AHA Project: PSYCHO-SOCIAL/DEPRESSION
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
Subgroup Analyses of
Clinical Endpoints in
Women
Notes
Berkman
2003
RCT
N overall:
2,481
Secondary
prevention
Primary study outcome(s):
Composite primary end point
of death or recurrent MI
N women:
1,084
Status post MI
1) Cognitive
behavior therapy
(median of 11
individual sessions
over 6 mos, plus
group therapy
when feasible)
(n = 1,238)
1) Composite outcome(s):
Some evidence of treatment
group-by-sex interaction.
Data provided in figure,
showing increased risk of
death/MI with intervention in
women (HR approx 1.22,
95% CI approx 0.95-1.55).
Unadjusted p = 0.03,
adjusted p = 0.20
Of intervention
group, 21% on
SSRIs by end of
follow up, 14.6%
of usual care
group on SSRIs
by end of f/u
ENRICHD
Mean age:
61
Age range:
SD 12.5
2) SSRIs
(sertraline starting
50 mg/d titrated to
max 200 mg/d as
determined by
treating
psychiatrist)
Alternative meds
(another SSRI or
nortryptiline) used if
patients did not
respond to
sertraline or were
unable to tolerate
(n = 260)
% Diabetics:
33
% Caucasian
66
Clinical endpoints of interest:
1) Composite outcome(s):
Usual care: 300
Intervention: 299
HR 1.01 (95% CI 0.86-1.18)
2) Heart attack/MI:
Usual care: 170
Intervention: 168
HR 0.90 (95% CI 0.71-1.14)
3) Stroke (hemorrhagic,
non-hemorrhagic, TIA):
NR
4) Revascularization
procedure (PCI, bypass):
Usual care: 230
Intervention: 216
HR 0.94 (0.78-1.14)
5) Death/mortality:
Usual care: 172
Intervention 168
HR 0.98 (0.79-1.21)
Pts followed for
at least 18 mos
(mean 29 mos)
2) Heart attack/MI:
NR
3) Stroke (hemorrhagic,
non-hemorrhagic, TIA):
NR
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality:
NR
6) CHF:
NR
6) CHF:
NR
7) PVD:
NR
Blumentha
l
2004
RCT
N overall:
2,078
Secondary
prevention
N women:
Status post MI
1) self-reported
physical exercise
(exercisers)
(n=982)
Primary study outcome(s):
-Death
-recurrent MI
1 of 14
None reported
Pts followed for
at least 4 yrs
(mean 23 mos)
Study
Design
ENRICHD
No. of
Patients
Patient
Population
Interventions
Outcomes
Mean age:
60
Depressed
(DSM-IV
criteria)
2) non-exercisers
(n=1,096)
Clinical endpoints of interest:
1) Composite endpoint:
NR
Age range:
60.4±12.3
Low perceived
social support
903
Subgroup Analyses of
Clinical Endpoints in
Women
Notes
None reported
22.6% of
intervention
group, and
14.1% of usual
care group on
antidepressant
during the first 6
mos
2) Heart attack/MI: 179 pts
non-exercisers: 10.5%
exercisers : 6.5%
HR 0.72 (95% CI 0.52-0.99)
p=0.044
% Diabetics:
32.9
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
% Caucasian
NR
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality: 187 pts
non-exercisers: 12.0%
exercisers : 5.7%
HR 0.62 (95% CI 0.44-0.86)
p=0.004
6) CHF:
NR
7) PVD:
NR
Carney
2004
ENRICHD
RCT
N overall:
858
Secondary
prevention
N women:
431
Status post MI,
pts who
survived 6 mos
after after
index MI and
completed 6
mo depression
assessment
Mean age:
59
Age range:
NR
1) Cognitive
behavior therapy
(CBT) (median of
11 individual
sessions over 6
mos, plus group
therapy when
feasible)
Or CBT + SSRIs
(sertraline starting
50 mg/d titrated to
max 200 mg/d as
Primary study outcome(s):
Death from any cause (6
mos after randomization)
Clinical endpoints of interest:
1) Composite outcome(s):
NR
2) Heart attack/MI:
NR
3) Stroke (e.g. hemorrhagic,
2 of 14
