APPENDIX
Do observational studies using propensity score methods agree with randomized
trials? A systematic comparison of studies on acute coronary syndromes
1
Issa J. Dahabreh MD MS, 2Radley C. Sheldrick PhD, 3,4Jessica K. Paulus ScD, 1Mei
Chung PhD MPH, 5Vasileia Varvarigou MD, 6Haseeb Jafri MD, 7,8Jeremy A. Rassen
ScD, 1Thomas A. Trikalinos MD PhD, 1,9Georgios D. Kitsios MD PhD
1
Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts
Medical Center, Boston, MA
2
Division of Developmental-Behavioral Pediatrics, Department of Pediatrics, Floating Hospital for
Children, Tufts Medical Center, Boston, MA
3
Tufts Clinical and Translational Science Institute, Tufts University, Medford, MA
4
Department of Epidemiology, Harvard School of Public Health, Boston, MA
5
Department of Environmental and Occupational Medicine & Epidemiology, Harvard School of Public
Health, Boston, MA
6
Division of Cardiology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine,
Baltimore, MD
7
Division of Pharmacoepidemiology & Pharmacoeconomics, Department of Medicine, Brigham &
Women’s Hospital, Boston, MA
8
Harvard Medical School, Boston, MA
9
Division of Internal Medicine, Lahey Clinic Medical Center, Burlington, MA
1
Appendix Document: Detailed research methods.
Compiling a database of PS-based observational studies
This study was based on a pre-specified protocol. We conducted a Medline search to
identify studies using propensity score (PS) methods to obtain estimates of treatment
efficacy for therapeutic interventions administered to patients with acute coronary
syndromes (ACS). ACS was defined as acute myocardial infarction (AMI, including both
ST-elevation myocardial infarction, STEMI, and non-ST-elevation myocardial infarction,
NSTEMI) or unstable angina (UA). We accepted the specific disease definitions of the
primary studies. We used a search strategy developed in Ovid Medline (see Box 1,
below). To increase the specificity of the search we limited our searches for studies using
PS methods to journals publishing primary clinical research studies and selected the top 8
cardiology journals (Circulation, Journal of the American College of Cardiology,
American Journal of Cardiology, Annals of Thoracic Surgery, European Heart Journal,
American Heart Journal, Heart, International Journal of Cardiology) and the top 4
general medical journals (New England journal of Medicine, Lancet, Journal of the
American Medical Association, British Medical Journal), as defined by 2-year impact
factor in 2009 (Institute of Scientific Information, Thomson Reuters, Philadelphia, PA).
We screened titles and abstracts to identify studies enrolling patients with an established
diagnosis of ACS that used propensity scores to obtain estimates of the efficacy of
competing therapeutic interventions. We selected abstract that explicitly reported the
inclusion of patients with ACS, i.e. we excluded abstracts that did not specify the patient
population included. We randomly sampled 50 of the abstracts excluded because their
population was not defined as ACS; of these, none would have been considered eligible
2
for our analyses (they included >20% of non-ACS patients, did not build separate
propensity score models or did not report estimates of the treatment effect based on
propensity score models built within the ACS subgroup). Because abstract reporting of
outcome information is often incomplete, we did not require that mortality was identified
as an outcome at the abstract-screening level.
Potentially eligible studies were reviewed in full text to determine eligibility by two
reviewers (IJD and GK) and discrepancies were resolved by consensus. Eligible studies
had to have an observational design, enroll patients with a diagnosis of ACS, and use
propensity score methods to obtain estimates for treatment effects of therapeutic
interventions on mortality. We considered studies reporting on both short-term (typically
within 30 days of ACS diagnosis) and long term (>30 days following ACS diagnosis)
mortality. Other outcomes were not considered to limit the potential of outcome
misclassification.
From each eligible study a single reviewer extracted the following information: first
author name, year of publication, population of interest, therapeutic intervention assessed,
comparator (no treatment or alternative treatment) assessed, and mortality outcomes
assessed (short term and long term).
Matching observational studies to RCTs
Two reviewers (IJD and GK) independently attempted to match observational studies
using PS methods to RCTs using a structured approach (see below). For each
observational study the reviewers attempted to identify randomized trials addressing the
same intervention and comparator for the same population of patients.
3
a. For interventions and comparators, matching of PS-based studies and RCTs
required that studies examined the same pharmaceutical or invasive (nonpharmacological) interventions applied in the same clinical setting (for example,
for an observational study reporting the comparison of primary PCI with and
without abciximab we required a RCT that examined primary PCI with abciximab
versus placebo or no treatment; a RCT that examined the use of multiple IIb/IIIa
inhibitors but not exclusively abciximab was not to be considered as an
appropriate match).
b. For populations, matching was based on the examination of the same subtype of
ACS (STEMI vs. NSTEMI vs. mixed) in both study designs (e.g. both
observational studies and RCTs examining STEMI patients). For studies enrolling
only one subtype of ACS, when no “perfect” match was identified, we used an
operational threshold of at least 80% similarity in the type of ACS for each of the
compared populations.
c. Additional demographic or comorbidity characteristics of the examined
populations were considered in the matching process in cases where they
represent a selection criterion of the examined population (for example, for
