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1
Cardiovascular & Renal Drugs Advisory Committee
Meeting
Presentation
2
Bayer HealthCare’s Citizen Petition for Expanded Aspirin Professional Labeling to Include Moderate Risk Patients
Erica Peitler, RPhSr. VP Global Strategic InitiativesBayer HealthCare LLCMorristown, New Jersey
3
Key Points
• Consensus that ASA prevents MI
4
Key Points
• Consensus that ASA prevents MI
• ASA is cost effective, yet underutilized
5
Key Points
• Consensus that ASA prevents MI
• ASA is cost effective, yet underutilized
• Guidelines support ASA use in moderate risk
6
Key Points
• Consensus that ASA prevents MI
• ASA is cost effective, yet underutilized
• Guidelines support ASA use in moderate risk
• Expanded labeling for ASA can have significant public health impact
7
Key Points
• Consensus that ASA prevents MI
• ASA is cost effective, yet underutilized
• Guidelines support ASA use in moderate risk
• Expanded labeling for ASA can have significant public health impact
• Request FDA recognition of global risk assessment rather than event-based risk
8
Key Points
• Consensus that ASA prevents MI
• ASA is cost effective, yet underutilized
• Guidelines support ASA use in moderate risk
• Expanded labeling for ASA can have significant public health impact
• Request FDA recognition of global risk assessment rather than event-based risk
• Totality of evidence advances our understanding of appropriate patient selection
9
Key Points
• Consensus that ASA prevents MI
• ASA is cost effective, yet underutilized
• Guidelines support ASA use in moderate risk
• Expanded labeling for ASA can have significant public health impact
• Request FDA recognition of global risk assessment rather than event-based risk
• Totality of evidence advances our understanding of appropriate patient selection
• Bayer is committed to working with the FDA and the health care provider community to reduce MI burden
10
Expert Participants
• Investigators J. Michael Gaziano, MD
Tobias Kurth, MD, ScDNancy R. Cook, ScD
Physicians’ Health Study Colin Baigent, BMBCh, MSc
British Doctors’ Study Thomas W. Meade, DM, FRS
Thrombosis Prevention Trial Gianni Tognoni, MD
Primary Prevention Project Alberto Zanchetti, MD
Hypertension Optimal Treatment Trial
• Guidelines Michael P. Pignone, MD, MPH (USPSTF) Thomas Pearson, MD, MPH, PhD (AHA) John A. Colwell, MD, PhD (ADA)
• Cardiology/Epidemiology Stephen Kimmel, MD, MSCE Thomas Pearson, MD, MPH, PhD Randall Stafford, MD, PhD
• Cardiologists C. Noel Bairey Merz, MD Charles L. Curry, MD Eric Topol, MD
• Gastrointestinal Safety David Y. Graham, MD Loren Laine, MD James Lewis, MD
• Neurology Tobias Kurth, MD, ScD
• Labeling Steve Hellebusch
Hellebusch Research
11
Agenda
• Rationale for Expanded Aspirin Labeling Thomas Pearson, MD, MPH, PhD
• Safety and Efficacy of Aspirin in Moderate Risk Patients Colin Baigent, MD
• Appropriate Aspirin Use in Women C. Noel Bairey Merz, MD
• Aspirin Utilization: Importance of Labeling Alignment with Medical Practice Randall Stafford, MD, PhD
• Clinical Considerations Eric Topol, MD
12
Rationale for Expanded Aspirin Professional Labeling to Include Moderate Risk Patients
Thomas A. Pearson, MD, MPH, PhDAlbert D. Kaiser Professor and Chair of Community Preventive MedicineSenior Associate Dean for Clinical ResearchUniversity of Rochester School of MedicineRochester, New York
13
Rationale for Expanded Professional ASA Labeling
To Include Patients at “Moderate Risk”
• Proposal Adopt global risk labeling for ASA patient selection Include patients with 10 year risk of CHD that exceeds 10%
where benefits outweigh the risks
• Rationale Coronary heart disease continues to be a major public
health problem Many patients are at sufficient risk of CHD to warrant ASA
treatment Global CHD risk is the appropriate determinant of the type
and intensity of intervention Professional labeling can define Moderate Risk and High
Risk populations where the benefits of treatment outweigh the risks
There is substantial underutilization of ASA in high/moderate risk patients
14
Coronary Heart Disease Overview
• Leading cause of morbidity and mortality in the U.S.
