ORIGINAL CONTRIBUTION

Efficacy of Aspirin Plus Extended-Release

Dipyridamole in Preventing Recurrent Stroke
in High-Risk Populations
Ralph L. Sacco, MS, MD; Juhani Sivenius, MD, PhD; Hans-Christoph Diener, MD, PhD

Objective: To assess the efficacy of aspirin plus extended-
release dipyridamole compared with aspirin alone for the
prevention of recurrent stroke among high-risk groups.
Design: A post hoc analysis was conducted using data
from the European Stroke Prevention Study 2. Rates of
annual strokes and vascular events were determined for
the aspirin plus extended-release dipyridamole group
(n=1650) and the aspirin-only group (n=1649), and were
stratified by risk subgroup and univariate risk factors.
Stroke models from the Framingham Study and the Stroke
Prognostic Instrument II were applied to subjects in the
European Stroke Prevention Study 2 to categorize pa-
tients into risk groups.
Results: Compared with aspirin alone, aspirin plus ex-
tended-release dipyridamole demonstrated a more pro-
nounced efficacy in reducing the risk for stroke and vas-
cular events among patients younger than 70 years; those
with hypertension, prior stroke, or transient ischemic at-
tack; current smokers; and those with any prior cardio-
vascular disease. Relative hazard reductions favored the
combination of aspirin plus extended-release dipyridam-
ole, and were greatest for the high-risk Framingham Study
group and the moderate-risk Stroke Prognostic Instru-
ment II subgroup.
Conclusion: Aspirin plus extended-release dipyridam-
ole is more effective than aspirin alone at preventing
stroke, and the difference in efficacy increases in higher-
risk patients.
Arch Neurol. 2005;62:403-408

Author Affiliations:
Departments of Neurology and
Epidemiology, College of
Physicians and Surgeons and
the Mailman School of Public
Health, Columbia University,
Neurological Institute, New
York, NY (Dr Sacco);
Department of Neuroscience
and Neurology, Kuopio
University Hospital, Brain
Research and Rehabilitation
Center Neuron, Kuopio,
Finland (Dr Sivenius); and
Department of Neurology,
University Hospital Essen,
Essen, Germany (Dr Diener).
Financial Disclosure: Drs Sacco
and Diener have received
honoraria as consultants and
speakers from Boehringer
Ingelheim, Sanofi-Synthelabo,
and Bristol-Myers Squibb.
Dr Sivenius has received
honoraria from Boehringer
Ingelheim.
S
TROKE IS THE THIRD LEADING
cause of death in most devel-
oped countries and a lead-
ing cause of serious long-
term disability.1 In the United
States, 750 000 persons have a stroke an-
nually, of whom about 200000 have re-
current stroke.1 Among patients with a first
stroke, 80% to 85% survive.2,3 These pa-
tients face a 5% to 15% risk for recurrent
stroke in the first year following the acute
stroke, during which the highest risk ex-
ists in the weeks immediately following the
initial event.2 Because age is an impor-
tant nonmodifiable risk factor for stroke,
the decline in stroke-related mortality com-
bined with the increase in life expec-
tancy for the US population will certainly
increase the number of persons at risk for
recurrent stroke and stroke’s related dis-
ability and medical care costs.4
Fortunately, observational epidemio-
logical studies and controlled clinical trials
have provided substantial evidence that the
risk of recurrent ischemic stroke can be re-
duced.5 Various modifiable risk factors,
such as hypertension, cardiac disease, and
dyslipidemias, can be controlled to help re-
duce the risk for recurrent stroke. Four
antiplatelet agents have demonstrated
efficacy for preventing recurrent stroke,
including aspirin, ticlopidine hydrochlo-
ride, clopidogrel bisulfate, and aspirin plus
extended-release dipyridamole.6 The stud-
ies that produced these findings have re-
sulted in updates to the guidelines for
secondary stroke prevention from the
American Heart Association and the Ameri-
can College of Chest Physicians.5,7
CME course available at
www.archneurol.com
Despite the revised recommendations,
expert opinion varies considerably regard-
ing the relative efficacy of antiplatelet agents
for prevention of recurrent stroke.8 This un-
certainty is largely a result of the absence
of direct comparisons of combination an-
tiplatelet therapy and the marked variabil-
ity in the choice of primary end points for
individual trials.8 Moreover, certain agents
or combinations of agents may be pre-

