel for the Reduction of Events during Observation (CREDO) Trial
Clopidogrel Evidence: Post PCIClopidogrel Evidence: Post PCI
DAP=Dual antiplatelet therapy, PCI=Percutaneous coronary intervention, RRR=Relative risk reduction
*Dual antiplatelet therapy=Aspirin (75-325 mg daily) plus Clopidogrel (300 mg load followed by 75 mg daily).
0 123 6 90
Ris
k of
MI,
Str
oke,
or
Dea
th (
%)
27% RRR, P=0.02
10
5
15 4 weeks of DAP1 year of DAP
Months from Randomization
22,116 patients undergoing PCI randomized to 4 weeks of DAP* followed by aspirin (75-325 mg) monotherapy vs persistent DAP* for 1 year
48
Renin-Angiotensin-Aldosterone Renin-Angiotensin-Aldosterone System Blockers RecommendationsSystem Blockers Recommendations
49
ACE Inhibitor RecommendationsACE Inhibitor Recommendations
Use in all patients with LVEF < 40%, and those with diabetes or chronic kidney disease indefinitely, unless contraindicated
Consider for all other patients
Among lower risk patients with normal LVEF where cardiovascular risk factors are well controlled and where revascularization has been performed, their use may be considered optional
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
ACE=Angiotensin converting enzyme, LVEF= left ventricular ejection fraction
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
50
Angiotensin Receptor Blocker Angiotensin Receptor Blocker RecommendationsRecommendations
Use in patients who are intolerant of ACE inhibitors with HF or post MI with LVEF less than or equal to 40%.
Consider in other patients who are ACE inhibitor intolerant.
Consider use in combination with ACE inhibitors in systolic dysfunction HF.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
ACE=Angiotensin converting enzyme inhibitor, LVEF=Left Ventricular Ejection fraction, HF=Heart failure, MI=Myocardial infarction
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
51
Aldosterone Antagonist Aldosterone Antagonist RecommendationsRecommendations
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII Use in post MI patients, without significant renal dysfunction or hyperkalemia, who are already receiving therapeutic doses of an ACE inhibitor and beta blocker, have an LVEF < 40% and either diabetes or heart failure
ACE=Angiotensin converting enzyme inhibitor, LVEF=Left Ventricular Ejection fraction, MI=Myocardial infarction
*Contraindications include abnormal renal function (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) and hyperkalemia (K+ >5.0 meq/L)
52
Years
Pro
babili
ty o
f Event
0
0.05
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)0.1
Flather MD, et al. Lancet. 2000;355:1575–1581
SAVERadionuclideEF 40%
AIREClinical and/or radiographic signs of HF
TRACEEchocardiogramEF 35%
ACE Inhibitor Evidence: Post MI ACE Inhibitor Evidence: Post MI with LVD or HFwith LVD or HF
ACE-I=Angiotensin converting enzyme inhibitors, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio
53
ACE Inhibitor Evidence: CAD, CVD, ACE Inhibitor Evidence: CAD, CVD, PVD or DMPVD or DM
Days of Follow-Up
CV
dea
th, M
I, or
st
roke
(%
)
22% RRR, P<0.0010.00
0.05
0.10
0.15
0.20
0 500 1000 1500
Placebo
Ramipril
HOPE Investigators. NEJM 2000;342:145-153
Heart Outcomes Prevention and Evaluation (HOPE) Study
ACE-I=Angiotensin converting enzyme inhibitors, DM=Diabetes mellitus, CV=Cardiovascular, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction
9,9,297 patients with DM or vascular disease plus one additional CV risk factor, but without HF or known LVSD randomized to ramipril (10
mg) or placebo for 5 years
54
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)
ACE Inhibitor Evidence: CADACE Inhibitor Evidence: CAD
European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA)
Favors Perindopril Favors Placebo
EUROPA Investigators. Lancet 2003;362:782-788
13,655 patients with CAD and presumed normal left ventricular 13,655 patients with CAD and presumed normal left ventricular function randomized to perindopril (8 mg) or placebo for 4.2 yearsfunction randomized to perindopril (8 mg) or placebo for 4.2 years
ACE-I=Angiotensin converting enzyme inhibitors, CAD=Coronary artery disease, CV=Cardiovascular, MI=Myocardial infarction
55
ACE Inhibitor Evidence: CADACE Inhibitor Evidence: CAD
Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial
Prim
ary
End
Poi
nt (
%)*
30
25
20
15
10
5
00 1 2 3 4 5 6
Years After Randomization
PlaceboTrandolapril
PEACE Trial Investigators. NEJM 2004;351:2058-2068
*Includes death from cardiovascular causes, myocardial infarction, or coronary revascularization
8,290 patients with stable coronary artery disease and normal left ventricular function randomized to trandolapril (4 mg) or placebo for
4.8 years
56
ACE Inhibitor Evidence: ACE Inhibitor Evidence:
Secondary PreventionSecondary PreventionComparison between the HOPE and PEACE trials
Braunwald, E. et al., NEJM 2004;351:2058-68.
