the evidence for current cardiovascular disease prevention guidelines: other cardiovascular...

The Evidence for Current Cardiovascular Disease

Prevention Guidelines:

Other Cardiovascular Therapies and

Areas with Room for Improvement

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

Evidence for Current Cardiovascular Evidence for Current Cardiovascular Disease Disease

Prevention GuidelinesPrevention Guidelines

Vaccination Evidence Vaccination Evidence and Guidelinesand Guidelines

Source: Nichol KL et al. NEJM 2003;348:1322-1332

Adverse Outcome

Vaccinated

Subjects

(N=77,738)

Unvaccinated

Subjects

(N=62,317)

Adjusted Odds Ratio

P value

Hospitalization for CHD 457 (0.6) 535 (0.9) 0.80 0.001

Hospitalization for HF 466 (0.6) 538 (0.9) 0.81 0.002

Hospitalization for CVD 398 (0.5) 427 (0.7) 0.84 0.018

Death 943 (1.2) 1361 (2.2) 0.52 <0.001

Hospitalization or death 2387 (3.1) 2910 (4.7) 0.65 <0.001

286,383 community-dwelling members aged >65 years of 3 large managed-care organizations evaluated for 1-2 yrs

Influenza vaccination reduces the rate of adverse CV events

Influenza Vaccination:Influenza Vaccination:Primary PreventionPrimary Prevention

CV=Cardiovascular

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

ADA=American Diabetes Association

• An influenza vaccine should be provided to all diabetic patients >6 months of age annually.

• A pneumococcal polysaccharide vaccine should be administered to all diabetic patients >2 years of age. A one-time revaccination is recommended for individuals >64 years of age that were previously immunized at <65 years of age, if the vaccine was administered >5 years ago. Other indications for repeat vaccination include nephrotic syndrome, chronic renal disease, and other immunocompromised states, such as after transplantation.

ADA Immunization RecommendationsADA Immunization Recommendationsfor Patients with Diabetes Mellitusfor Patients with Diabetes Mellitus

Primary Prevention

Patients with cardiovascular disease should have an annual influenza vaccination

I IIa IIb III

Influenza Vaccination GuidelinesInfluenza Vaccination Guidelines

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

Secondary Prevention



Ejection Fraction Evidence Ejection Fraction Evidence and Guidelinesand Guidelines

Source: Burns RJ et al. JACC 2002;39:30-36

LV EF=Left ventricular ejection fraction, MI=Myocardial infarction, RNA=Radionuclide angiography, SPECT=Single photon emission computed tomography

1,181 patients with myocardial infarction treated with fibrinolytic therapy that underwent SPECT and RNA to evaluate LV EF

LV EF assessed after MI is predictive of mortality at 6 months

Relationship Between Ejection Relationship Between Ejection FractionFractionPost Myocardial Infarction and Post Myocardial Infarction and MortalityMortality

Echocardiography in those following a STEMI to re-evaluate ventricular function when results are used to guide treatment†

Echocardiography or radionuclide angiography in those following a NSTE-ACS when results are used to guide treatment‡

Ejection Fraction GuidelinesEjection Fraction Guidelines

I IIa IIb III

NSTE-ACS=Non-ST-segment elevation acute coronary syndrome, STEMI=ST-segment elevation myocardial infarction

Sources: †Antman EM et al. JACC 2004;44:671-719

‡Anderson JL et al. JACC 2007;50:652-726




Aldosterone Antagonist Evidence Aldosterone Antagonist Evidence and Guidelinesand Guidelines

Aldosterone

Sodium and Water

Retention

Edema

Potassium and Magnesium Excretion

Arrhythmias

Collagen deposition

Myocardial and Vascular Fibrosis

Aldosterone Antagonist:Aldosterone Antagonist:Mechanisms of ActionMechanisms of Action

Source: Pitt B et al. NEJM 1999;341:709-717

RR = 0.70, P<0.001

Months

Su

rviv

al (

%)

3633302724211815129630

1.00

.90

.80

.70

.60

.50

0

Randomized Aldactone Evaluation Study (RALES)

EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NYHA=New York Heart Association

Spironolactone

Placebo

Aldosterone Antagonist:Aldosterone Antagonist:Secondary PreventionSecondary Prevention

1,663 patients with NYHA Class III or IV HF and LVSD (EF <0.35) randomized to spironolactone (25-50mg) or placebo for 24 months