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
% Diabetics:
34
Depressed
(DSM-IV
criteria)
determined by
treating
psychiatrist, for 12
mos) Alternative
meds (another
SSRI or
nortryptiline) used if
pts did not respond
to sertraline or
were unable to
tolerate (n = 449)
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
%Caucasian:
67
2) Usual care
(n=409)
Subgroup Analyses of
Clinical Endpoints in
Women
Notes
Not applicable (no women)
10 yrs f/u
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality:
CBT: 49
usual care:52
HR 0.84 (95% CI 0.56,1.23)
p=0.37
6) CHF:
NR
7) PVD:
NR
Eng
2002
Cohort
study
N overall:
28,369 men
Primary
prevention
N women:
0
Healthy
professionals
stratified in 4
level of social
integration
based on the
BerkmanSyme social
network index
Mean age:
55
Age range:
42-77
% Diabetics:
2.4
% Caucasian
NR
1) low social
integration
(n=1,687)
2): medium social
integration
(n=6,798)
3): medium-high
social integration
(n=5,329)
4) high social
integration
(n=14,555)
Primary study outcome(s):
-All-cause mortality
-Cardiovascular disease
mortality (coronary heart
disease and stroke)
-Cancer mortality
-mortality due to external
cause of injury
-mortality from all others
causes
Clinical endpoints of interest:
1) Composite outcome(s):
NR
2) Heart attack/MI:
618
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
3 of 14
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality:
Total mortality:1,365
Group IV is reference group
-Multivariate RR, p=0.009
I vs IV
RR 1.20 (95%CI 0.97-1.48)
II vs IV
RR 1.18 (95%CI 1.03-1.34)
III vs IV
RR 0.97 (95% CI 0.83-1.13)
-Age adjusted RR, p<0.001
I vs IV
RR 1.49 (95%CI 1.23-1.82)
II vs IV
RR 1.28 (95%CI 1.13-1.45)
III vs IV
RR 1.00 (95% CI 0.86-1.16)
Cardiovascular death: 302
Group IV is reference group
-Multivariate RR, p=0.11
I vs IV
RR 1.37 (95%CI 0.91-2.08)
II vs IV
RR 1.16 (95%CI 0.88-1.52)
III vs IV
RR 1.07 (95% CI 0.79-1.44)
-Age adjusted RR, p=0.03
I vs IV
RR 1.53 (95%CI 1.02-2.29)
II vs IV
RR 1.21 (95%CI 0.93-1.58)
III vs IV
RR 1.04 (95% CI 0.77-1.41)
6) CHF:
NR
4 of 14
Subgroup Analyses of
Clinical Endpoints in
Women
Notes
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
Subgroup Analyses of
Clinical Endpoints in
Women
Notes
None reported
Data gathered at
baseline and 16
wks
7) PVD:
NR
Glassman
2002
RCT
N overall:
369
Secondary
prevention
N women:
135
MI (74%) or
unstable
angina (26%)
Mean age:
57
Age range:
SD 11.1
% Diabetics:
31
% Caucasian
74 sertraline
79 placebo
1) Sertraline 50200 mg QD
(n = 186)
Primary study outcome(s):
Change from baseline in LV
ejection fraction
2) Placebo
(n = 183)
Clinical endpoints of interest:
1) Composite outcome(s):
Death and urgent CV rehospitalizations
Sertraline: 32
Placebo: 41
RR 0.77 (95% CI, 0.51-1.16)
2) Heart attack/MI:
Sertraline: 5
Placebo: 7
RR 0.70 (0.23-2.16)
3) Stroke (hemorrhagic,
non-hemorrhagic, TIA):
Sertraline: 2
Placebo: 2
RR 0.98 (0.14-6.93)
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality:
Sertraline: 2
Placebo: 5
RR 0.39 (0.08-1.39)
6) CHF:
Sertraline: 5
Placebo: 7
RR 0.70 (0.23-2.16)
7) PVD:
NR
5 of 14
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
Subgroup Analyses of
Clinical Endpoints in
Women
Notes
Jenkinson
1993
Cohort
study
N overall:
1,376
Secondary
prevention
Self-reported
I) Low social
isolation
(n= 1,196)
Primary study outcome(s):
Survival after MI
None reported
Pt f/u median of
3 yrs.
