1 Other Risk Reducing Therapies, Guidelines, and Areas for Improvement Andrew P. DeFilippis, Ty J....

1

Other Risk Reducing Therapies, Other Risk Reducing Therapies, Guidelines, and Areas for Guidelines, and Areas for

ImprovementImprovement

Andrew P. DeFilippis, Ty J. Gluckman, James Mudd, Catherine Campbell, Gregg Fonarow

& Roger S. Blumenthal

2

Influenza Evidence and GuidelinesInfluenza Evidence and Guidelines

3Nichol KL et al. NEJM 2003;348:1322-32

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

Influenza Vaccination: Primary PreventionInfluenza Vaccination: Primary Prevention

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

Influenza vaccination reduces adverse CV events

4

Patients with cardiovascular disease should receive the influenza vaccination annually

Influenza VaccinationInfluenza Vaccination

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

5

Ejection fraction Evidence and Ejection fraction Evidence and

GuidelinesGuidelines

6

80706050403020

54-60 >60

50

40

30

20

10

0

<30

31-35

36-45

46-53

Car

diac

Mor

talit

y %

Brodie B et al. Am J Cardiol 1992;69:1113-9

Relationship Between EF* and MortalityRelationship Between EF* and Mortality

Ejection Fraction (%)

*Post myocardial infarction

EF=Ejection fraction

7

Ejection Fraction GuidelinesEjection Fraction Guidelines


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*

*Includes use of an aldosterone antagonist, digitalis, and/or an implantable cardioverter defibrillator

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

Secondary Prevention

8

Aldosterone Antagonist Evidence and Aldosterone Antagonist Evidence and GuidelinesGuidelines

9

Aldosterone Antagonist: Mechanism of ActionAldosterone Antagonist: Mechanism of Action

Aldosterone

Sodium and Water

Retention

Edema

Potassium and Magnesium Excretion

Arrhythmias

Collagen deposition

Myocardial and Vascular Fibrosis

10Pitt B et al. NEJM 1999;341:709-717

RR = 0.70, P<0.001

Months

Sur

viva

l (%

)

3633302724211815129630

1.00

.90

.80

.70

.60

.50

0

Aldosterone Antagonist: Secondary PreventionAldosterone Antagonist: Secondary Prevention

Randomized Aldactone Evaluation Study (RALES)

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

SpironolactonePlacebo

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 reduces death in patients with advanced heart failure

11

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

Aldosterone Antagonist: Secondary PreventionAldosterone Antagonist: Secondary Prevention

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

EplerenonePlacebo

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

Pitt B et al. NEJM 2003;348:1309-21

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

12

Aldosterone Antagonist: GuidelinesAldosterone Antagonist: Guidelines


Aldosterone antagonist in UA/NSTEMI patients already receiving and ACE-I with LVSD (EF <0.40) and either symptomatic HF or DM

Aldosterone antagonist in those with LVSD (EF<0.35) and recent or current NYHA class IV HF symptoms*


ACE-I=Angiotensin converting enzyme inhibitor, DM=Diabetes mellitus, EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, NYHA=New York Heart Association

*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)


13

Digitalis Evidence and GuidelinesDigitalis Evidence and Guidelines

14

Digitalis: Mechanism of ActionDigitalis: Mechanism of Action

K+ Na+

Na+ K+ Na+ Ca++

Na-Ca ExchangeNa-K ATPase

Myofilaments

Ca++

Contractility

Digitalis

15Digitalis Investigation Group. NEJM 1997;336:525-33

Digitalis: Secondary PreventionDigitalis: Secondary Prevention

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 hospitalization for heart failure*

*28% relative risk reduction (p<0.001)

Digitalis

Placebo

HR=0.75, P<0.001

16

Digitalis: RecommendationsDigitalis: Recommendations

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

Digitalis 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



17

ICD Evidence and GuidelinesICD Evidence and Guidelines

18

1 Moss AJ et al. NEJM 1996;335:1933-19402 Buxton AE et al. NEJM 1999;341:1882-18903 Moss AF et al. NEJM 2002;346:877-883

0

20

40

60

80

MADIT MUSTT MADIT-II1 2 3

54%

75%

55%

73%

31%

61%

27 Months 39 Months 20 Months

% m

orta

lity

redu

ctio

n w

ith I

CD

ICD: Secondary Prevention*ICD: Secondary Prevention*

*Primary prevention of sudden cardiac death

Overall death

Arrhythmic death

EF <35% EF <40% EF <30%

19

ICD Algorithm

EF < 30%

EPS

Yes

+

DiMarco JP et al. NEJM 2003;349:1836-47

EF 31-40%

No

No ICDMedical Rx

EF > 40%

-

Additional Marker of Electrical Instability?