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Table 1. Definitions of Vascular Risk Variables
in the European Stroke Prevention Study 2 Trial
Variable Definition
Prior cerebrovascular Prior stroke or TIA
event
IHD A history of ischemic heart disease or MI or
electrocardiographic evidence of coronary
ischemic signs or residual signs of
previous infarction
PVD A history of PVD, the absence of 1 or more
peripheral pulse (carotid, radial, femoral,
or popliteal artery), or the presence of
1 or more vascular murmurs (carotid or
femoral artery)
Hypertension A history of hypertension, baseline systolic
blood pressure ⬎160 mm Hg, baseline
diastolic blood pressure ⬎95 mm Hg, or
current antihypertensive treatment at
baseline (centrally acting antihypertensive
agents, angiotensin-converting enzyme
inhibitors, diuretics in the absence of
cardiac failure, ␤-blockers in the absence
of IHD, or calcium channel blockers in the
absence of IHD)
Hypercholesterolemia A history of hypercholesterolemia, a
baseline cholesterol level ⬎290 mg/dL
(⬎7.5 mmol/L), or current treatment with
hypolipidemic agents at baseline
Cardiovascular disease IHD, PVD, cardiac failure, or hypertension
TIA A focal disturbance of the cerebral
circulation that resulted in a clinical
neurological deficit recovering within 24 h
without functional impairment at standard
clinical neurological examination
Stroke A focal disturbance of the cerebral
circulation that resulted in a functional
neurological deficit lasting ⬎24 h
Sudden death Death occurring within approximately 24 h
after the appearance of symptoms; other
cardiovascular deaths included deaths
attributable to cardiac arrhythmia,
hemorrhage, and peripheral vasculopathy;
and other nonvascular deaths included
those attributable to miscellaneous
causes, such as diabetes mellitus and
renal failure
Vascular event First of nonfatal stroke, nonfatal MI, or
vascular death, where vascular death
includes fatal stroke, fatal MI, death due
to other vascular events or cardiac failure
usually within 30 d of the event, sudden
death, hemorrhagic death (noncerebral
fatal bleeding), or death of uncertain or
unknown cause occurring within 24 h
after the onset of symptoms
Abbreviations: IHD, ischemic heart disease; MI, myocardial infarction;
PVD, peripheral vascular disease; TIA, transient ischemic attack.
ferred in patients with varying degrees of risk for recur-
rent stroke and cardiovascular outcomes.
To assess the efficacy of aspirin plus extended-
release dipyridamole compared with aspirin alone to pre-
vent recurrent stroke, we performed post hoc analyses
of the European Stroke Prevention Study 2 (ESPS-2) trial.
Our aim was to evaluate the reduction in risk for recur-
rent stroke in various risk factor subgroups and in sub-
groups at high risk for recurrent stroke estimated from
externally validated measurement scores.
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METHODS
The ESPS-2 was a multicenter, randomized, placebo-
controlled, double-blind, 2-by-2 factorial trial designed to as-
sess the safety and efficacy of low-dose aspirin, extended-
release dipyridamole, and the 2 agents combined for the
secondary prevention of ischemic stroke. The full details of the
study design are described by Diener and colleagues9; in brief,
the study population comprised 6602 patients older than 18
years (mean age, 66.7 years) who had experienced a transient
ischemic attack (TIA) (24%) or an ischemic stroke (76%) within
the preceding 3 months. Patients were randomly assigned to
receive aspirin alone (50 mg/d), extended-release dipyridam-
ole alone (400 mg/d), the 2 agents in a combined formulation,
or placebo, and were followed up every 3 months for 2 years.
Primary end points were stroke (fatal and nonfatal) and death
from all causes.
At baseline, various data were collected regarding demo-
graphics and vascular risk factors, such as history of hyperten-
sion, diabetes mellitus, myocardial infarction (MI), cigarette
smoking, stroke, or TIA. These variables were defined by his-
tory through subject interview and baseline medical record re-
view. Any cardiovascular disease was defined as persons hav-
ing experienced cardiac failure or having hypertension, ischemic
heart disease, or peripheral vascular disease. Definitions of vas-
cular risk factors from ESPS-2 are listed in Table 1.
We conducted our post hoc analysis with external stroke
models from the Framingham Study10 and the Stroke Prognos-
tic Instrument II11 (SPI-2) to compute estimated risk catego-
ries based on the ESPS-2 baseline variables. We converted the
risk variables to risk scores using the method in the Framing-
ham Study.10 The Framingham stroke risk score was devel-
oped from the Framingham cohort to calculate an estimated
probability of stroke (primarily first stroke) in men and women.
For the Framingham Study model, the 10-year stroke prob-
ability was classified as low (ⱕ0.15) or high (⬎0.15) using the
following variables: age, systolic blood pressure, antihyperten-
sive therapy, diabetes mellitus, cigarette smoker, cardiovascu-
lar disease, atrial fibrillation, and left ventricular hypertrophy.
The SPI I was developed specifically to predict stroke or death
among stroke or TIA survivors.12 The SPI-2 model, which uses
new predictive variables and recalculated point scores for all
component variables, was developed from the Women’s Estro-
gen for Stroke Trial cohort, and its enhanced performance has
been demonstrated and validated in other external cohorts.11
The SPI-2 score was classified as low (0-3), middle (4-7), or
high (8-15) using the following variables: congestive heart fail-
ure, diabetes mellitus, prior stroke, older than 70 years, stroke
for enrollment event, severe hypertension, and coronary ar-
tery disease. Stroke risk scores were calculated according to these
models for each subject in ESPS-2, and subjects were catego-
rized into risk strata based on these scores.
The new analyses examined the annual stroke and vascu-
lar event rates for the aspirin-alone group (n=1649) and the
aspirin plus extended-release dipyridamole group (n=1650),
stratified by the patient’s risk subgroup and univariate risk fac-
tors. Subjects with missing baseline data (n=103) for risk model
stratification (Framingham Study or SPI-2) were eliminated from
this analysis. Annual event rates were defined as the number
of first events divided by the total number of patient-years in
the study. The primary focus of the study was stroke out-
comes (fatal or nonfatal). Stroke or vascular events were de-
fined as the first occurrence of nonfatal stroke, nonfatal MI, or
vascular death. Vascular death was defined as fatal stroke, fa-
tal MI, death due to other vascular events or cardiac failure usu-
ally within 30 days of the event, sudden death, hemorrhagic
death (noncerebral fatal bleeding), or death of uncertain or un-
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 Table 2. Annual Stroke Rates and RHRs in the European Stroke Prevention Study 2 Trial,
Stratified by Baseline Univariate Risk Factors