N women:
303
Mean age:
NR
II) High social
isolation
(n= 132)
Age range:
60-75+
3) Not known
(n=48)
Clinical endpoints of interest:
1) Composite outcome(s):
survival after 6 mos:
Low social: 94%
High social: 89%
survival after 12 mos
Low social 92%
High social 85%
% Diabetics:
NR
survival after 36 mos
Low social 83%
High social 77%, P=0.065
% Caucasian
NR
2) Heart attack/MI:
NR
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality:
NR
6) CHF:
NR
7) PVD:
NR
Monster
2004
Cohort
study
N overall:
8,887 cases
Cases:
88,862
Mixed
1) SSRIs
(serotonin reuptake
inhibitors)
Case n=57
Primary study outcome(s):
Hospitalization for
myocardial infarction
6 of 14
None reported
Study
Design
No. of
Patients
first time
hospitali
zation
for MI
Cases
and
controls
stratified
based
on a
previous
history of
vascular
disease
(CVD)
Interventions
Outcomes
controls
Control n=882
N women:
No history of
CVD
Cases 1,878
Controls
29,281
2) nonselective
SSRIs
Case n=34
Control n=451
Clinical endpoints of interest:
1) Composite outcome(s):
NR
History of
CVD
Cases 1,486
Controls
4,357
Mean age:
NR
No history of
CVD
Cases 69
Controls 67
History of
CVD
Cases 75
Controls 72
Age range:
NR
Patient
Population
3) other
Case n=38
Control n=521
2) Heart attack/MI:
No history of CVD
-SSRIs
OR 0.90( 95%CI 0.67-1.19)
-nonselective SSRIs
OR 1.05 ( 95%CI 0.72-1.52)
-other
OR 1.09( 95%CI 0.76-1.55)
History of CVD
-SSRIs
OR 0.85 ( 95%CI 0.62-1.16)
-nonselective SSRIs
OR 0.83 ( 95%CI 0.50-1.38)
-other
OR 0.55 ( 95%CI 0.31-0.97)
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
% Diabetics:
4) Revascularization
procedure (PCI, bypass):
NR
No history of
CVD
Cases 10.2
Controls 4.2
5) Death/mortality:
NR
History of
CVD
Cases 18.9
Controls 12.1
6) CHF:
NR
7) PVD:
NR
7 of 14
Subgroup Analyses of
Clinical Endpoints in
Women
Notes
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
Subgroup Analyses of
Clinical Endpoints in
Women
Mixed
Social network
scores were
derived from a
questionnaire
completed by
Japanese men in
Hawaii. The men
were divded into
quartiles of
I) conceptual social
network score
II) factor-derived
social network
score
Primary study outcome(s):
total CHD, fatal MI, non-fatal
MI, angina
Not applicable (no women)
% Caucasian
NR
Reed
1983
Cohort
study
N overall:
4,653
N women:
0
Mean age:
NR
Age range:
NR
% Diabetics:
NR
%Caucasian:
0
Clinical endpoints of interest:
1) Composite outcome(s):
Total CHD (rates/1,000):
I) conceptual
1: lowest score n=58
2: n= 51
3: n=44
4: highest score n=51
II) factor-derived
1: lowest score n=58
2:n=50
3: n=51
4: n=45
p= 0.03
2) Heart attack/MI:
(rates/1000)
1) conceptual
1: lowest score n=42
2: n=41
3: n=36
4: highest score n=39
II) factor-derived
1: lowest score n=46
2: n= 41
3: n= 37
4: n=35
p=0.04
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
8 of 14
Notes
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