At least one month following MI

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

20

Patients with an ejection fraction of <30% at least 1 month after a MI and 3 months after CABG

Patients with nonsustained VT, CAD, prior MI, LV dysfunction, and inducible sustained VT of VF at electrophysiology study

ICD GuidelinesICD Guidelines



CABG=Coronary artery bypass graft surgery, CAD=Coronary artery disease, LV=Left ventricular, MI=Myocardial infarction, VF=Ventricular fibrillation, VT=Ventricular tachycardia

21

Room for ImprovementRoom for Improvement

22

77

60

26

36

12

55

32 35

26 24

48

30 3227

22

0

20

40

60

80

Aspirin Beta-Blocker

ACE-I Lipid-LoweringTreatment

Digoxin

Discharge Medications

Pat

ient

s T

reat

ed (

%)

HF Absent

HF on Presentation

HF After Presentation

Discharge Medications in Patients Post-MI Discharge Medications in Patients Post-MI ++ HF HF

National Registry of Myocardial Infarction (NRMI)

Spencer FA et al. Circulation 2002;105:2605-2610

ACE-I=Angiotensin converting enzyme inhibtor, HF=Heart failure, MI=Myocardial infarction

23

Self-Reported Medications in Patients with CAD Self-Reported Medications in Patients with CAD ++ HF HF

Duke Databank for Cardiovascular Disease (n=31,750)

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

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

24

NHANES III (Phase 2) 1991-1994

NHANES III (Phase 1) 1988-1991

0

10

20

30

40

50

60

70

80

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%

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

U.S. Hypertension Awareness, Treatment, and ControlU.S. Hypertension Awareness, Treatment, and Control

National Health and Nutrition Examination Survey (NHANES)

25

Antihypertensive Drug Use among U.S. AdultsAntihypertensive Drug Use among U.S. Adults


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

ACE=Angiotensin converting enzyme

26

% n

ot a

t L

DL-

C t

arge

t

2 RF (LDL <130 mg/dl) CHD (LDL <100 mg/dl)

Risk profile

63

8283

55

0

20

40

60

80

100 NHANES IIIL-TAP

National Center for Health Statistics. National Health and Nutrition Examination Survey (III); 1994. (Data collected 1991-1994)Pearson TA et al. Arch Intern Med 2000;160:459-467

Percent of U.S. Adults Achieving LDL-C GoalPercent of U.S. Adults Achieving LDL-C Goal

National Health and Nutrition Examination Survey (NHANES) and Lipid Treatment Assessment Project (L-TAP)

27

NHANES 1994, IMS 2003, Ingenix Treatment Gap Data 2003

0

5

10

15

20

25

Moderate RiskPrimary Prevention

11-18 million

24-26 million

High RiskSecondary Prevention/CHD Risk Equivalents

Rx

Elig

ible

Am

eric

ans

(Mill

ions

)

Rx treated

3-5 million

9-11 million

Gap

Gap

Recommended for drug therapy

U.S. Treatment Gap in Lipid LoweringU.S. Treatment Gap in Lipid Lowering


28

0 3 6 9 12 15 18 21 24

Months

0

20

40

60

80

100% Adherent with Statins

Acute Coronary Syndrome

Coronary Artery Disease

Primary Prevention

n=22379

n=85020 n=36106

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

Adherence Rates to HMG-coA Reductase InhibitorsAdherence Rates to HMG-coA Reductase InhibitorsA

dhe r

e nce

Ra t

e (%

)

29Saydah S et al. JAMA 2004;291:335-342

(%)

HbA1c <7% BP <130/80 mm Hg

TC <200 mg/dL

Good Control of all 3

U.S. Adults with DM Achieving Risk Factor GoalsU.S. Adults with DM Achieving Risk Factor Goals


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

30

**LVEF <40%, CHF, DM, HTN#Known hyperlipidemia, TC, LDL

Discharge Medications Following a NSTE-ACS*Discharge Medications Following a NSTE-ACS*

CRUSADE Initiative

Mehta RH et al. Arch Intern Med 2006;166:2027-2034

0

10

20

30

40

50

60

70

80

90

100

Me

dic

atio

n U

se

, %

Antiplatelet B-Blockers Clopidogrel Lipid-Lowering

ACE-I

Q1Q4Q8Q11

31

Quality Improvement InitiativesQuality Improvement Initiatives

32

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

Strategies for Initiating and Optimizing CV Therapies Strategies for Initiating and Optimizing CV Therapies

CV=Cardiovascular

33

93

79

64 67

57

95

83

6570 70

97

87

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

*

*** * *

*

LaBresh KA et al. Circulation 2003;108:IV-722

**

*

Utilization of Risk Reducing Therapies in CAD Utilization of Risk Reducing Therapies in CAD

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

123 U.S. Hospitals, n=27,825

34

Improved Utilization of Risk Reducing TherapiesImproved Utilization of Risk Reducing Therapies

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

35

0

5

10

15

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

Eve

nt R

a te

, %

Recurrent MI Heart Failure Hospitalization Total Mortality

Pre-CHAMPPost-CHAMP

8

4.7

15

7.0

3*2.6

7.6*

3*

*P<0.05

1-Year Post-Intervention Outcomes After NSTE-ACS1-Year Post-Intervention Outcomes After NSTE-ACS

CHAMP Study

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

36

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

Post Intervention Mortality After Acute MI Post Intervention Mortality After Acute MI

Guidelines Applied in Practice (GAP) Initiative

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

30-day Mortality

1-yrMortality

MI=Myocardial infarction

37

8

7

6

5

4

3

2

1

01 2 3 4

In-H

ospi

tal M

orta

lity,

%

Hospital Composite GuidelineAdherence Quartiles

NSTE-ACS 8

7

6

5

4

3

2

1

01 2 3 4

In-H

ospi

tal M

orta

lity,

%

Hospital Composite GuidelineAdherence Quartiles

NSTE-MI

CRUSADE = Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines.

In-Hospital Post-Intervention Mortality OutcomesIn-Hospital Post-Intervention Mortality Outcomes

CRUSADE Initiative

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

1 Other Risk Reducing Therapies, Guidelines, and Areas for Improvement Andrew P. DeFilippis, Ty J....

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