• Despite previous marked reduction in mortality, recent evidence suggests no reduction in MI incidence
• Rising prevalence of CHD carries huge implications to direct and indirect costs
• The first presentation of CHD may be disabling or fatal 20 % of CHD presents as sudden death CHF is one of the only diseases with morbidity, mortality,
incidence and prevalence which has increased annually for the past 25 years
15
Trends in Incidence of MI from 1970-1994 inOlmstead County, MN
50
100
150
200
250
300
350
400
450
79' 80' 81' 82' 83' 84' 85' 86' 87' 88' 89' 90 91' 92' 93' 94'
Men Women
Roger VL et al. Arch Intern Med. 2002;136:341-348.
16
U.S. Heart Disease Prevalence is Projected to Double In the Next Half Century
0
5
10
15
20
25
30
1970 1980 1990 2000 2010 2020 2030 2040 2050
Number of Patients (Millions)
Sources: ACC/AMA Guidelines 2001, NHLBI Chartbook 2000and Adapted from Foot et al (JACC 2000)
12
25
17
Rationale for Primary Prevention
• Largely a preventable disease for which simple, and inexpensive options (including ASA) exist
• Use of safe and effective preventive interventions in this population will have significant public health impact
• Aspirin is the most cost-effective pharmacologic option in CHD prevention
• Patients at moderate to high risk can be effectively identified using clinical judgment and risk assessment tools
18
Guidelines for Risk Assessment
• AHA (2002) and USPSTF (2002) have adopted clinical guidelines encouraging CHD risk assessment and, in patients at Moderate or High Risk, intervention with aspirin Adults 40 years should have an absolute coronary risk
calculated (AHA guidelines) Guidelines for management are based on absolute risk
Serum lipids (NCEP - ATP III) Aspirin (USPSTF, AHA)
Circulation 2002;106:388-391
19
Global Risk Assessment (40 years +)
• Every five years; or more often, especially if 2+ risk factors
• Uses Framingham risk equations
• Uses age, sex, smoking status, systolic BP, total cholesterol, HDL cholesterol
• Diabetes is a CHD risk equivalent
• Calculates 10 year risk of MI or CHD death
• Risk calculator available on NCEP or AHA websites, palm-held devices, color-coded tables, scoring sheets
20
What is This Patient’s Global Risk?
Risk Factor Scenario
Sex Male
Age 52
Smoking Yes
SBP (mmHg) 148
Total Cholesterol (mg/dL) 220
HDL Cholesterol (mg/dL) 38
10 Year Risk of CHD 30%
21
Global Risk Labeling Benefits
• Benefits of Risk Assessment-Based Labeling Providers
Tailor individual treatment decisions based on risk (intervention and intensity)
Choose cost effective therapies Patients
Actively involve patient in risk intervention Motivate to comply with non-pharmacologic and
pharmacologic therapies
22
Aspirin and MI Prevention
• Large database supports safety and efficacy of aspirin in secondary prevention of cardiovascular disease
• AHA/ACC secondary prevention guidelines recommend ASA in patients with established cardiovascular disease
• Current FDA approval to reduce risk of MI in patients with history of MI, stroke, angina, PTCA/CABG procedures (risk 20%)
• ADA guidelines (1997) recommend use of aspirin for primary prevention of heart disease in diabetics
23
Primary Prevention: Individual Studies
• Robust and clinically informative database 5 trials involving over 55,000 subjects
• High compliance and follow-up
• Diverse patient populations Range of baseline global risks Geographical diversity
• Number of doses, formulations, and primary endpoints
24
Primary Prevention: Individual Study Findings
• Five studies provide clinically meaningful data for efficacy and safety Two trials stopped early because of evidence for
aspirin effectiveness (PHS, PPP) Findings consistent in four of five studies
Findings have been used in meta-analysis to more precisely estimate benefit and risk
• Findings consistent with secondary prevention trials
• AHA (2002) and USPSTF (2002) encourage use in moderate risk patients based on these findings
25
Benefit Risk Evaluation
• Estimates of benefits and harm of aspirin given for 5 years to 1,000 persons with various levels of baseline risk for coronary heart disease*
*U.S. Preventive Services Task Force. Ann Intern Med 2002;136:157-160 (modified).