Subgroup Analyses of
Clinical Endpoints in
Women
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality:
NR
6) CHF:
NR
7) PVD:
NR
Sauer
2003
Casecontrol
study
N overall:
Cases 1,080
Controls
4,256
N women:
Controls
2,505
Mean age:
NR
Age range:
40-75
% Diabetics:
Controls: 7
% Caucasian
Controls: 81
Primary
prevention
1) SSRIs users
(n=328)
Primary study outcome(s):
Myocardial infarction
Case: pts with
first MI
2) non
antidepressant
(AD) users
(n=3,928)
Clinical endpoints of interest:
1) Composite outcome(s):
NR
2) Heart attack/MI:
SSRIs vs other AD
OR 0.51 (95%CI 0.29-0.90)
p=0.02
SSRIs vs non AD
OR 0.72 (95%CI 0.49-1.05)
p=0.09
SSRIs high affinity vs non
AD
OR 0.59 (95%CI 0.39-0.91)
p=0.02
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
4) Revascularization
procedure (PCI, bypass):
NR
9 of 14
None reported
Notes
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
Subgroup Analyses of
Clinical Endpoints in
Women
5) Death/mortality:
NR
6) CHF:
NR
7) PVD:
NR
Schlienger
2004
Casecontrol
study
N overall:
Cases 8,688
Controls
33,923
N women:
Cases 3,225
Controls
12,613
Mean age:
70
Age range:
<90
% Diabetics:
Cases 13.6
Controls 6.7
% Caucasian
NR
Primary
prevention
Case: pts with
first MI
1) SSRIs users
cases n=235
controls n=899
2) non-SSRIs
users
cases n=1,129
controls n=3,867
3) other
antidepressant
(AD) users
cases n=440
controls n=1,532
4) not users of any
AD
cases n=6,884
controls n=27,652
Primary study outcome(s):
MI
1) Composite outcome(s):
NR
Clinical endpoints of interest:
1) Composite outcome(s):
NR
2) Heart attack/MI:
SSRIs vs not users
-women
RR 0.92 (95%CI 0.67-1.28)
p=0.62
2) Heart attack/MI:
SSRIs vs not users
OR 0.63 (95%CI 0.43-0.91)
p=0.02
Non-SSRIs vs not users
OR 0.92 (95%CI 0.77-1.09)
p=0.32
Other AD vs not users
OR 0.59 (95%CI 0.29-1.20)
p=0.14
Stratified by age
-Age < 70
SSRIs vs not users
OR 0.55 (95%CI 0.39-0.79)
p=0.001
-Age >70
SSRIs vs not users
OR 0.85 (95%CI 0.62-1.17)
p=0.32
Stratified by sex
-men
SSRIs vs not users
10 of 14
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality:
NR
6) CHF:
NR
7) PVD:
NR
Notes
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
Subgroup Analyses of
Clinical Endpoints in
Women
Notes
1) Composite outcome(s):
Primary outcome:
White women:
HR 1.14 (95% CI 0.85-1.52)
p=0.39
Pts followed for
max of 4.5 yrs
(mean 2.4 yrs)
RR 0.53 (95%CI 0.38-0.76)
p<0.0005
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality:
NR
6) CHF:
NR
7) PVD:
NR
Schneider
man
2004
Post-hoc
analysis
of RCT
on sex
and
ethnic
minority
subgrou
p
N overall:
2,481
Secondary
prevention
N women:
1,084
White
women:674
Minority
women:410
Pts with major
and minor
depression
and/or low
perceived
social support
ENRICH
D
Mean age:
White
women:674
Minority
women:410
Age range:
NR
% Diabetics:
White
women: 35
1) Cognitive
behavior therapy
(CBT)
white male
n=497
minority male
n=209