CHD=Coronary heart disease, MI=Myocardial infarction
*Reflects greater blood pressure control, revascularization, and use of other risk-reducing medications (i.e., antiplatelet therapy, -blocker, lipid-lowering medication)
0
5
10
15
20
0 1 2 3 4 5
HOPE, placebo
HOPE, active drug (ramipril)
PEACE, placebo
MI,
Car
diac
dea
th,
or S
trok
e (%
)
Years
57
ARB Evidence: Post MI with LVD ARB Evidence: Post MI with LVD or HFor HF
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
Cau
se M
orta
lity
Months
Valsartan vs. Captopril: HR = 1.00; P = 0.982
Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726
EF=Ejection fraction, HR=Hazard ratio, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, RAS=Renin angiotensin system
14,703 patients with post-MI HF or LVSD (EF <0.40) randomized to captopril (50 mg three times daily), valsartan (160 mg twice daily), or captopril (50 mg three times daily) plus valsartan (80 mg twice daily)
over 2 years
58
ARB Evidence: Heart FailureARB Evidence: Heart Failure
Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Alternative Trial
Granger CB et al. Lancet. 2003;362:772-777
ACE-I=Angiotensin converting enzyme inhibitors, ARB=Angiotensin receptor blockers, EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction
0 1 2 3Years
50
HR 0.77 p=0.00040
40
30
20
10
Candesartan
Placebo
CV
Dea
th o
f H
ospi
taliz
atio
n fo
r H
F
2,028 patients with symptomatic HF, LVSD (EF <40%), and intolerance to ACE-I randomized to candesartan (32 mg) or
placebo over 34 months
59
ARB Evidence: Heart FailureARB Evidence: Heart Failure
0 1 2 3
0
10
20
30
40
50
3.5
HR 0.85, p=0.011
Candesartan
Placebo
CV
Dea
th o
f H
ospi
taliz
atio
n fo
r H
F
Years
Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Added Trial
ACE-I=Angiotensin converting enzyme inhibitors, ARB=Angiotensin receptor blockers, EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, RAS=Renin angiotensin system
McMurray JJ et al. Lancet. 2003;362:767-71
2,548 patients with symptomatic HF and LVSD (EF <40%) randomized to candesartan (32 mg) or placebo in addition to
an ACE-I over 34 months
60Pitt B et al. NEJM 1999;341:709-717
Aldosterone Antagonist: Heart Aldosterone Antagonist: Heart FailureFailure
Randomized Aldactone Evaluation Study (RALES)
EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NYHA=New York Heart Association
RR = 0.70, P<0.001
Months
Sur
viva
l (%
)
3633302724211815129630
1.00
.90
.80
.70
.60
.50
0
SpironolactonePlacebo
1,663 patients with NYHA Class III or IV HF and LVSD (EF <0.35) randomized to spironolactone (25 mg) or
placebo (50 mg) for 24 months
61
Aldosterone Antagonist: Post MI HF Aldosterone Antagonist: Post MI HF and LVSDand LVSD
Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)
RR = 0.85, P=0.008
6 12 18 24 30 360
5
10
15
20
25
0
All
Cau
se M
orta
lity
(%)
Month
EplerenonePlacebo
6,644 patients with evidence of heart failure and LVSD (EF <0.40) after a MI randomized to eplerenone (50 mg) or placebo for 16 months
Pitt B et al. NEJM 2003;348:1309-21
EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction
62
-blocker Recommendations-blocker Recommendations
63
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIIIStart and continue indefinitely in all post MI, ACS, LV dysfunction with or without HF symptoms, unless contraindicated.
Consider chronic therapy for all other patients with coronary or other vascular disease or diabetes unless contraindicated.
*Precautions but still indicated include mild to moderate asthma or chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds.
MI=Myocardial infarction, HF=Heart Failure
-blocker Recommendations-blocker Recommendations
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
64
Phase of Treatment
Acute treatment
Secondaryprevention
Overall
Total #Patients
28,970
24,298
53,268
0.5 1.0 2.0RR of death
-blockerbetter
RR (95% CI)
Placebobetter
0.87 (0.77-0.98)
0.77 (0.70-0.84)
0.81 (0.75-0.87)
-blocker Evidence-blocker Evidence
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 -blocker Therapy
CI=Confidence interval, RR=Relative risk
65
6,644 patients with LVEF <0.40 after a MI with or without HF randomized to carvedilol or placebo for 24 months
The CAPRICORN Investigators. Lancet. 2001;357:1385–1390.