Benefits and Harms Baseline Risk for CHD over 10 Years
2% 6% 10%
Total mortality No effect No effect No effect
Coronary heart disease 1-4 avoided 4-12 avoided 6-20 avoided events, n
Hemorrhagic strokes, n 0-2 caused 0-2 caused 0-2 caused
Major gastrointestinal 2-4 caused 2-4 caused 2-4 caused bleeding events, n
26
Coronary Heart Disease Risk Continuum
# o
f M
Is P
reve
nte
d(P
er 1
000
pat
ient
s tr
eate
d fo
r 10
ye
ars)
Risk of MI or CHD Death (10 year)
Low Risk Moderate Risk High Risk
10% 20%
• Three risk groups can be identified with a global risk score: low, moderate, high
27
Coronary Heart Disease Risk Continuum
• Benefits of intervention accrue to those at greatest underlying risk
# o
f M
Is P
reve
nte
d(P
er 1
000
pat
ient
s tr
eate
d fo
r 10
ye
ars)
Risk of MI or CHD Death (10 year)
Low Risk Moderate Risk High Risk
10% 20%
28
• Because relative risk reductions (25%) are the same, appropriate to extrapolate benefit across continuum
Coronary Heart Disease Risk Continuum
# o
f M
Is P
reve
nte
d(P
er 1
000
pat
ient
s tr
eate
d fo
r 10
ye
ars)
Risk of MI or CHD Death (10 year)
Low Risk Moderate Risk High Risk
HOT
PHS
BDT
PPP
TPT
Angina
REVASC. (CABG, PTCA)
2 Prevention
10% 20%
12
4
25
29
Coronary Heart Disease Risk Continuum
• Adverse event rate remains constant across underlying risk strata
# o
f M
Is P
reve
nte
d(P
er 1
000
pat
ient
s tr
eate
d fo
r 10
ye
ars)
Risk of MI or CHD Death (10 year)
Low Risk Moderate Risk High Risk
10% 20%
Adverse Event rate
12
4
25
30
Coronary Heart Disease Risk Continuum
• ASA should be indicated for all populations where benefits outweigh the risks (including moderate risk)
# o
f M
Is P
reve
nte
d(P
er 1
000
pat
ient
s tr
eate
d fo
r 10
ye
ars)
Risk of MI or CHD Death (10 year)
Low Risk Moderate Risk High Risk
HOT
PHS
PPP
TPT
Angina
REVASC.(CABG, PTCA)
2 Prevention
10% 20%
AdverseEvent rate
12
4
12
4
25
BDT
31
Extrapolation to Broader Population
• Statistically significant benefit in preventing MI among the trials conducted in secondary and primary prevention
• Homogeneity of Relative Risk Reductions for CHD across the high and low risk populations supports usefulness of aspirin therapy across risk continuum regardless of previous event
• Benefit to risk relationship is enhanced by: Limiting use to patients of at least Moderate Risk (> 10%) Excluding patients with increased risk of bleeding
32
Conclusions
• Robust findings support the utility of aspirin in preventing MI across the risk continuum
• A favorable benefit to risk relationship can be demonstrated in Moderate Risk patients Approx. 6-20 MIs can be prevented for every 2-4 GI bleeds
and 0-2 hemorrhagic strokes caused Benefit even greater in higher-risk patients
• Major public health benefits can be expected from proposed label change Increase number of patients assessed for CHD risk Reduce underutilization of treatment (primary and
secondary) Reduce long-term morbidity, mortality and costs
33
Evaluation of the Safety and Efficacy of Aspirin by Global Risk of CHD
Dr. Colin BaigentAntithrombotic Trialists’ (ATT) CollaborationUniversity of Oxford, UK
34
Presentation Overview
• ATT collaboration, history and objectives Rationale and definitions
• Antiplatelet therapy in HIGH-RISK patients Clear benefits in a wide range of patients
• Identification of MODERATE RISK patients who may benefit from aspirin Assessment of benefits Assessment of bleeding risks
• Conclusions
35
Pre-defined ATT outcomes
