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Systematic Hospital - based Secondary Prevention

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Systematic Hospital - based Secondary Prevention The Stroke PROTECT Program Preventing Recurrence Of Thrombo-embolic Events through Co-ordinated – PowerPoint PPT presentation

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Title: Systematic Hospital - based Secondary Prevention


1
Systematic Hospital - based Secondary Prevention
  • The Stroke PROTECT Program
  • Preventing Recurrence Of Thrombo-
  • embolic Events through Co-ordinated
  • Treatment

2
Secondary Stroke Prevention Lecture Series
  • Overview of the PROTECT Program and Antiplatelets
    in Stroke Prevention
  • Statins and Lifestyle Modification Approaches
  • Stenting and Carotid Endarterectomy
  • Risk Factor Reduction in Hypertension and Atrial
    Fibrillation

3
Stroke A Major Public Health Burden
  • One stroke occurs in the US every 53 seconds
  • Third leading cause of death
  • gt150,000 deaths per year in US
  • gt750,000 new strokes per year in US
  • gt4,400,000 stroke survivors in US
  • Leading cause of adult disability
  • Most preventable of catastrophic conditions

4
Age and Gender-Specific Stroke Incidence
Northern Manhattan Stroke Study
931
857
688
650
629
468
392
184
175
76
46
42
13
8
7
4
Age Groups (y)
Sacco R et al. Am J Epidemiol. 1998147259-268.
5
Cumulative Risk of Stroke
Post-TIA ()
Post-Stroke ()
3 10 5 14 25 40
4 8 12 13 24 29
30 days 1 year 5 years
Sacco. Neurology. 199749(suppl 4)S39. Feinberg
et al. Stroke. 1994251320.
6
Prognosis After Transient Ischemic Attack (TIA)
1707 patients with TIA identified by emergency
department physicians
1.0
Stroke 10.5
0.9
Probability of Survival Free From Stroke and
Adverse Events
0.8
Adverse events 25.1
(stroke, cardiovascular hospitalization, death,
or recurrent TIA)
0.7
0.6
0
7
30
90
60
Days After TIA
Number of Patients at Risk Stroke 1001 1577 1527 1
480 1451 Adverse events 1001 1462 1361 1293 1248
Johnston SC, et al. JAMA. 20002842901-06.
7
Management of Stroke
  • The best approach towards reducing the immense
    burden that stroke places on our society remains
    prevention

8
Modifiable Stroke Risk Factors
  • Medical Conditions
  • Hypertension
  • Cardiac disease
  • Atrial fibrillation
  • Hyperlipidemia
  • Diabetes mellitus
  • Carotid stenosis
  • Elevated homocysteine
  • Prior TIA or stroke
  • Behaviors
  • Cigarette smoking
  • Heavy alcohol use
  • Physical inactivity

9
RF Control Impact on Stroke Prevention
  • gt750,000 strokes annually in the US
  • Preventable strokes
  • Hypertension 369,000
  • Hypercholesterolemia 150,000
  • Tobacco Use 91,500
  • Atrial Fibrillation 47,000
  • Heavy Alcohol Use 35,200
  • --Modified from Gorelick, Neuroepidemiology
    1997

10
Emerging Strategies
  • Atherosclerosis is responsible for the majority
    of ischemic strokes
  • Destabilization of the atheromatous plaque is a
    forerunner of ischemic stroke
  • This plaque is now the main focus for new
    directions in prevention and treatment of
    cerebrovascular atherosclerosis

11
Overlap of Vascular Disease in Patients With
Atherothrombosis
MI
Unstable angina
Ischemic stroke
PAD
Platelet adhesion, activation, and aggregation
Plaque rupture
Thrombus formation
Vascular events (MI, stroke, or CV death)
Ness J, Aronow WS. J Am Geriatr Soc.
1999471255-1256. Schafer AI. Am J Med.
1996101199-209.
12
Atherosclerotic Plaque

Unstable
Stable
Lumen
Endothelium
Lipid Rich Core
ThickFibrous Cap
Thin Fibrous Cap
Falk E et al. Circulation. 199592657671.
13
Stroke Subtypes
14
Stroke Subtypes
  • Frequency of High Risk Atherosclerosis Patients
    in Stroke
  • Large vessel 100 35
  • Small Vessel 80 16
  • Cardioembolic 60 15
  • Total 66