observational studies that examined the effects of a treatment in octogenarians, we
searched for randomized studies that had included similarly aged patient
populations; or for observational studies that included patients with ACS and
chronic kidney disease, we searched for RCTs that specifically included ACS
patients based on the presence of chronic kidney disease and we will then aimed
to match the two study designs based on the severity of kidney disease).
4
d. With regards to the comparability of study outcomes, RCTs will be considered
only if they report on the same mortality outcome (operationally classified as
short or long term) as the corresponding observational study using PS methods.
To identify potential “matches” for each PS based study we used the following
structured approach:
a. We conducted searches in the Cochrane Database of Systematic Reviews to
identify reviews published or updated after 2008 (to ensure the results were
current) investigating the same population, treatments and outcomes as the
observational studies using PS methods.
b. When such a review was not available we performed Medline searches using
terms relevant to systematic reviews and the intervention of interest. We also
examined the recently updated, evidence-based guidelines of the American Heart
Association/American College of Cardiologists (AHA/ACC) to identify eligible
trials (that were considered relevant to the same population and intervention
reported in the observational studies) and we also evaluated the relevant chapters
of a recent compendium of therapeutics (Washington Manual of Medical
Therapeutics) for citations of eligible RCTs.
c. We then performed targeted Medline searches (with key words relevant to the
specific intervention, population and randomized trial design) for eligible primary
RCTs.
d. When no RCT investigating the same comparison (population, intervention and
outcome) as the observational study, we considered using treatment effect
5
estimates for specific subgroups of interest from individual patient data metaanalyses of RCTs (when such meta-analyses were identified by the literature
searches described above).
e. As a final matching step, we considered subgroups of interest from single RCTs,
provided that these RCTs are large enough to provide precise treatment estimates
(at least 1000 patients).
f. As one mechanism to verify our matches (as well as a potential source of
matching RCTs when none of the sources described above led to the identification
of an adequately similar RCT), we also consulted the reference lists of the
observational studies study to identify any RCTs that the observational study’s
authors had considered sufficiently similar to their investigation (in terms of
populations enrolled and interventions assessed).
We searched these sources successively: we proceeded to a step only if at least one
matching RCT was not identified at the previous step (a to f). When a relevant metaanalysis was identified (steps a and b) all included trials were retrieved and examined in
full text for potential matches. When individual trials (or subgroups of trial) were
considered (steps c and e) all trials identified through our searches were considered. In
cases when an observational study using propensity score methods could be matched to
multiple meta-analyses, we considered the largest meta-analysis (i.e. the one including
more trials) as the primary source of matching RCTs (but we also verified that all RCTs
from previous reviews had been included in the latest one to account for potential
6
differences in selection criteria or search strategies among systematic reviews on the
same topic).
We realize that there is inherent subjectivity in identifying observational studies and
RCTs that were sufficiently similar with regards to their populations and interventions.
This is an inherent imitation to all empirical investigations similar to ours. To limit the
potential for bias, two investigators (both physicians with training in epidemiological and
systematic review methods, IJD and GK) independently attempted to match observational
studies with RCTs. Given the complexity of the process, agreement was not assessed
formally and all decisions were reached by consensus. Another reviewer (HJ) verified all
the matches of observational studies to RCTs after a provisional matched set had been
generated in order to finalize the dataset (used for data extraction and analyses).
Assessing the validity of PS-based analyses
To assess the quality of the observational studies using propensity score methods that
were successfully matched to at least one RCT, we extracted information on previously
established criteria relevant to the study design and statistical analyses of these studies
(Box 2). This extraction was performed by a single reviewer (CRS, JKP, MC, VV) and
verified by another reviewer (IJD or GK).
7
Box 1: Search strategy for identifying observational studies using propensity score
methods.
Searches
Results
1
propensity.mp.
17264
2
"new england journal of medicine".jn.
61713
3
lancet.jn.
117312
4
"journal of the american medical association".jn.
7831
5
british medical journal.jn.
41373
6
"annals of internal medicine".jn.
25522
7
circulation.jn.
34997
8
"journal of the american college of cardiology".jn.
16940
9
"american journal of cardiology".jn.
30523
10 "annals of thoracic surgery".jn.
25135
11 european heart journal.jn.
11110
12 american heart journal.jn.
20548
13 heart.jn.
6655
14 "international journal of cardiology".jn.
10124
15 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14
409783
16 1 and 15
515
17 myocardial infarction.mp. or exp Myocardial Infarction/
160416
18 Coronary artery disease.mp. or exp Coronary Artery Disease/
61912
19 Coronary disease.mp. or exp Coronary Disease/
162457
20 heart disease.mp. or exp Heart Diseases/
784888
21 17 or 18 or 19 or 20
805001
22 18 and 21
599
8
Box 2: Information extracted from observational studies using propensity score methods.









