Transcript Slide 1

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 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
Vaccination Evidence
and Guidelines
Influenza Vaccination:
Primary Prevention
286,383 community-dwelling members aged >65 years of 3 large managedcare organizations evaluated for 1-2 yrs
Adverse Outcome
Vaccinated
Subjects
(N=77,738)
Unvaccinated
Adjusted
Subjects
Odds Ratio
(N=62,317)
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
P value
Influenza vaccination reduces the rate of adverse CV events
CV=Cardiovascular
Source: Nichol KL et al. NEJM 2003;348:1322-1332
ADA Immunization Recommendations
for Patients with Diabetes Mellitus
Primary Prevention
• 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=American Diabetes Association
Source: American Diabetes Association. Diabetes Care 2010;33:S11-61
Influenza Vaccination Guidelines
I IIa IIb III
Secondary Prevention
Patients with cardiovascular disease should have an
annual influenza vaccination
Source: Smith Jr SC et al. JACC 2011;58:2432-2446
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Ejection Fraction Evidence
and Guidelines
Relationship Between Ejection Fraction
Post Myocardial Infarction and Mortality
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
LV EF=Left ventricular ejection fraction, MI=Myocardial infarction, RNA=Radionuclide
angiography, SPECT=Single photon emission computed tomography
Source: Burns RJ et al. JACC 2002;39:30-36
Ejection Fraction Guidelines
Secondary Prevention
I IIa IIb III
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‡
NSTE-ACS=Non-ST-segment elevation acute coronary syndrome,
STEMI=ST-segment elevation myocardial infarction
Sources:
EM et al. JACC 2004;44:671-719
‡Anderson JL et al. JACC 2007;50:652-726
†Antman
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Aldosterone Antagonist Evidence
and Guidelines
Aldosterone Antagonist:
Mechanisms of Action
Aldosterone
Sodium and
Water
Retention
Edema
Potassium and
Magnesium
Excretion
Arrhythmias
Collagen
deposition
Myocardial and
Vascular Fibrosis
Aldosterone Antagonist:
Secondary Prevention
Randomized Aldactone Evaluation Study (RALES)
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
Survival (%)
1.00
.90
.80
.70
Spironolactone
.60
.50
Placebo
RR = 0.70, P<0.001
0
0
3
6
9
12 15 18 21 24 27 30 33
36
Months
Aldosterone inhibition improves survival in patients with advanced
heart failure
EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular
systolic dysfunction, NYHA=New York Heart Association
Source: Pitt B et al. NEJM 1999;341:709-717
Aldosterone Antagonist:
Secondary Prevention
Eplerenone Post-Acute Myocardial Infarction Heart Failure
Efficacy and Survival Study (EPHESUS)
All Cause Mortality (%)
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
25
Placebo
20
Eplerenone
15
10
5
RR = 0.85, P=0.008
0
0
6
12
18
Month
24
30
36
Aldosterone inhibition improves survival in patients with post-MI HF
and LVSD
EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction,
MI=Myocardial infarction, HF=Heart failure
Source: Pitt B et al. NEJM 2003;348:1309-1321
Aldosterone Antagonist:
Secondary Prevention
Eplerenone in Mild Patients Hospitalization and Survival Study
in Heart Failure (EMPHASIS-HF)
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*
10
100
Eplerenone
% 50
% 5
18.3
Placebo
25.9
0
Primary endpoint**
12.5 15.5
0
All-cause mortality
Aldosterone inhibition improves survival in patients with mild HF and LVSD
*The study was stopped prematurely
**Composite of CV death or hospitalization for HF
CV=Cardiovascular, EF=Ejection fraction, HF=Heart failure, LVSD=Left
ventricular systolic dysfunction, NYHA=New York Heart Association
Source: Zannad F et al. NEJM 2011;364:11-21
Aldosterone Antagonist Guidelines
Secondary Prevention
I IIa IIb III
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
*Estimated creatinine clearance should be >30 ml/min