15
The Evidence - Practice Gap
  • Despite compelling scientific evidence and
    national treatment guidelines supporting the use
    of secondary prevention medical therapies, these
    treatments continue to be underutilized in CVD
    patients receiving conventional care

16
The Evidence Practice Gap in Implementing 2o
Prevention in Stroke Patients
  • Coverdell Acute Stroke Registries Pilot Data
  • 4 states, 7474 consecutive admissions, 2001-02
  • Lipid profile done 42
  • Antithrombotic at discharge 89
  • Warfarin for atrial fibrillation 67
  • Smoking cessation counseling 24
  • (Among patients with no MD documented
    contraindication)
  • --Frankel et al, Intl Stroke Conf, 2/03

17
The Evidence Practice Gap in Implementing 2o
Prevention in Stroke Patients
  • UHC Ischemic Stroke Benchmarking Project
  • 35 Academic Medical Centers, 1206 consecutive
    admissions, 2001
  • Antithrombotic at discharge 89
  • Warfarin for atrial fibrillation 57
  • Smoking cessation counseling 40
  • Patient educated about stroke 32
  • (Among patients with no MD documented
    contraindication)

18
Selected Barriers to Translating Clinical Trials
into Clinical Practice
  • Physician
  • Lack of knowledge of current evidence
  • Time constraints
  • Desire to avoid iatrogenic complications
  • Patient
  • Polypharmacy
  • Time
  • Financial
  • Intrinsic difficulty of lifestyle change
  • Health system
  • Uninsured and underinsured individuals
  • Care of chronic illness not organized
    systematically
  • High cost of health care
  • --Rich, JAMA 2002

19
Incentives for Change
  • NCQA/HEDIS/JCAHO/GOA reporting measures
  • Hospitals
  • Managed Care
  • Physicians
  • Consumer demand for quality care / report cards
  • AHA/ASA/JCAHO Stroke Center designation

20
Stroke Treatment System Goals
  • Implement initiatives to put evidence- based
    guidelines into action
  • Improve the quality of care for patients with
    established cerebrovascular disease
  • Reduce secondary events - and save lives
  • --Adapted from Fonarow, CHAMP, 2003

21
How about a Hospital Based System?
Problem Large CVD treatment gap and poor patient
compliance with conventional management
Solution In-hospital initiation of therapy with
excellent treatment rates and long term patient
compliance
Simple, Rapid, and Most Importantly Effective
22
Why a Hospital Based System?
  • Patients
  • Patient Capture Point
  • Have patients/family attention teachable
    moment
  • Predictor of care in community
  • Hospital Structure
  • Standardized processes/protocols/orders/teams
  • JCAHO
  • Process Improvement Examples
  • HCFA--Peer Review Organizations
  • --Adapted from Fonarow, CHAMP, 2003

23
Stroke/TIA Patient Flow in the Hospital
Advocate/Champion
Inpatient Care
Group Practice
Outpatient Care
Medical Ward
Quality Control
Stroke Unit
Neurologist
850,000
NICU/ICU
660,000
Acute Cerebrovascular Event
Discharge Nurse
Primary Care MD
ED
Neurology
Medicine
LOST
Discharged 25,000
Telemetry
Inpatient Rehab
Pharmacy
Outpatient Rehab
15
Protocol development process
Implementation
24
Challenges to In-Hospital Initiation of Secondary
Prevention Strategies
  • SOLUTIONS
  • 1. Education and mobilizing case management
    teams
  • 2. Hospital is the capture point for patients
    with acute disease
  • 3. Preprinted orders, testing per protocol
  • 4. Joint Commission, NCQA, PROs will be
    measuring and reporting
  • 5. GWTG Stroke, PROTECT
  • 6. UCLA PROTECT demonstrates improved treatment
    rates
  • BARRIERS
  • 1. Communication gaps - neurologists vs PCPs
  • 2. Lack of ownership - acute vs chronic disease
    dilemma
  • 3. Poor standardization of orders, testing
  • 4. Lack of financial incentives
  • 5. Lack of tools/resources
  • 6. Lack of proof of concept
  • --Adapted from Fonarow, CHAMP, 2003