Aspirin Plus
Risk Factor No. of Subjects Extended-Release Dipyridamole* Aspirin Alone* RHR (Lower, Upper CL), % P Value
Age ⬎70 y
No 1911 3.3 5.2 33.8 (8.5, 52.1) .01
Yes 1285 8.3 10.2 18.8 (−7.5, 38.7) .15
Sex
Male 1853 5.4 7.2 24.3 (0.4, 42.5) .05
Female 1343 5.0 6.9 27.8 (−0.6, 48.2) .05
Hypertension
No 1277 4.6 5.7 19.5 (−15.9, 44.1) .24
Yes 1919 5.7 8.0 28.8 (7.6, 45.1) .01
Diabetes mellitus
No 2723 5.0 6.7 25.4 (5.6, 41.1) .01
Yes 473 6.9 9.7 28.5 (−15.9, 55.9) .17
Previous MI
No 2915 5.1 6.8 24.9 (5.9, 40.0) .01
Yes 281 6.6 10.6 36.8 (−19.8, 66.7) .16
Atrial fibrillation
No 3000 4.9 6.8 27.1 (8.7, 41.7) .006
Yes 196 11.3 13.6 18.4 (−57.0, 57.6) .54
Any cardiovascular disease
No 730 3.6 4.4 18.2 (−39.9, 52.2) .46
Yes 2466 5.8 7.9 27.3 (8.4, 42.2) .007
Current smoker
No 2411 5.3 6.7 19.7 (−2.6, 37.2) .08
Yes 785 5.0 8.5 40.9 (10.2, 61.1) .01
Prior stroke or TIA
No 2311 5.0 5.7 12.2 (−14.4, 32.7) .33
Yes 885 6.1 11.0 44.6 (20.6, 61.3) .001
Qualifying event
TIA 776 3.6 4.1 11.2 (−49.9, 47.5) .66
Stroke 2420 5.8 8.1 27.8 (8.9, 42.7) .006