Author, year, journal of publication
Population
o STEMI
o NSTEMI
o UA
o If mixed ACS: % NSTEMI/UA
Intervention, Comparator
Outcome: (description, binary vs. time-to-event)
o Short term mortality (≤30d)
o Long term mortality (>30d)
Design:
o Prospective
o Recruitment from RCT population
o Dataset source (administrative vs. clinical)
o Sample size (overall / intervention / comparator groups)
Multivariate outcome model without PS
o Logistic regression
o Cox-model
o Other (detailed description)
o N of variables in final model
o N of outcomes per variable
Propensity score estimation
o Logistic regression
o Other generalized model
o N of variables in model
o N of outcomes per variable
o Reporting of included variables
o Selection of included variables

Reported vs. NR

If reported

Literature review for predictors of exposure

Expert knowledge of predictors of exposure+ and outcome

Predictors of exposure from prior studies

Stepwise selection

Examination of imbalances between treated and untreated groups
o AUC of PS
Use of Propensity score:
o MATCHING: Y/N

Process for formation of matched pairs reported

Ratio of matching: (e.g. 1:2, 1:1)

Assessment of balance between matched pairs

N of matched pairs

N of unmatched treated

N of unmatched untreated

Did the method used to estimate the treatment effect take into account the paired
nature of data?
o STRATIFICATION