25
Challenges to a Hospital Based System
this will not work in a community hospital
the neurologists will not agree to this
the primary care physicians will not agree to this
we can not get a consensus
the managed care organization will not pay for it
patients do not want to be on a lot of medications
there is not enough time
the lipid panel in not accurate when drawn in the
hospital
it may not be safe to start blood pressure
lowering medications in hospitalized patients
it will cost too much
this will benefit the competition
what about the liability
the hospital administration will not pay for it
it will take too much time
there are exceptions x, y, and z
it is too hard to get things through the hospital
committee
the patients should all be followed in my lipid
clinic
the physicians at my hospital do not like
cookbook medicine
we do not have anyone to collect this data
  • --Adapted from Fonarow, CHAMP, 2003

26
UCLA Stroke PROTECT Program
  • Novel and aggressive hospital-based quality
    improvement program designed to reduce the
    devastating consequences of recurrent stroke
    through improved use of evidence-based secondary
    prevention treatments

27
Hypothesis
  • In-hospital initiation of evidence-based
    secondary stroke prevention therapies would
    result in improved physician adherence, patient
    compliance, and treatment rates both at time of
    discharge and during longer term follow-up.

28
Design
  • Focused on achieving 4 behavioral goals 4
    pharmacologic goals in all cervicocephalic
    atherothrombotic disease patients prior to
    hospital discharge
  • Use of program tools including preprinted orders,
    simple guidelines, and prospective monitoring of
    treatment use
  • Started in 2002 and current template of care at
    UCLA

29
Eligibility
  • Inclusion Criteria
  • Diagnosis of ischemic stroke or transient
    ischemic attack 
  • Extent of participation will depend on patients
    stroke sub-type and co-morbid vascular risk
    factors   
  • Exclusion Criteria
  • Intracranial Hemorrhage

30
Program Goals
  • Appropriate Hospital Initiation and Maintenance
    of
  • Antithrombotic
  • ACE Inhibitor/ ARB
  • Statin
  • Thiazide diuretic
  • Exercise Education
  • Diet Education
  • Smoking Cessation
  • Awareness of Stroke Warning signs

31
Antithrombotics
  • Treatment of choice for prevention of strokes due
    to large vessel atherosclerotic disease and
    intracranial branch atheromatous (lacunar)
    disease
  • Current guidelines recommend daily therapy with
    either aspirin, clopidogrel, or
    aspirin/dipyridamole as first-line agents
  • Albers et al, Chest 2001

32
Statins
  • FDA New Labeling (based on HPS study)
  • April 17, 2003
  • Indicated for patients with stroke or evidence
    of cerebrovascular disease
  • All patients with atherosclerosis, regardless of
  • baseline LDL unless contraindicated, should
  • be started on a statin

33
ACE Inhibitors/ Angiotensin Receptor Blockers
  • All patients with atherosclerosis regardless of
    blood pressure, unless contraindicated should be
    started on an ACEI/ ARB. These agents reduce
    blood pressure have potent vascular effects
    including
  • Increased vascular compliance
  • Regression of periarteriolar collagen area and
    total interstitial collagen volume density
  • Reduction in the arteriolar wall area
  • Normalization of resistance artery structure

34
Thiazide Diuretics
  • Thiazide-type diuretics should be used in drug
    treatment for most patients with uncomplicated
    hypertension, either alone or combined with drugs
    from other classes.
  • Recurrent stroke rates are lowered by the
    combination of an ACE inhibitor and thiazide-type
    diuretic.

JNC 7 Report, JAMA 2003
35
Medical Regimen Follow-up
  • Continuation of the therapies targeting the
    underlying atherosclerosis disease process
    markedly improves clinical outcome in Stroke
    patients with atherosclerosis.
  • The continued beneficial therapies prescribed
    should be strongly reinforced during patient
    follow-up.

36
Medication Discontinuation Rates
  • Various randomized trials of antithrombotic
    agents in secondary stroke prevention have shown
    the efficacy of these agents and included data on
    side effects and dropout rates.
  • However, there is a paucity of published data on
    adverse events and discontinuation rates
    following initiation of these agents in a
    non-study setting.

37
VA Greater Los Angeles Healthcare System
VAGLAHS Study
  • The Incidence of Discontinuation of Clinical
    trial proven Antithrombotic therapies in the
    Secondary Prevention of Stroke

Dergalust et al 2003
38
VAGLAHS Study - Objective
  • Retrospective quality assurance review to
    determine the frequency with which extended
    release dipyridamole/aspirin, clopidogrel and
    warfarin are discontinued after being initiated
    for secondary stroke prevention and to determine
    the reasons for their discontinuation.