• ATT outcomes defined in mid 1980s, before most studies had started
• Primary outcome: “Serious Vascular Event” Non-fatal MI OR Non-fatal stroke OR Vascular death
• Secondary outcomes Non-fatal MI, Non-fatal MI or CHD death Stroke (non-fatal, fatal) Death (vascular, non-vascular) Major extracranial bleeding
36
ATT Collaboration: 2 sources of evidence
• Effects of antiplatelet therapy among HIGH-RISK patients (BMJ 2002; 324:71-86) One quarter reduction in serious vascular events among
a wide range of HIGH-RISK patients Benefits clearly outweigh bleeding risks Benefits similar irrespective of age, gender, blood
pressure, and presence of diabetes
• Effects of aspirin among MODERATE-RISK individuals in 5 “primary prevention” trials Aim was to assess whether “moderate-risk” individuals
benefit from aspirin Collaboration of study investigators Based on individual patient data Manuscript in preparation
37
HIGH-RISK patients
38
Benefit per 1000(SE):
A13.5%
A10.4%
A17.8%
A8.1%
C21.4%
C14.2%
C17.0%
C9.0%
C10.2%
0%
10%
20%
Prior MI Acute MI Priorstroke/TIA
Acutestroke
Other highrisk
CATEGORY
A = Antiplatelet therapy
C = Control
Average duration: 27 m
36(5)
1.3 m38(5)
29 m36(6)
0.7 m9(3)
22 m22(3)
Antithrombotic Trialists’ Collaboration, 2002
P-value: <0.00001 <0.00001 <0.00001 0.002 <0.00001
A8.0%
Absolute effects on vascular events in various high-risk groupsR
AT
E
39
Antiplatelet Therapy among HIGH-RISK Patients
By GENDER
37 (4) per 1000reduction
33 (7) per 1000reduction
02468101214161820
Male Female
Gender
% o
f p
atie
nts
40
0
5
10
15
20
25
<65 65+
Age
% o
f p
atie
nts
Antiplatelet Therapy among HIGH-RISK Patients
By AGE
32 (4) per 1000reduction
45 (7) per 1000reduction
41
Antiplatelet Therapy among HIGH-RISK Patients
By BP
32 (6) per 1000reduction
41 (7) per 1000reduction
0
5
10
15
20
25
<90 90+
Diastolic Blood Pressure
% o
f p
atie
nts
42
0
5
10
15
20
25
No Yes
Diabetes
% o
f p
atie
nts
Antiplatelet Therapy among HIGH-RISK Patients
By DIABETES Status
36 (3) per 1000reduction
38 (12) per 1000reduction
43
Extracranial Bleeding: HIGH-RISK Patients
• 1.6-fold increase in risk of extra cranial bleeds
• Absolute excess risk ~1 per 1000 per year
• Consistent across different high-risk groups
44
MODERATE-RISK patients
45
Characteristics of “Primary Prevention” Trials
BDS
(1988)
PHS
(1989)
TPT
(1998)
HOT
(1998)
PPP
(2001)
N 5139 22071 5085 18970 4495
Duration (yrs) 6 5 7 4 4
ASA dose (mg/day) 500 325* 75 75 100
Placebo control N Y Y Y N
Age (mean) 61 53 57 61 64
Women - - - 47% 57%
Prior vascular disease 8% 1% <1% 3% 4%
Diabetes 2% 2% 2% 8% 17%
*Alternate day aspirin
46
ATT Analysis of Primary Prevention Trials
• Individual patient data 5 trials involving over 55,000 subjects Extensive checking and validation of data
• Diverse patient populations Around one fifth of individuals at MODERATE-RISK
• Outcomes pre-defined by ATT Silent MI specifically excluded
• Pre-specified comparisons with post-MI and post-TIA patients
47
ATT: Effects on VASCULAR EVENTS
48
ATT: Effects on CHD EVENTS
49
ATT: Effects on NON-FATAL MI
50
ATT: Effects on STROKE
51
ATT: Effects on HEMORRHAGIC STROKE
52
ATT: Effects on VASCULAR DEATH
53
ATT: Effects on MAJOR EXTRACRANIAL BLEEDS
54
Benefit and Risk of Aspirin
In Primary & Secondary Prevention
Outcome Primary Prevention Secondary Prevention
Non-fatal MI 1/3 reduction 1/3 reduction
Any stroke NS 1/5 reduction
Vascular death NS 1/10 reduction
Major bleeds 2/3 increase 2/3 increase
55
Absolute Benefits of Aspirin on CHD EVENTS