N of strata

Assessment of balance following stratification

Method for estimation of overall Tx effect
o REGRESSION ADJUSTMENT WITH PS
o Specification of PS variable functional form in model
o IPW WITH PS
Detailed extraction of results based on the underlying analysis
o PS-matched analysis, effect size reported or calculated, p-value
o PS-stratified analysis, effect size reported or calculated, p-value
o PS-adjusted analysis, effect size reported or calculated, p-value
o PS-weighted analysis, effect size reported or calculated, p-value
o MV model without PS, effect size reported or calculated, p-value
9
Appendix Figure 1: A. Relative risks from randomized controlled trials (white circles)
and observational studies using propensity score methods (red squares) reporting on
short-term mortality, stratified by topic. B. Relative risks from randomized controlled
trials (white circles) and observational studies using propensity score methods (red
squares) reporting on short-term mortality, stratified by topic. Extending lines depict 95%
confidence intervals for the estimates. Arrows indicate lower or upper bounds of
confidence intervals that were outside the plotted range of values.
10
Appendix Figure 2: Relative risks from observational studies using both propensity
score methods (red squares) and simple regression adjustments (black squares). Estimates
from analyses using propensity score methods are depicted as Extending lines depict 95%
confidence intervals for the estimates.
11
Appendix Table 1: Detailed characteristics of observational studies using propensity score methods and matched randomized
controlled trials investigating the same interventions and patient populations.
Treatment
Publication
Population
information
Short-term mortality - Pharmacological interventions
Abciximab timing in pPCI
Dudek, 2008, Am
STEMI planned to be
Heart J1
treated with primary PCI
IIb/IIIa inhibitors (NSTE-ACS)
Statins timing (AMI)
Intervention
Comparator
Outcome
(Mortality)
Design
early abciximab administration
(before admission to cathlab for
primary PCI)
late abciximab administration
(periprocedural)
30 d
PS
Maioli (RELAxAMI), 2007, JACC2
STEMI planned to be
treated with primary PCI
early abciximab administration
(before admission to cathlab for
primary PCI)
late abciximab administration
(periprocedural, after
angiography)
30 d
RCT
Zorman, 2002, Am
J Cardiol3
STEMI planned to be
treated with primary PCI
early abciximab administration
(before admission to cathlab for
primary PCI)
late abciximab administration
(periprocedural, after
angiography)
in-hospital
RCT
Gabriel (ERAMI),
2006, Catheter
Cardiovasc Interv4
STEMI planned to be
treated with primary PCI
early abciximab administration
(before admission to cathlab for
primary PCI)
late abciximab administration
(periprocedural, after
angiography)
30 d
RCT
Peterson, 2003,
JACC5
PURSUIT, 1998,
NEJM6
GUSTO IV-ACS,
2001, Lancet7
Fonarow, 2005, Am
J Cardiol8
NSTEMI
IIb/IIIa inhibitor within 24h of
presentation
eptifibatide within 24h of
presentation
abciximab within 24h of
presenting with symptoms
statin initiation within first 24h of
admission
no IIb/IIIa within 24h of
presentation
placebo
in-hospital
PS
7d
RCT
placebo
7d
RCT
no statin within first 24h of
admission
in-hospital
PS
NSTE-ACS
NSTE-ACS
AMI (73% NSTEMI)
12
Treatment
Publication
Population
information
Sakamoto, 2006,
AMI (11% NSTEMI)
Am J Cardiol9
Macin, 2005, Am
ACS (NR% NSTE-ACS)
Heart J10
Short-term mortality – non-pharmacological interventions
pPCI (shock)
Babaev, 2005,
STEMI with shock
JAMA11
pPCI (elderly)
Invasive strategy timing
(NSTE-ACS)
Intervention
Comparator
Design
no statin
Outcome
(Mortality)
7d
statin initiation within 96h of