Dergalust et al 2003
39
VAGLAHS Study Methods/ Design
  • Data was collected for 700 patients VA GLA
    Healthcare system for the period of January 2000
    to December 2001.
  • 528 of the 700 patients met inclusion criteria.
  • All patients had to be diagnosed with a stroke or
    a TIA in the VAGLAHS and were on extended
    release dipyridamole/aspirin, clopidogrel or
    warfarin for secondary stroke prevention
  • Primary Endpoint Permanent discontinuation of
    the antithombotic agent for any reason

Dergalust et al 2003
40
VAGLAHS Study ResultsDuration of Therapy
Dergalust et al 2003
41
VAGLAHS Study Results Incidence of
Discontinuation
  • Antithrombotic therapy was discontinued in 27.57
    of the patients
  • Reasons for discontinuation included
  • Non compliance
  • MD error
  • MD preference
  • Bleeding complications
  • Other adverse effects
  • Patient preference

Dergalust et al 2003
42
VAGLAHS Study Results Reason for Discontinuation
Dergalust et al 2003
43
VAGLAHS Study - Conclusions
  • Physician error involved scenarios such as
    insufficient follow-up, inattention to the need
    for refills or prescription renewal, poor
    communication between the specialist and primary
    care provider, and system error.
  • Our study shows that inappropriate
    discontinuation of antithrombotic therapy is not
    uncommon in a stroke-prone population and the
    most common cause for it is non-compliance.

Dergalust et al 2003
44
PROTECT Tools
  • Stroke center staff pocket card
  • Preprinted Order Sheets
  • Clinical Pathways/ Care Maps
  • Nursing staff interdisciplinary stroke patient
    education record
  • Patient information packet
  • Template letters to primary/ referring physicians
  • Lab requisition sheet
  • Patient self monitor post discharge log
  • Phone and clinic follow-up records
  • Data abstraction form
  • Stroke PROTECT website

45
PROTECT Website Contents
  • Program Overview algorithms, outcome measures,
    analysis
  • Program Evidence
  • Program Results
  • Getting Started
  • Program Tools - downloadable
  • FAQ
  • Patient Prevention Information
  • Power Point slides - downloadable
  • References
  • Useful links

46
PROTECT Systematic Implementation of Secondary
Stroke Prevention Algorithm
47
PROTECT Outpatient Algorithm
48
PROTECT - Outcome Measures
  • Compliance with program goals documented
  • at discharge, days 14, day 90 and at 1 year
  • Vascular event (including stroke, TIA,
    myocardial infarction, and peripheral arterial
    occlusion)
  • at day 90, and at 1 year
  • Medication treatment complications
  • at day 14, day 90 and at 1 year

49
Impact of PROTECT pilot phase on Treatment Rates
at Discharge
--Ovbiagele et al, Stroke 2003
50
Impact of PROTECT on Treatment Rates at Discharge
51
PROTECT - Day 90 Medication Compliance Rates
Percentage
Ovbiagele et al 2003
52
PROTECT Day 90 Compliance Rates with Lifestyle
Interventions and all 8 Goals
Percentage
Ovbiagele et al 2003
53
Clinical Significance
  • Initiation and maintenance of proven medical and
    behavioral interventions in order to reduce
    future strokes
  • Simultaneous reduction in occurrence of
    myocardial infarction and peripheral arterial
    occlusion
  • Active involvement of the patient, family and
    primary care physician
  • Applicability at the community hospital level

54
Whats Involved in Starting a Hospital Based
Treatment Program
  • Collect baseline data or use existing data source
  • E.g. collect data with discharge nurse, medical
    student, etc.
  • Appoint team to develop treatment algorithm,
    preprinted orders, discharge forms
  • Present at lectures and staff in-services
  • present results
  • review successes and failures
  • lead discussion regarding recommendations on
    protocol improvement
  • Revise protocol to close Gaps
  • Communicate revisions to key departments
  • Repeat cycle every quarter CQI

55
Continuous Quality Improvement (CQI) Process
Assess CVD Treatment Rates
Evaluate Assessment
Implement Refined Protocol
Refine Protocol
56
Hospital BasedContinuous Quality Improvement
(CQI) Process
  • Mobilize GWTG Initiative
  • Establish Buy In
  • Identify Champions
  • Build Team
  • Plan Prep Program
  • Attend CME Program
  • Develop Hospital Plan
  • Assign Roles Responsibilities
  • Monitor Support
  • Collect Report f/u Data
  • Review Improve Process
  • Implement Program
  • Establish D/C Protocol
  • Collect Baseline Data
  • Obtain consensus