Abbreviations: CL, confidence limit; MI, myocardial infarction; RHR, relative hazard reduction; TIA, transient ischemic attack.
*Data are given as annual percentage of subjects in each group who experienced a stroke.

known cause occurring within 24 hours after the onset of symp-
toms. Relative hazard reductions were calculated using Cox pro-
portional hazards models.
RESULTS
Overall, the ESPS-2 results demonstrated that the combi-
nation of aspirin plus extended-release dipyridamole com-
pared with aspirin alone among TIA or stroke patients was
superior in reducing the risk of stroke (relative risk re-
duction, 23%; 95% confidence interval, 9%-37%; P=.006)
and stroke or vascular events (relative risk reduction, 22%;
95% confidence interval, 7%-36%; P=.003). The efficacy
of aspirin plus extended-release dipyridamole compared
with aspirin alone for various baseline subgroups is shown
for the outcome of stroke in Table 2 and for the out-
come of stroke or vascular events (including vascular death)
in Table 3. Compared with aspirin alone, treatment with
aspirin plus extended-release dipyridamole resulted in sub-
stantial relative hazard reductions for stroke within some
of the specific risk factor subgroups. Relative hazard rates
favored the combination therapy in each of these sub-
groups, with a more pronounced efficacy observed among
those younger than 70 years; those with hypertension, prior
MI, prior stroke or TIA, and any prior cardiovascular dis-
ease; and current smokers. The greatest relative hazard re-
duction (44.6%) was found among patients with a stroke
or TIA before the qualifying event. Patients with a history
of MI who were treated with aspirin plus extended-
release dipyridamole had a 36.8% relative hazard reduc-
tion of stroke compared with those taking aspirin alone.
Patients with any prior cardiovascular disease had a 27.3%
lower stroke hazard while taking aspirin plus extended-
release dipyridamole compared with aspirin alone. The rela-
tive hazard reduction for stroke was 11.2% for those with
TIA as a qualifying event and 27.8% for those random-
ized after stroke.
The combined outcome of stroke or vascular events is
shown in Table 3. The results show that patients using as-
pirin plus extended-release dipyridamole experience sub-
stantial relative hazard reductions for the end points of
stroke or vascular events. Greater relative hazard reduc-
tions were found among those with prior stroke or TIA,
previous MI, and among current smokers. The relative haz-
ard reduction was 24.8% for those with TIA as a qualify-
ing event and 18.6% for those randomized after stroke. Some
subgroups, such as those with atrial fibrillation, were small,
which resulted in wide confidence intervals.
The baseline ESPS-2 cohort stratified into low- and
high-risk groups according to the Framingham stroke risk