In Primary and Secondary Prevention
0
1
2
3
4
5
6
Primary prevention
Secondary prevention
<10%* 10-20% >20%
Benefit per 1000 patientstreated per year
1 3 6
*10 year baseline risk
Eve
nts
Pre
ven
ted
56
Events Avoided or Caused
Per 1000 Individuals Treated with Aspirin for 5 Years
Avoided Caused
10-year risk CHD Ischemic Hemorrhagic Majorof CHD event event stroke stroke bleed
<10% 5 0 1 5
10-20% 14 0 1 5
>20% 25-50 25-50 1 5
57
Conclusions
• High-Risk Benefits clearly outweigh bleeding risks and use should be
encouraged regardless of history of previous event
• Moderate Risk Benefits sufficiently outweigh risks among moderate-risk
individuals (10-20% ten year risk) to warrant treatment Substantial public health benefit if aspirin extended to
moderate-risk individuals
• Low Risk Aspirin use is not appropriate if ten year CHD risk is less
than 10%
58
Women, Coronary Heart Disease (CHD) &the Role of Aspirin in Primary Prevention
C. Noel Bairey Merz, M.D.Medical Director and Endowed Chair,Women’s Health and Preventive CardiologyCedars-Sinai Medical CenterScientific Chair, NHLBI-sponsored WISE StudyLos Angeles, CA
59
Magnitude and Significance of the Problem• Since 1984, more women than men die annually of CHD
This will worsen with the continued aging of the U.S. population
60
Current Status of Primary Prevention in Women
1 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5106a3.htm , updated 06-15-02; 2 Eaker ED, et al., Circulation. Vol.88,No.4, Part 1, October 1993. 1999-2009; 3 The Women’s Health Book, Third Ed, 2002; 4 Elrodt G, et al. AHA Get with the Guidelines. Circulation 2003;108:IV-446
• Women are more likely to die of sudden death prior to hospital arrival (52%), compared with 42% for men1, and account for a disproportionate share of cardiovascular healthcare costs2
• 50% of women greater than 55 years old have serum cholesterol levels that are high risk ( 240 mg/dL); 1/3 of women in this group have a global CHD risk score of greater than 6%2
• Women see primary care physicians more often than men for both routine and symptom-related care, and are more compliant with preventive healthcare recommendations.3
• Yet, women are less likely to receive appropriate preventive care, including aspirin therapy, when indicated4
61
Efficacy of Low Dose Aspirin in Women
• Issues to Consider in Evaluating the Data:• “Special Population” treatment where women are
considered a minority subgroup, despite comprising the majority of both the general and CHD populations
• “Pedestal Treatment” for women where risk avoidance is factored relatively higher, shifting the perceived risk/benefit ratio such that effective treatments are less utilized
• No significant differences in magnitude of risk or benefit between women and men in either the primary or secondary prevention aspirin trials that included women
• No biological basis for a gender difference in aspirin benefit or risk
62
Women, CHD & the Role of Aspirin in Primary Prevention
• Conclusions The aging of America necessitates a focus on the
majority (women) for CHD prevention - not just politically correct
Risk stratification exists, women are amenable to preventive practices, yet therapies are underutilized compared to men
Similar favorable risk/benefit ratios for women and men for ASA as primary prevention
Opportunity exists today to close the evidence-based/practice gap, as well as to rectify “special population” and “pedestal” treatment for the largest group afflicted by CHD - women