Aldosterone inhibition improves survival in patients with advanced heart failure

RR = 0.85, P=0.008

6 12 18 24 30 360

5

10

15

20

25

0

All

Cau

se M

ort

alit

y (%

)

Month

Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)

Placebo

Source: Pitt B et al. NEJM 2003;348:1309-1321

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

Eplerenone

3,313 patients with evidence of HF and LVSD (EF <0.40) after a MI randomized to eplerenone (25-50 mg) or placebo for 16 months

Aldosterone inhibition improves survival in patients with post-MI HF and LVSD


Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)


Primary endpoint**0

50

100

%

18.325.9

12.5 15.5

5

All-cause mortality0

10

%Eplerenone

Placebo

2737 patients with NYHA Class II HF symptoms and LVSD (mean LV EF 26%) randomized to eplerenone (25-50 mg) or placebo for a median of 21 months*

Aldosterone inhibition improves survival in patients with mild HF and LVSD

CV=Cardiovascular, EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NYHA=New York Heart Association

*The study was stopped prematurely

Source: Zannad F et al. NEJM 2011;364:11-21

**Composite of CV death or hospitalization for HF

Use of aldosterone blockade in post-MI patients without significant renal dysfunction* or hyperkalemia** is recommended in patients who are already receiving therapeutic doses of an ACE inhibitor and beta-blocker, who have a LV EF <40%, and who have either DM or HF

ACE=Angiotensin converting enzyme, DM=Diabetes mellitus, EF=Ejection fraction, HF=Heart failure,

LV=Left ventricular, MI=Myocardial infarction

I IIa IIb III

Aldosterone Antagonist GuidelinesAldosterone Antagonist Guidelines


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

*Estimated creatinine clearance should be >30 ml/min **Potassium should be <5.0 mEq/L



Digoxin Evidence Digoxin Evidence and Guidelinesand Guidelines

K+ Na+

Na+ K+ Na+ Ca++

Na-Ca ExchangeNa-K ATPase

Myofilaments

Ca++

Contractility

Digoxin

Digoxin:Digoxin:Mechanism of ActionMechanism of Action

Source: Digitalis Investigation Group. NEJM 1997;336:525-533

Digitalis Investigation Group (DIG) Trial6,800 patients with LV systolic dysfunction (EF <45%) randomized to

digitalis (0.25 mg) or placebo for 37 months

Digitalis reduces the rate of hospitalization for heart failure*

*28% relative risk reduction (p<0.001)

Digitalis

Placebo

HR=0.75, P<0.001

Digoxin:Digoxin:Secondary PreventionSecondary Prevention

http://content.nejm.org/content/vol336/issue8/images/large/01f3.jpeg

Digoxin in those with symptomatic HF and LVSD (EF <45%) to reduce hospitalizations for HF*

Digoxin in those with asymptomatic LVSD and normal sinus rhythm

EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic function

*Contraindications include significant sinus or atrioventricular block unless a permanent pacemaker is present

Source: Hunt SA et al. Circulation 2005;112:e154-235

I IIa IIb III

I IIa IIb III

Digoxin GuidelinesDigoxin Guidelines




Implantable Cardioverter DefibrillatorImplantable Cardioverter Defibrillator Evidence and GuidelinesEvidence and Guidelines

Sources:1Moss AJ et al. NEJM 1996;335:1933-1940

2Buxton AE et al. NEJM 1999;341:1882-18903Moss AF et al. NEJM 2002;346:877-883

54%

75%

55%

73%

31%

61%

27 MonthsEF <35%

39 MonthsEF <40%

20 MonthsEF <30%

% m

orta

lity

redu

ctio

n w

ith IC

D

*Primary prevention of sudden cardiac death

Overall deathArrhythmic death

0

20

40

60

80

MADIT1 MUSTT2 MADIT-II3

Implantable Cardioverter Defibrillator:Implantable Cardioverter Defibrillator:Secondary PreventionSecondary Prevention

EF < 30%

EPS

Yes

+

Source: DiMarco JP et al. NEJM 2003;349:1836-1847

EF 31-40%

No

No ICDMedical Rx

EF > 40%

-

At least one month following MI

EF=Ejection fraction, EPS=Electrophysiology study, ICD=Implantable cardioverter defibrillator, Rx=Treatment

Implantable Cardioverter Defibrillator:Implantable Cardioverter Defibrillator:Algorithm in Secondary PreventionAlgorithm in Secondary Prevention