**Potassium should be <5.0 mEq/L
ACE=Angiotensin converting enzyme, DM=Diabetes
mellitus, EF=Ejection fraction, HF=Heart failure,
LV=Left ventricular, MI=Myocardial infarction
Source: Smith SC Jr. et al. JACC 2011;58:2432-2446
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Digoxin Evidence
and Guidelines
Digoxin:
Mechanism of Action
Digoxin
Na-K ATPase
Na+ K+
Na-Ca Exchange
Na+
Ca++
Myofilaments
K+
Ca++
Na+
Contractility
Digoxin:
Secondary Prevention
Digitalis Investigation Group (DIG) Trial
6,800 patients with LV systolic dysfunction (EF <45%) randomized to digitalis
(0.25 mg) or placebo for 37 months
Placebo
Digitalis
HR=0.75, P<0.001
Digitalis reduces the rate of hospitalization for heart failure*
*28% relative risk reduction (p<0.001)
Source: Digitalis Investigation Group. NEJM 1997;336:525-533
Digoxin Guidelines
I IIa IIb III
Secondary Prevention
Digoxin in those with symptomatic HF and LVSD (EF
<45%) to reduce hospitalizations for HF*
I IIa IIb III
Digoxin in those with asymptomatic LVSD and normal
sinus rhythm
*Contraindications include significant sinus or atrioventricular
block unless a permanent pacemaker is present
EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic function
Source: Hunt SA et al. Circulation 2005;112:e154-235
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Implantable Cardioverter Defibrillator
Evidence and Guidelines
% mortality reduction with ICD
Implantable Cardioverter Defibrillator:
Secondary Prevention
80
75%
73%
Overall death
Arrhythmic death
61%
60
54%
55%
40
31%
20
0
MADIT1
MUSTT2
MADIT-II3
27 Months
EF <35%
39 Months
EF <40%
20 Months
EF <30%
*Primary prevention of sudden cardiac death
Sources:
AJ et al. NEJM 1996;335:1933-1940
2Buxton AE et al. NEJM 1999;341:1882-1890
3Moss AF et al. NEJM 2002;346:877-883
1Moss
Implantable Cardioverter Defibrillator:
Algorithm in Secondary Prevention
At least one month following MI
EF < 30%
EF > 40%
EF 31-40%
Additional Marker of
Electrical Instability?
Yes
+
EPS
No
-
No ICD
Medical Rx
EF=Ejection fraction, EPS=Electrophysiology study,
ICD=Implantable cardioverter defibrillator, Rx=Treatment
Source: DiMarco JP et al. NEJM 2003;349:1836-1847
Implantable Cardioverter
Defibrillator Guidelines
Secondary Prevention
I IIa IIb III
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
I IIa IIb III
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
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Room for Improvement
Utilization of Risk Reducing Medications
at Discharge in Acute Coronary Syndromes
ACTION Registry/Get With The Guidelines (GWTG) Data
100%
99% 97%
97% 95%
94%
88%
83%
88%
86%
80%
72%
60%
NSTEMI
STEMI
40%
20%
0%
ASA
Beta Blockers ACE-1 or ARB
Statins
Clopidogrel
NSTEMI=Non-ST-segment elevation myocardial infarction,
STEMI=ST-segment elevation myocardial infarction
Source: ACTION Registry-GWTG DATA: January 1, 2010 –
December 31, 2010. Courtesy of NCDR 10/21/2011
Self-Reported Medications in Patients with
Coronary Artery Disease + Heart Failure
Duke Databank for Cardiovascular Disease*
*n=31,750
ASA=Aspirin, ACE-I=Angiotensin converting enzyme inhibitor, BB=Beta-blocker,
CAD=Coronary artery disease, CHF=Congestive heart failure, HF=Heart failure
Source: Newby LK et al. Circulation 2006;113:203-212
Hypertension Awareness, Treatment,
and Control in the United States
National Health and Nutrition Examination Survey (NHANES)
80
73%
% Adults
60
40
51%
31%
55%
68%
70% Awareness
59%
Treatment
54%
34%
Control
29%
27%
NHANES II
NHANES III
NHANES III
NHANES
1976-1980
(Phase 1)
1988-1991
(Phase 2)
1991-1994
1999-2000
20
10%
0
Source: Chobanian AV et al. JAMA 2003;289:2560-2572
Antihypertensive Drug Use
in the United States
National Health and Nutrition Examination Survey (NHANES)
ACE=Angiotensin converting enzyme
Source: Gu Q et al. Circulation 2006;113:213-221
HMG-CoA Reductase Inhibitor:
Adherence to Therapy
100
Acute Coronary Syndrome
n=22379
80
60
Primary Prevention
Coronary Artery Disease
n=85020