63
Enhancing Appropriate Aspirin Utilization with CHD Risk-Based Therapy
Randall S. Stafford, MD, PhDAssistant Professor of MedicineProgram on Prevention Outcomes and Practices,Stanford Prevention Research CenterStanford, CA
64
Presentation Overview
• Rationale and Methods for Examining Aspirin Utilization
• Aspirin Use in Low, Moderate and High Risk Groups Disparities in Aspirin Use Explanation for Suboptimal Use Strategies for Enhancing Appropriate Utilization
65
Rationale for Study
• Concept of global risk implies that a continuum of risk exists that can be used to tailor intensity of management Patients at higher global risk should be treated more
aggressively across multiple risk reduction strategies
• Aspirin’s role in secondary prevention is well-established, but also of benefit in moderate risk patients without known CVD event Need to solidify physician recognition of risk stratification
as a key tool in disease management
• Little is known about current physician aspirin utilization practices
66
Specific Project Aims
• Evaluate 1992-2001 trends in aspirin use by cardiovascular disease risk status, focusing on moderate risk patients
• Identify patient and physician characteristics associated with aspirin use
67
Data Sources
• Federally-Conducted National Care Surveys Private physician offices (NAMCS) and hospital
OPD (NHAMCS) Patient visits as the unit of analysis Annual samples of 45-50,000 visits
• Visit-Specific Information About: Patient demographics and diagnoses Physician activities (tests, advice, referrals) New or continuing medications
• Validated against other national data sources
• Limitations
68
Definition of Cardiovascular Risk
• High Risk : Existing coronary heart disease or other clinical forms of
atherosclerosis (5% of total annual visits)
• Moderate risk : Diabetes mellitus (5%)
> 2 CHD risk factors among men < 45 and women < 55 or > 1 risk factors among men > 45 and women > 55 (15%)
• Low risk : (75%)
69
The Likelihood of Aspirin Use by Cardiovascular Risk
0%
10%
20%
30%
40%
50%
1992-93 1994-95 1996-97 1998-99 2000-01
Low Moderate Diabetes High
70
% Aspirin Use among Visits with Statins
by Cardiovascular Risk
0%
10%
20%
30%
40%
50%
1992-93 1994-95 1996-97 1998-99 2000-01
Moderate High
71
Factors Independently Associated with Aspirin Use
Significant Factors Odds Ratios
Cardiovascular Risk (ref: Low) Multiple risk factors 2.2 (1.7 3.0) Diabetes 3.3 (1.8 5.9) High 9.0 (6.4 12.7)
Patient Age (years) (ref: 20-44) 45-64 1.9 (1.4 2.7) 65-79 2.5 (1.8 3.6) 80 3.2 (2.1 5.0)
72
Factors Independently Associated with Aspirin Use
Significant Factors Odds Ratios
Patient Sex (ref: Male) Female 0.8 (0.7 0.9)
Medical Insurance (ref: Private) Medicare 1.2 (1.0 1.5) Medicaid 1.1 (0.9 1.5) Self-Pay 0.6 (0.4 1.0) Other 0.9 (0.6 1.4)
Physician Specialty (ref: Cardiology) IM 0.3 (0.2 0.5) GP/FP 0.2 (0.1 0.4) Other 0.2 (0.1 0.2)
73
Summary of Study Findings
• Aspirin is dramatically underused in the prevention of CHD in appropriate patients Minimal inappropriate use in low risk patients
• The extent of underutilization has improved only modestly in the past decade in spite of evidence
• Greater aspirin use was independently associated with higher cardiovascular risk, advanced age, male gender, health insurance coverage, and cardiologist care
74
Limitations
• Possible under-reporting of aspirin use
• While not perfect, best data available shows that aspirin is underused
75
What Causes Suboptimal Use Aspirin Use?