Patients with an ejection fraction of <35% who are at least 40 days post-MI and are in NYHA functional Class II or III

Patients with an ejection fraction of <30% who are at least 40 days post-MI and are in NYHA functional Class I

Patients with nonsustained VT due to prior MI, an ejection fraction of <40%, and inducible sustained VT or VF at EP study

EP=Electrophysiology, MI=Myocardial infarction, NYHA=New York Heart Association, VF=Ventricular fibrillation, VT=Ventricular tachycardia

Epstein AE et al. Circulation 2008;117:e350-408

Implantable CardioverterImplantable CardioverterDefibrillator GuidelinesDefibrillator Guidelines

I IIa IIb III

I IIa IIb III




Room for ImprovementRoom for Improvement

ACTION Registry/Get With The Guidelines (GWTG) Data

NSTEMI

STEMI

Source: ACTION Registry-GWTG DATA: January 1, 2010 – December 31, 2010. Courtesy of NCDR 10/21/2011

0%

20%

40%

60%

80%

100%

ASA Beta Blockers ACE-1 or ARB Statins Clopidogrel

99% 97% 97% 95%88%

83%

94%88% 86%

72%

Utilization of Risk Reducing Utilization of Risk Reducing MedicationsMedicationsat Discharge in Acute Coronary at Discharge in Acute Coronary SyndromesSyndromes

NSTEMI=Non-ST-segment elevation myocardial infarction, STEMI=ST-segment elevation myocardial infarction

Duke Databank for Cardiovascular Disease*

Source: Newby LK et al. Circulation 2006;113:203-212

ASA=Aspirin, ACE-I=Angiotensin converting enzyme inhibitor, BB=Beta-blocker, CAD=Coronary artery disease, CHF=Congestive heart failure, HF=Heart failure

Self-Reported Medications in Patients Self-Reported Medications in Patients with with Coronary Artery Disease Coronary Artery Disease ++ Heart Heart FailureFailure

*n=31,750

NHANES III (Phase 2) 1991-1994

NHANES III (Phase 1) 1988-1991

51%

73%68%

31%

55% 54%

10%

29% 27%% A

du

lts

Awareness

NHANES II 1976-1980

Treatment

Control

NHANES 1999-2000

70%

59%

34%

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

National Health and Nutrition Examination Survey (NHANES)

Hypertension Awareness, Treatment, Hypertension Awareness, Treatment, and Control in the United Statesand Control in the United States

0

20

40

60

80


Source: Gu Q et al. Circulation 2006;113:213-221

ACE=Angiotensin converting enzyme

Antihypertensive Drug UseAntihypertensive Drug Usein the United Statesin the United States

Source: Jackevicius CA et al. JAMA 2002;288:462-467

Adh

e re n

ce R

a te

(%)

0 3 6 9 12 15 18 21 24

Months

0

20

40

60

80

100

Acute Coronary Syndrome

Coronary Artery DiseasePrimary Prevention

n=22379

n=85020n=36106

HMG-CoA Reductase Inhibitor:HMG-CoA Reductase Inhibitor:Adherence to TherapyAdherence to Therapy

National Health and Nutrition Examination Survey (NHANES)*

Keevil JG et al. Circulation 2007;115:1363-1370

*Based on 7,399 subjects in NHANES from 1999-2002

Cholesterol Treatment GapCholesterol Treatment Gapin the United Statesin the United States

Saydah S et al. JAMA 2004;291:335-342

(%)


BP=Blood pressure, DM=Diabetes mellitus, HbA1C=Glycosylated hemoglobin, TC=Total cholesterol

0102030405060708090

100

HbA1c<7% BP <130/80mm Hg

TC <200mg/dL

Good Control of all 3

NHANES III NHANES IV

Achievement of Risk Factor GoalsAchievement of Risk Factor GoalsAmong Diabetics in the United StatesAmong Diabetics in the United States

ACTION Registry/Get With The Guidelines (GWTG) Data

NSTEMI

STEMI

ACTION Registry-GWTG DATA: January 1, 2010 – December 31, 2010. Courtesy of NCDR 10/21/2011

0%

20%

40%

60%

80%

100%

Exercise Counseling

Dietary Modification

Cardiac Rehab Referral

Smoking Cessation

Utilization of Risk Reducing Utilization of Risk Reducing InterventionsInterventionsat Discharge in Acute Coronary at Discharge in Acute Coronary SyndromesSyndromes