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 Table 3. Annual Combined Stroke or Vascular Event Rates and RHRs in the European Stroke Prevention Study 2 Trial,
Stratified by Baseline Univariate Risk Factors

Aspirin Plus
Risk Factor No. of Subjects Extended-Release Dipyridamole* Aspirin Alone* RHR (Lower, Upper CL), % P Value
Age ⬎70 y
No 1911 4.6 6.7 31.2 (8.7, 48.2) .01
Yes 1285 13.4 15.1 11.7 (−10.7, 29.6) .28
Sex
Male 1853 7.9 10.2 21.9 (1.7, 38.0) .04
Female 1343 7.8 9.5 17.8 (−8.2, 37.5) .16
Hypertension
No 1277 6.4 7.8 18.7 (−10.9, 40.4) .19
Yes 1919 8.9 11.3 21.0 (2.1, 36.2) .03
Diabetes mellitus
No 2723 7.3 9.2 20.5 (3.2, 34.7) .02
Yes 473 10.9 13.8 20.5 (−17.8, 46.4) .25
Previous MI
No 2915 7.3 9.0 19.4 (2.3, 33.4) .03
Yes 281 13.9 21.3 33.9 (−3.8, 57.9) .07
Atrial fibrillation
No 3000 7.2 9.2 21.7 (5.4, 35.2) .01
Yes 196 20.1 23.2 13.6 (−42.2, 47.5) .57
Any cardiovascular disease
No 730 3.9 5.2 24.3 (−25.8, 54.4) .28
Yes 2466 9.1 11.4 19.9 (3.3, 33.6) .02
Current smoker
No 2411 8.1 9.8 17.1 (−1.4, 32.3) .07
Yes 785 7.3 10.3 29.1 (−1.9, 50.6) .06
Prior stroke or TIA
No 2311 7.5 8.3 9.1 (−13.0, 26.9) .39
Yes 885 8.9 14.2 37.7 (15.5, 54.1) .002
Qualifying event
TIA 776 4.7 6.3 24.8 (−17.3, 51.7) .21
Stroke 2420 9.0 11.1 18.6 (1.4, 32.9) .04

Abbreviations: See Table 2.

*Data are given as annual percentage of subjects in each group who experienced a stroke or vascular event.

Table 4. Annual Stroke Rates and RHRs by Risk Group in Subjects in the European Stroke Prevention Study 2 Trial
Treated With Aspirin Alone or Aspirin Plus Extended-Release Dipyridamole

Aspirin Plus
Risk Group No. of Subjects Extended-Release Dipyridamole* Aspirin Alone* RHR (Lower, Upper CL), % P Value
Framingham stroke risk score
Low 1453 3.4 3.8 12.3 (−30.4, 41.0) .52
High 1743 7.0 10.1 30.2 (10.3, 45.7) .005
SPI-2 risk score
Low 1426 3.2 3.7 11.8 (−32.9, 41.4) .55
Moderate 1471 6.3 9.6 34.3 (12.8, 50.5) .004
High 299 10.9 13.2 17.2 (−39.3, 50.8) .48

Abbreviations: CL, confidence limit; RHR, relative hazard reduction; SPI-2, Stroke Prognostic Instrument II.
*Data are given as annual percentage of subjects in each group who experienced a stroke.

score or the SPI-2 score is shown in Table 4. The an-
nual risk for recurrent stroke among those treated with
aspirin increased from 3.8% in the low-risk group to 10.1%
in the high-risk group for the Framingham score, and from
3.7% to 13.2% for the SPI-2 score. Relative hazard re-
ductions favored the combination of aspirin plus ex-
tended-release dipyridamole in all the subgroups, and were
greatest for the high-risk Framingham group and the mod-
erate-risk SPI-2 subgroup. Numbers in the highest-risk
group, however, were small. Results were similar for the
stroke or vascular events outcome, as shown in Table 5.
COMMENT
Guidelines from the American Heart Association, the
American College of Chest Physicians, and the Euro-
pean Stroke Initiative state that aspirin alone, aspirin plus
extended-release dipyridamole, or clopidogrel is an ac-