57
What is the AHAGet With the Guidelines -
Stroke Program ?
  • Implemented by AHA Affiliates/Volunteers who will
    mobilize advocacy networks at the Affiliate level
    to
  • Implement CME-driven educational programs
  • Provide workshops for dissemination of guidelines
  • Develop care maps
  • Formalize a national discharge protocol
  • Implement discharge protocols in hospital setting
  • Identify best practices for AHA recognition
    awards
  • Develop and disseminate reports and publications
  • Measure changes and report outcomes data
  • Drive impact into communities

58
GWTG Tools and Resources
  • AHA/ASA Guidelines
  • AHA National Discharge Protocol/Discharge Form
    Template
  • Care maps - ED, Ward, etc.
  • CME programs
  • AHA National teleconferences
  • Public Service Announcements
  • National and regional advocates

59
http//www.americanheart.org/.
60
Stroke PROTECT Summary
  • The PROTECT Program has demonstrated for the
    first time that Stroke risk-factor modification
    and treatment can be systematically integrated
    into the treatment provided during stroke
    hospitalization utilizing existing resources and
    medical personnel
  • PROTECT appears to be considerably more effective
    than conventional guidelines and care.

61
Formation of the Platelet Plug
Adhesion
Aggregation
1
3
Activated Gpllb/llla
Fibrinogen
Platelets
von Williebrand Factor/Gplb bind
Collagen Gpla/lla bind
Lipid core
Activation
Platelet Plug
2
4
Thrombin
ADP
5 HT
TXA2
Kumar A et al. Exp Opin Invest Drugs.
1997612571267.
62
Oral Antiplatelet Agents Different Mechanisms of
Action
dipyridamole
ADP adenosine diphosphate, TXA2 thromboxane
A2, COX cyclooxygenase. Schafer AI. Am J Med.
1996101199-209.
63
Beyond Aspirin Antiplatelet Agents for Secondary
Prevention
  • Clopidogrel
  • Aspirin/ ER Dipyridamole
  • Aspirin Clopidogrel

64
Clopidogrel CAPRIE Study
  • Clopidogrel 75 mg vs aspirin 325 mg
  • 19,185 patients with recent vascular event
  • Primary endpoint stroke, MI, vascular death
  • Mechanism inhibition of platelet ADP receptor

65
CAPRIE StudyEfficacy of Clopidogrel in Primary
AnalysisMI, Ischemic Stroke, or Vascular Death
(N19,185)
8.7 Overall Relative RiskReduction1
Aspirin 325 mg qd
16
Event Rate per Year
Clopidogrel 75 mg qd
12
5.832
Cumulative Event Rate ()
8
5.332
4
P 0.0451
0
0
3
6
9
12
15
18
21
27
24
30
33
36
Months of Follow-Up
Although the statistical significance favoring
clopidogrel bisulfate over aspirin was marginal
(P 0.045, based on orall incidence of primary
outcome events 9.78 for clopidogrel vs 10.64
for aspirin), and represents the result of a
single trial that has not been replicated, the
comparator drug, aspirin, is itself effective (vs
placebo) in reducing cardiovascular events in
patients with recent MI or stroke. Thus, the
difference between clopidogrel and placebo,
although not measured directly, is substantial.
66
Outcome Events of the Primary Analysis
Clopidogrel (n9599)
Aspirin (n9586)
Ischemic stroke(fatal or not)
438
461
275
333
MI (fatal or not)
Other Vascular Death
226
226
939
1020
Total
For the composite end point of MI, ischemic
stroke, and vascular death. PLAVIX Prescribing
Information.
67
Clopidogrel
  • No increased risk of neutropenia
  • Less bleeding risk vs. aspirin

68
TTP and Thienopyridines
  • General incidence 3.7/million
  • Mortality with prompt treatment 10-20
  • 80-90 prior to plasmapheresis
  • Ticlopidine incidence 1/1600-5000
  • Clopidogrel incidence 1/15,000-1/100,000