NSTEMI=Non-ST-segment elevation myocardial infarction, STEMI=ST-segment elevation myocardial infarction



Quality ImprovementQuality ImprovementInitiativesInitiatives

Hospital based performance improvement systems

In-hospital initiation of CV protective therapies

Pay for performance/financial incentives

Nurse or pharmacist managed outpatient CV prevention programs

Preventive cardiology and cardiac rehabilitation centers

Virtual prevention clinics using electronic medical record systems

Combination of CV protective medications

CV=Cardiovascular

Strategies for Initiating and Strategies for Initiating and Optimizing Optimizing Cardiovascular TherapiesCardiovascular Therapies

Get With the Guidelines-Coronary Artery Disease (GWTG-CAD)

Lewis WR et al. Circ Cardiovasc Qual Outcomes 2009;2:633-641

Perc

ent

adhere

nce

Composite performance measure adherence by age and gender

Quarters of participation

Utilization of Risk Reducing TherapiesUtilization of Risk Reducing Therapiesin Coronary Artery Diseasein Coronary Artery Disease

0

5

10

15

20

25

30

35

40

45

In-hospital Mortality

Mo

rta

lity

(%)

Baseline

Post-GAP

P=0.017

P=0.001

P=0.004

Guidelines Applied in Practice (GAP) Initiative

Eagle KA et al. JACC 2005;46:1242-1248

30-day Mortality

1-yrMortality

MI=Myocardial infarction

Utilization of Risk Reducing TherapiesUtilization of Risk Reducing TherapiesAfter Acute Myocardial InfarctionAfter Acute Myocardial Infarction

Fox KAA et al. JAMA 2007;297:1892-1900

Global Registry of Acute Coronary Events (GRACE)

Utilization of Risk Reducing TherapiesUtilization of Risk Reducing TherapiesAfter ST-Segment Elevation Myocardial After ST-Segment Elevation Myocardial InfarctionInfarctionRegistry of 4,608 patients with a ST-segment elevation myocardial

infarction

% P

atie

nts

Fonarow GC et al. Am J Cardiol 2001;87:819-822

Event

Rate

, %

Recurrent MI Heart Failure Hospitalization Total Mortality

Pre-CHAMP*

Post-CHAMP*

7.8

4.7

14.8

7.0

3.1†

2.6

7.6†

3.3†

†P<0.05

Cardiac Hospital Atherosclerosis Management Program (CHAMP)

ACS=Acute coronary syndrome, MI=Myocardial infarction

0

5

10

15

Utilization of Risk Reducing TherapiesUtilization of Risk Reducing TherapiesAfter Non-ST-Segment Elevation ACSAfter Non-ST-Segment Elevation ACS

*1 year outcomes

8

7

6

5

4

3

2

1

01 2 3 4

In-H

osp

ital M

ort

alit

y, %

Hospital Composite GuidelineAdherence Quartiles

NSTE-ACS 8

7

6

5

4

3

2

1

01 2 3 4

In-H

osp

ital M

ort

alit

y, %

Hospital Composite GuidelineAdherence Quartiles

NSTE-MI

Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the

ACC/AHA Guidelines (CRUSADE) Registry

Peterson ED et al. JAMA 2006;295:1912-1920

NSTE-ACS=Non-ST-segment elevation acute coronary syndrome, NSTE-MI=Non-ST segment elevation myocardial infarction


Global Registry of Acute Coronary Events (GRACE)Registry of 8,375 patients with a non-ST-segment elevation ACS

Fox KAA et al. JAMA 2007;297:1892-1900


ACS=Acute coronary syndrome

Federal Study of Adherence to Medications in the Elderly (FAME)

*Includes standardized medication education, regular follow-up by pharmacists, and medications dispensed in time-specific blister packs

Lee JK et al. JAMA 2006;296:2563-2571

200 patients with CV risk factors randomized to pharmacy intervention* or usual care for 6 months

An intervention program significantly improves adherence

Pharmacy Intervention to ImprovePharmacy Intervention to ImproveUtilization of Risk Reducing TherapiesUtilization of Risk Reducing Therapies

CV=Cardiovascular

the evidence for current cardiovascular disease prevention guidelines: other cardiovascular...

Documents

levels of evidence

evidence levels

history of diabetes

years of age

diabetes care

clinical trials

cardiovascular therapies

repeat vaccination