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 Table 5. Annual Combined Stroke or Vascular Event Rates and RHRs by Risk Group in Subjects in the European Stroke Prevention
Study 2 Trial Treated With Aspirin Alone or Aspirin Plus Extended-Release Dipyridamole
Aspirin Plus
Risk Group No. of Subjects Extended-Release Dipyridamole*
Framingham stroke risk score
Low 1453 4.1
High 1743 11.4
SPI-2 risk score
Low 1426 4.2
Moderate 1471 9.5
High 299 19.8
Abbreviations: See Table 4.
*Data are given as annual percentage of subjects in each group who experienced a stroke or vascular event.
ceptable option for first-line therapy to prevent recur-
rent stroke.5,7,13 Few data are available regarding how these
recommendations translate into clinical practice and
which factors affect the choice of antiplatelet drugs in pa-
tients with a recent ischemic cerebrovascular event. In a
recent study from the Vienna Stroke Register,14 investi-
gators determined that the most important factor pro-
moting the use of clopidogrel was therapy with aspirin
before the index event. High interhospital variability was
found regarding the use of aspirin plus extended-
release dipyridamole. The relationship between aspirin
and clopidogrel also varied significantly between depart-
ments within a hospital. Thus, the most prominent fac-
tor influencing the use of clopidogrel or aspirin plus ex-
tended-release dipyridamole was the practitioners’
divergent interpretation of the existing evidence. Other
main factors were higher costs (clopidogrel), individual
experiences, and adverse effects (aspirin plus extended-
release dipyridamole).
For the secondary prevention of stroke, alternatives ex-
ist for aspirin. Clopidogrel and aspirin plus extended-
release dipyridamole are more effective than aspirin
alone.9,15,16 Adding dipyridamole to aspirin or substitut-
ing aspirin with clopidogrel is more expensive than aspi-
rin alone in preventing stroke, but these changes in therapy
could be more cost-effective in high-risk patients, if these
patients can be identified.17 It seems that in the long term,
aspirin plus extended-release dipyridamole is more effec-
tive and less costly compared with aspirin alone.18 Thus,
the type of outcome to be prevented, such as recurrent
stroke, MI, or other vascular events, and the relative im-
pact of other concomitant risk factors also enter into the
physician’s decision-making process.
Clinicians should assess the stroke patient’s greatest
risk before determining long-term treatment to prevent
vascular events. The most common vascular event dur-
ing the first few years following a stroke or TIA is a re-
current nonfatal stroke, which often results in signifi-
cant disability and reduction in quality of life.8 Recent
antiplatelet studies, such as the Canadian American Ticlo-
pidine Study, the Ticlopidine Aspirin Stroke Study, the
Clopidogrel vs Aspirin in Patients at Risk of Ischemic
Events trial, and ESPS-2, have clearly demonstrated the
high risk for recurrent stroke, compared with the lower
risk for MI.8 Therefore, from a clinical perspective, treat-
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Aspirin Alone* RHR (Lower, Upper CL), % P Value
5.0 17.4 (−17.8, 42.1) .29
14.3 20.6 (2.7, 35.2) .03
4.9 13.8 (−23.3, 39.7) .42
13.1 27.5 (8.1, 42.7) .008
21.5 7.6 (−37.9, 38.1) .70
ment must focus on preventing subsequent ischemic
strokes. Consequently, the antiplatelet agent that is most
effective for preventing stroke will likely result in the great-
est benefit for patients with a history of stroke or TIA.
Stroke patients often have other vascular conditions,
such as MI or prior stroke, and multiple risk factors, such
as hypertension and diabetes mellitus. When choosing
alternative antiplatelet therapy, the severity of vascular
risk factors can influence the clinician to consider more
aggressive medications. Our post hoc analysis of the
ESPS-2 data shows that the combination of aspirin plus
extended-release dipyridamole is significantly more ef-
fective than aspirin alone in the prevention of recurrent