white female
n=332
minority female
n=200
2) usual care
white male
n=476
minority male
n=215
white female
n=342
minority female
n=210
Primary study outcome(s):
Total mortality or recurrent
non fatal MI
Secondary outcomes:
Cardiac mortality or
recurrent non fatal MI
Clinical endpoints of interest:
1) Composite outcome(s):
Primary outcome:
White men:
HR 0.80 (95% CI 0.61-1.05)
p=0.10
Minority women:
HR 1.35 (95% CI 0.92- 1.97)
p=0.12
Secondary outcome:
White women:
HR 1.14 (95% CI 0.81-1.61)
p=0.44
Minority men:
HR 0.99 (95% CI 0.66-1.47)
p= 0.94
Minority women:
HR 1.07 (95% CI 0.69- 1.66)
p=0.75
Secondary outcome:
White men:
HR 0.63 (95% CI 0.46-0.87)
2) Heart attack/MI:
NR
11 of 14
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
p= 0.004
Minority
women:50
Minority men:
HR 1.18 (95% CI 0.74-1.88)
p= 0.49
% Caucasian
(see above)
2) Heart attack/MI:
NR
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
4) Revascularization
procedure (PCI, bypass):
NR
Subgroup Analyses of
Clinical Endpoints in
Women
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
Notes
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality:
NR
6) CHF:
NR
7) PVD:
NR
5) Death/mortality:
NR
6) CHF:
NR
7) PVD:
NR
Taylor
2005
ENRICHD
RCT
Observat
ional
seconda
ry
analysis
N overall:
1,834
N women:
849
Mean age:
59
1) SSRIs:
59±12.6
2) nonSSRIs:
58±11.2
3) No AD
users:
61± 12.6
Secondary
prevention
1) SSRIs
(serotonin reuptake
inhibitors)
(n=301)
2) non-SSRIs
(Tricyclic)
(n=1,388)
3) No AD users
(n=145)
Primary study outcome(s):
Recurrent MI or death from
any cause
Secondary outcomes:
Revascularization procedure
and cardiovascular
hospitalization
Clinical endpoints of interest:
1) Composite outcome(s):
primary outcome:
AD users (SSRI and nonSSRI) vs No AD users
HR 0.61 (95% CI 0.45- 0.84)
SSRI vs No AD users
12 of 14
None reported
F/u
Study
Design
No. of
Patients
Patient
Population
Interventions
Outcomes
HR 0.57 (95% CI 0.38- 0.84)
Age range:
NR
% Diabetics:
1)SSRIs:38
2)non-SSRIs:
37
3)No AD
users: 34
% Caucasian
NR
Non-SSRI vs No AD users
HR 0.72 (95% CI 0.44- 1.18)
2) Heart attack/MI:
AD users (SSRI and nonSSRI) vs No AD users
HR 0.57 (95% CI 0.38- 0.87)
SSRI vs No AD users
HR 0.53 (95% CI 0.32- 0.90)
Non-SSRI vs No AD users
HR 0.73 (95% CI 0.38- 1.38)
3) Stroke (e.g. hemorrhagic,
non-hemorrhagic, TIA, fatal
or nonfatal):
NR
4) Revascularization
procedure (PCI, bypass):
NR
5) Death/mortality:
AD users (SSRI and nonSSRI) vs No AD users
HR 0.63 (95% CI 0.43- 0.93)
SSRI vs No AD users
HR 0.59 (95% CI 0.37- 0.96)
Non-SSRI vs No AD users
HR 0.64 (95% CI 0.34- 1.22)
6) CHF:
NR
7) PVD:
NR
13 of 14
Subgroup Analyses of
Clinical Endpoints in
Women
Notes
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Sauer, W. H., Berlin, J. A., and Kimmel, S. E. Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial
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