• Lack of knowledge about existing evidence
• Lack of incentives and/or accountability for evidence-based practice
• Patients and physicians focus on acute issues
• Balancing costs, risks and benefits not always straightforward
• Aspirin is not labeled for primary prevention despite available evidence of its benefits
76
How to Improve Appropriate Aspirin Use?
• Unambiguous aspirin labeling supporting appropriate use Expanded labeling to include intermediate-risk patients
• Physician and patient education and encouragement Better incentives for attaining recommended practices
• Employ case management to manage chronic issues and improve patient adherence
77
Aspirin in Primary Prevention For Risk
Eric J. Topol, MDProvost and Chief Academic Officer, Cleveland Clinic
Chairman, Department of Cardiovascular Medicine
Professor of Medicine and Genetics
78
The Body of Data
• 55,580 patients from 5 RCTs
79
The Body of Data
• 55,580 patients from 5 RCTs
• Diverse populations at risk is a major strength
80
The Body of Data
• 55,580 patients from 5 RCTs
• Diverse populations at risk is a major strength
• Unequivocal (>30%) of MI endpoint
81
The Body of Data
• 55,580 patients from 5 RCTs
• Diverse populations at risk is a major strength
• Unequivocal (>30%) of MI endpoint
• Post-hoc subgroup analysis is counter-productive
82
Professional Societies and Groups Supporting
• American Heart Association
• American College of Cardiology
• American Diabetes Association
• US Preventive Services Task Force
• Antithrombotic Trialists’ Collaboration
83
“Real World” Issues
• Empowered American consumers already accept low dose ASA for prevention
• > 20 Million Americans currently take ASA for prevention of MI
• Inconsistent message - Physician experts to lay community via Good Housekeeping, Reader’s Digest, Prevention, Ladies Home Journal, etc.
84
Acute MI in 2003 and the Future
• The pathophysiology involves platelet-thrombus as the proximate cause
• No sig. reduction in mortality in the past 10 yrs despite multiple treatments assessed in RCTs
• Once the MI has initiated, bad outcomes result
• The only meaningful strategy is to prevent the events
85
Who Should Be Recommended to Take Aspirin?
• Risk of > 0.6% per year recommended by USPSTF,
• Risk of > 1% per year recommended by AHA, ACC [35% reduction NFMI, 3/1000 /yr]
• Risk of > 2% per year has a striking benefit/risk ratio [43% reduction NFMI, 6/1000 /yr]
86
The Trade-Off Continues to Get Better
• Overriding MI vs. GI Bleeding events, which are not
• Preservation of efficacy for ASA at doses as low as 75 - 81 mg
• Less than half bleeding events encountered at low dose ASA (BRAVO, CURE)
87
Anchoring Issues for Primary Prevention
• The most important direction in the future of medicine
88
Anchoring Issues for Primary Prevention
• The most important direction in the future of medicine
• Ongoing large RCTs are assessing therapies in addition to ASA---the “runaway” concept
89
Anchoring Issues for Primary Prevention
• The most important direction in the future of medicine
• Ongoing large RCTs are assessing therapies in addition to ASA---the “runaway” concept
• ASA is the cornerstone of prevention of MI—not just 2° !
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