40
n=36106
20
0
0
3
6
9
12
15
18
21
24
Months
Source: Jackevicius CA et al. JAMA 2002;288:462-467
Cholesterol Treatment Gap
in the United States
National Health and Nutrition Examination Survey (NHANES)*
*Based on 7,399 subjects in NHANES from 1999-2002
Keevil JG et al. Circulation 2007;115:1363-1370
Achievement of Risk Factor Goals
Among Diabetics in the United States
(%)
National Health and Nutrition Examination Survey (NHANES)
100
90
80
70
60
50
40
30
20
10
0
NHANES III
HbA1c<7%
BP <130/80
mm Hg
NHANES IV
TC <200
mg/dL
Good Control of
all 3
BP=Blood pressure, DM=Diabetes mellitus,
HbA1C=Glycosylated hemoglobin, TC=Total cholesterol
Saydah S et al. JAMA 2004;291:335-342
Utilization of Risk Reducing Interventions
at Discharge in Acute Coronary Syndromes
ACTION Registry/Get With The Guidelines (GWTG) Data
100%
80%
60%
NSTEMI
STEMI
40%
20%
0%
Exercise
Counseling
Dietary
Cardiac Rehab
Modification
Referral
Smoking
Cessation
NSTEMI=Non-ST-segment elevation myocardial infarction,
STEMI=ST-segment elevation myocardial infarction
ACTION Registry-GWTG DATA: January 1, 2010 –
December 31, 2010. Courtesy of NCDR 10/21/2011
Evidence for Current Cardiovascular Disease
Prevention Guidelines
Quality Improvement
Initiatives
Strategies for Initiating and Optimizing
Cardiovascular Therapies
 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
Utilization of Risk Reducing Therapies
in Coronary Artery Disease
Get With the Guidelines-Coronary Artery Disease (GWTG-CAD)
Composite performance measure adherence by age and gender
Quarters of participation
Lewis WR et al. Circ Cardiovasc Qual Outcomes 2009;2:633-641
Utilization of Risk Reducing Therapies
After Acute Myocardial Infarction
Guidelines Applied in Practice (GAP) Initiative
45
40
Mortality (%)
35
P=0.004
Baseline
Post-GAP
30
P=0.001
25
20
15
P=0.017
10
5
0
In-hospital
Mortality
30-day
Mortality
1-yr
Mortality
MI=Myocardial infarction
Eagle KA et al. JACC 2005;46:1242-1248
Utilization of Risk Reducing Therapies
After ST-Segment Elevation Myocardial Infarction
Global Registry of Acute Coronary Events (GRACE)
% Patients
Registry of 4,608 patients with a ST-segment elevation myocardial infarction
Fox KAA et al. JAMA 2007;297:1892-1900
Utilization of Risk Reducing Therapies
After Non-ST-Segment Elevation ACS
Cardiac Hospital Atherosclerosis Management Program (CHAMP)
14.8
Pre-CHAMP*
15
Post-CHAMP*
10
7.6†
7.8
7.0
4.7
5
3.1†
3.3†
2.6
0
Recurrent MI
Heart Failure
Hospitalization
Total Mortality
*1 year outcomes
†P<0.05
ACS=Acute coronary syndrome, MI=Myocardial infarction
Fonarow GC et al. Am J Cardiol 2001;87:819-822
Utilization of Risk Reducing Therapies
After Non-ST-Segment Elevation ACS
Can Rapid Risk Stratification of Unstable Angina Patients
Suppress Adverse Outcomes with Early Implementation of the
ACC/AHA Guidelines (CRUSADE) Registry
NSTE-ACS
7
6
5
4
3
2
1
0
8
In-Hospital Mortality, %
In-Hospital Mortality, %
8
1
2
3
4
Hospital Composite Guideline
Adherence Quartiles
NSTE-MI
7
6
5
4
3
2
1
0
1
2
3
4
Hospital Composite Guideline
Adherence Quartiles
NSTE-ACS=Non-ST-segment elevation acute coronary syndrome,
NSTE-MI=Non-ST segment elevation myocardial infarction
Peterson ED et al. JAMA 2006;295:1912-1920
Utilization of Risk Reducing Therapies
After Non-ST-Segment Elevation ACS
Global Registry of Acute Coronary Events (GRACE)
Registry of 8,375 patients with a non-ST-segment elevation ACS
ACS=Acute coronary syndrome
Fox KAA et al. JAMA 2007;297:1892-1900
Pharmacy Intervention to Improve
Utilization of Risk Reducing Therapies
Federal Study of Adherence to Medications in the Elderly (FAME)
200 patients with CV risk factors randomized to pharmacy intervention* or
usual care for 6 months
An intervention program significantly improves adherence
*Includes standardized medication education, regular follow-up by
pharmacists, and medications dispensed in time-specific blister packs
CV=Cardiovascular
Lee JK et al. JAMA 2006;296:2563-2571