RR 0.77 P=.03
0.7
0.75
0.8
0.85
0.9
0.95
1
0 0.5 1 1.5 2 2.5
Carvedilol
Placebo
Years
Pro
po
rtio
n E
ven
t-fr
ee
n=975
n=984
-blocker Evidence: Post MI with -blocker Evidence: Post MI with Left Ventricular DysfunctionLeft Ventricular Dysfunction
Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN)
66
Study Drug
HF Severity
Patients (n)
Follow-up (years)
Mean Dosage
Effects on Outcomes
CIBIS Bisoprolol* Moderate-Severe
641 1.9 3.8 mg/day
All cause mortality 22% (p=NS)
CIBIS-II Bisoprolol* Moderate-Severe
2,647 1.3 7.5mg/day
All cause mortality34% (P<0.0001)
BEST Bucindolol* Moderate-Severe
2,708 2.0 152mg/day
All cause mortality 10% (p=NS)
MERIT-HF Metoprolol succinate#
Mild-Moderate
3,991 1.0 159mg/day
All cause mortality34% (P=0.0062)
MDC Metprolol tartrate*
Mild-Moderate
383 1.0 108mg/day
Death or Need for Tx 30% (P=NS)
CAPRICORN Carvedilol Mild 1,989 1.3 40mg/day
All cause mortality 23% (P =0.03)
US Carvedilol Carvedilol Mild-Moderate
1,094 0.5 45mg/day
All-cause mortality†
65% (P=.0001)
COPERNICUS Carvedilol Severe 2,289 0.9 37mg/day
All-cause mortality35% (P =0.0014)
-blocker Evidence: Benefit in HF -blocker Evidence: Benefit in HF and LVSDand LVSD
*Not an approved indication†Not a planned end point. #Not approved for severe HF or mortality reduction alone
67
Influenza VaccinationInfluenza Vaccination
Patients with cardiovascular disease should have influenza vaccination
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
68
Influenza Vaccination EvidenceInfluenza Vaccination Evidence
Community cohort of 140,055 subjects in the 1998–1999 season of which 55.5 % were immunized.Nichol et al. N Engl J Med 2003;348:1322-32.
Hospitalization
VaccinatedSubjects
(N=77,738)
UnvaccinatedSubjects
(N=62,317)
Adjusted Odds Ratio P value
Pneumonia or influenza 495 (0.6) 581 (0.9)0.68
(0.60–0.78)<0.001
Cardiac disease 888 (1.1) 1026 (1.6)0.81
(0.73–0.89)<0.001
Ischemic heart disease 457 (0.6) 535 (0.9)0.80
(0.70–0.91)0.001
Heart failure 466 (0.6) 538 (0.9)0.81
(0.70–0.92)0.002
Cerebrovascular disease 398 (0.5) 427 (0.7)0.84
(0.72–0.97)0.018
Death 943 (1.2) 1361 (2.2)0.52
(0.47–0.57)<0.001
Hospitalization or death 2387 (3.1) 2910 (4.7)0.65
(0.62–0.70)<0.001
Effectiveness of Influenza Vaccination during the Influenza Seasons
69
The Need to Implement Secondary The Need to Implement Secondary PreventionPrevention
Multiple studies of the use of these recommended therapies in appropriate patients continue to show that many patients in whom therapies are indicated are not receiving them in actual clinical practice.
The AHA and ACC urge that in all medical care settings where these patients are managed that programs to provide practitioners with useful reminder clues based on the guidelines, and continuously assess the success achieved in providing these therapies to the patients who can benefit from them be implemented.
Encourage that the AHA’s Get With the Guidelines and/or ACC’s Guidelines Applied to Practice Programs be instituted to identify appropriate patients for therapy
70
AHA GWTG ProgramAHA GWTG Program
GWTG is a national initiative of the AHA to improve guidelines adherence in patients hospitalized with cardiovascular disease.
GWTG uses collaborative learning sessions, conference calls, e-mail and staff support to assist hospital teams improve acute and secondary prevention care systems.
A web-based Patient Management Tool is used for point of care data collection and decision support, on-demand reporting, communication and patient education.
71
Demographics 6 clicks
Clinical/Lab 8 clicks
Dischargemeds and interventions 7 clicks
Interactivelychecks patient’sdata with theAHA guidelines
SIMPLE, ONE PAGE, ON-LINE FORM SIMPLE, ONE PAGE, ON-LINE FORM
©2001 Outcome Sciences, Inc.
72
Impact of AHA Get With The Impact of AHA Get With The Guidelines-CAD Program on Guidelines-CAD Program on Quality of CareQuality of Care
93
79
64 6757
95
83
6570 70
9787
6573 76
9687
6775 75
9791
6874
82
0102030405060708090
100
Aspirin Beta Blocker ACE Inhibitor Lipid Rx SmokingCessation
Baseline Q1 Q2 Q3 Q4
* ***
* p< 0.05 compared to baseline* *
*** * *
*
GWTG-CAD: 123 US Hospitals n=27,825Labresh, Fonarow et al. Circulation 2003;108:IV-722
**
73
AHA Secondary Prevention for Patients AHA Secondary Prevention for Patients with Coronary Artery and Other with Coronary Artery and Other Atherosclerotic Vascular DiseaseAtherosclerotic Vascular Disease
Circulation 2006;113:2363-2372 and J Am Coll Cardiol 2006;47:2130-2139
74
• Evidence confirms that aggressive comprehensive risk factor management improves survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life for these patients.
• Every effort should be made to ensure that patients are treated with evidence-based, guideline recommended, life-prolonging therapies in the absence of contraindications or intolerance.
Secondary Prevention ConclusionsSecondary Prevention Conclusions
75