stroke and stroke or vascular events for various baseline
risk factors. Patients with prior stroke or TIA, those who
experienced a previous MI, and current smokers who used
aspirin plus extended-release dipyridamole had greater
hazard reductions for stroke and stroke or vascular events
than those who took aspirin alone. The reductions ob-
served among patients with prior cardiovascular disease
are noteworthy because some have claimed that aspirin
plus extended-release dipyridamole is less effective among
patients with other cardiovascular conditions.
In addition, aspirin plus extended-release dipyridam-
ole seems to provide greater protection for those patients
with a higher risk for stroke based on predicted stroke prob-
abilities from external stroke models. For diabetes melli-
tus and atrial fibrillation, we did not observe a significant
benefit for aspirin plus extended-release dipyridamole com-
pared with aspirin alone. It is difficult to make any con-
clusions about the atrial fibrillation subgroup because the
numbers of patients randomized were small. Moreover,
the results of the European Atrial Fibrillation Trial that
demonstrated the efficacy of oral anticoagulants led to a
protocol modification and change in practice in many of
the participating ESPS-2 sites during the conduct of the
trial. Analysis of the ESPS-2 data set has shown that the
2-year risk of first stroke for baseline atrial fibrillation sub-
jects was greatest among those treated with placebo (23.4%)
compared with aspirin alone (19.2%) and extended-
release dipyridamole plus aspirin (17.3%).
Limitations of our post hoc analysis exist. The defi-
nitions of the baseline vascular risk factors were based
on data available at randomization into ESPS-2 and may
be skewed because of older classification schemes. The
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use of the Framingham model to stratify patients into low
and high risk may have some limitations because it was
originally designed to predict first stroke. Some of the
variables in the original Framingham model were not
available in the baseline ESPS-2 data set and may have
reduced the accuracy of the stroke risk scores. The model,
however, seemed to competently discriminate the risk
for stroke recurrence among the treatment groups. Al-
though the risk of stroke recurrence increased across the
3 categories of the SPI-2, it was originally designed to pre-
dict stroke or any death. The lower efficacy of extended-
release dipyridamole plus aspirin vs aspirin alone among
the highest-risk group may reflect the lower impact of
antiplatelet agents on any death after stroke.
This post hoc analysis of ESPS-2 data adds to the grow-
ing information supporting the efficacy of combination
therapy with antiplatelet agents, particularly in higher-
risk stroke patients. Aspirin plus extended-release di-
pyridamole is more effective than aspirin alone at pre-
venting stroke, and the difference in efficacy increases
in higher-risk patients. The baseline vascular risk for the
stroke patient is one important consideration when mak-
ing decisions regarding the most effective antiplatelet regi-
men to prevent a stroke.
Accepted for Publication: July 15, 2004.
Correspondence: Ralph L. Sacco, MS, MD, Departments
of Neurology and Epidemiology, College of Physicians and
Surgeons and the Mailman School of Public Health, Co-
lumbia University, Neurological Institute, 710 W 168th
St, New York, NY 10032 (RLS1@columbia.edu).
Author Contributions: Study concept and design: Sacco
and Diener. Acquisition of data: Sivenius and Diener. Analy-
sis and interpretation of data: Sacco and Diener. Drafting
of the manuscript: Sacco and Diener. Critical revision of
the manuscript for important intellectual content: Sacco, Sive-
nius, and Diener. Statistical analysis: Sacco. Obtained
funding: Sacco. Administrative, technical, and material sup-
port: Sacco and Diener. Study supervision: Sacco.
Funding/Support: This study was supported by Boeh-
ringer Ingelheim, Ridgefield, Conn.
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