69
ESPS-2 Study Design
  • Multicenter, randomized, double-blind trial
  • 6602 patients with hx of stroke or TIA
  • Primary endpoint stroke or death at 2 yrs
  • 4 tx arms ASA (25 mg BID)
  • ER-Dipyridamole (200 mg BID)
  • ASA ER-Dipyridamole
  • Placebo

70
ESPS-2 Results Stroke-Free Survival

100
95
ASA/ER-DP
Patients Without Stroke ()
90
ASA
ER-DP
85
Placebo
80
6
12
18
24
Time (months)
71
ESPS-2 Results Notable Side Effects on Treatment

100
Placebo
ASA
80
ER-DP
60
ASA/ER-DP
Patients Reporting ()




40
20


0
Headache
GI Events
Dizziness
Bleeding Events
Significantly associated with treatment
according to factorial analysis.
72
ACCP Antiplatelet Guidelines
  • Acceptable options for initial therapy
  • Aspirin (50-325 mg qd)
  • ASA extended release dipyridamole (25-200 mg
    bid)
  • Clopidogrel (75 mg qd)

Albers et al, Chest 2001
73
Rapid and Synergistic Effect of Clopidogrel on
top of ASA (Healthy Volunteers)
Mean reduction of platelet deposition compared
with ASA alone
C75ASA vs ASA alone
C300ASA vs ASA alone
pNS
Mean reduction ()
80
plt0.001vs ASA
p0.01
plt0.001vs ASA
70
plt0.001vs ASA
60
50
p0.03vs ASA
p0.03
40
30
p0.04vs ASA
20
10
0
Day 1 1.5 hrs
Day 1 6 hrs
Day 10 6 hrs
-10
n18 for all comparisons
Cadroy Y et al Circulation 200010128232828
74
CURE Trial Design
300 mg loading 75 mg o.d. dose
Clopidogrel(6,250 patients)
Patients with Acute CoronarySyndrome
Aspirin 75-325mg
R
3 months double-blind treatment 12 months
(UA or MI Without STelevation)
Aspirin 75-325mg
Placebo 1 tab o.d.(6,250 patients)
Day 1
6 m. Visit
9 m. Visit
3 m. Visit
1 m. Visit
Discharge Visit
12 m.or Final Visit
loading dose
75
Cumulative Hazard Rates for CV Death/MI/Stroke
76
CURE Benefit of Clopidogrel in Patients With a
History of Stroke
RRR 26 (95 CI 0.50-1.10)
Placebo
Clopidogrel
25
22.4
20
RRR 20 (95 CI 0.71-0.90)
17.9
15
MI, Stroke, or CV Death ()
10
11.0
8.9
5
0
No Previous Stroke (n12,055)
Previous Stroke (n506)
In addition to standard therapy (including
aspirin). Plavix (clopidogrel bisulfate)
Prescribing Information.
77
CURE Study Bleeding Results
Clopidogrel Aspirin n6259 ()
Placebo Aspirin n6303 ()
Event
P Value
.001 .13 .005 lt.001
Major bleeding
Life-threatening Other major bleeding
Minor bleeding
2.7 1.8 1.0 2.4
3.7 2.2 1.6 5.1
Other standard therapies were used as
appropriate. Plavix (clopidogrel bisulfate)
Prescribing Information.
78
Upcoming Prevention Trials
  • ESPRIT
  • Anticoagulants, ASA plus dipyridamole, and ASA
    alone
  • MATCH
  • Clopidogrel plus ASA combination vs clopidogrel
    plus placebo combination
  • CHARISMA
  • High risk prevention
  • Clopidogrel / ASA
  • Secondary Prevention of Small Subcortical Stroke
    (SPS3)
  • Lacunar infarcts
  • Factorial design ASA/clopidogrel
  • Strokes, vascular events, cognitive decline
  • PRoFESS
  • ER-dipyridamole/ASA vs clopidogrel plus ASA

79
Clinical ImpactAntiplatelet
  • Antiplatelet therapy reduces the risk of stroke,
    MI, and vascular death in populations at risk
  • Antiplatelet therapy should be applicable to most
    patients with stroke
  • Combination therapy of aspirin with other
    antiplatelet agents may be more effective than
    aspirin alone
  • Additional trials are underway

80
How Bad is a Major Stroke?Elders at Risk for
Stroke (1183, TTO), --Samsa et al, Am Heart J 1998
Worse than death
Equivalent to being well
Equivalent to death
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