symptom onset
statin initiation within 48h of
symptom onset
no statin
30 d
RCT
primary PCI
medical management
in-hospital
PS
RCT
Urban, 1999, Eur
Heart J12
AMI with shock (20%
NSTEMI)
early angiography followed by
revascularization when indicated
(84% received PCI)
initial medical management
30 d
RCT
Mehta, 2004, Am
Heart J13
de Boer, 2002,
JACC14
Bueno (TRIANA),
2011, Eur Heart J15
SENIOR PAMI,
2005, unpublished
Shavelle, 2002, Am
Heart J16
Montalescot
(ABOARD), 2009,
JAMA17
Neumann (ISARCOOL), 2003,
JAMA18
van'tHof (ELISA),
2003, Eur Heart J19
STEMI, >70 years
primary PCI
thrombolysis
in-hospital
PS
STEMI, >75 years
primary PCI
thrombolysis
in-hospital
RCT
STEMI, >75 years
primary PCI
thrombolysis
30 d
RCT
STEMI, >70 years
primary PCI
thrombolysis
30 d
RCT
NSTEMI with ST-segment
depression
NSTE-ACS
early angiography (<6h)
early conservative therapy
in-hospital
PS
immediate angiography
delayed angiography for next
working day
30 d
RCT
NSTE-ACS
early angiography (<6h)
delayed angiography (>3 d)
30 d
RCT
NSTE-ACS
early angiography (<12h)
delayed angiography (>24h)
30 d
RCT
13
Treatment
Invasive strategy (NSTE-ACS)
Publication
information
Bhatt, 2004,
JAMA20
Population
Intervention
Comparator
NSTE-ACS
angiography within 48h of
presentation
early conservative strategy (no
angiography within 48 h of
presentation)
TIMI IIIB, 1994,
Circulation21
NSTE-ACS
FRISC II, 1999,
Lancet22
NSTE-ACS
Spacek (VINO),
2002, Eur Heart J23
NSTEMI
Cannon (TACTICSTIMI 18), 2001,
NEJM24
NSTE-ACS
Fox (RITA 3), 2002,
Lancet25
NSTE-ACS
angiography within 48h of
randomization (followed by
revascularization, when
indicated)
angiography within 1 wk of
randomization (followed by
revascularization, when
indicated)
angiography within 24h of
symptom onset (followed by
revascularization, when
indicated)
angiography within 48h of
randomization (followed by
revascularization, when
indicated)
angiography within 3 d of
randomization
Boden
(VANQWISH),
1998, NEJM26
NSTEMI
angiography within 3 d of
symptom onset (followed by
revascularization, when
indicated)
AMI (54% NSTEMI)
Long-term mortality - Pharmacological interventions
ACEi (AMI)
Milonas, 2010, Am
J Cardiol27
Ambrosioni
(SMILE), 1995,
NEJM28
Kleber (ECCE),
Outcome
(Mortality)
in-hospital
Design
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results)
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results)
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results)
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results)
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results)
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results)
in-hospital
RCT
in-hospital
RCT
in-hospital
RCT
in-hospital
RCT
in-hospital
RCT
in-hospital
RCT
no ACE inhibitor treatment at
discharge
placebo
12 mo
PS
anterior AMI (34%
NSTEMI)
ACE inhibitor treatment at
discharge
zofenopril administered within
24h of symptoms and for 6 wk
12 mo
RCT
AMI (NR% NSTEMI)
captopril administered within 72h
placebo
3 mo
RCT
PS
14
Treatment
IIb/IIIa inhibitor type in pPCI
Statins (ACS)
Statins (NSTE-ACS)
Publication
information
1997, Am J
Cardiol29
Foy (PRACTICAL),
1994, Am J
Cardiol30
Akerblom, 2010,
JACC31
Zeymer (EVA-AMI),
2010, JACC32
Stenestrand, 2001,
JAMA33
Newby, 2002,
JAMA34
Smith, 2005, Am
Heat J35
Population
Intervention
Comparator
Outcome
(Mortality)
Design
of symptoms and for 4 wk
AMI (28% NSTEMI)
captopril or enalapril within 24h of
symptoms and for 12 mo
placebo
3 mo
RCT
STEMI treated with
primary PCI
STEMI, planned primary
PCI (95% received
primary PCI)
AMI (NR% NSTEMI)
eptifibatide
abciximab
12 mo
PS
eptifibatide
abciximab
6 mo
RCT
statin treatment at discharge
no statin treatment at discharge
12 mo
PS
ACS (NR% NSTE-ACS)
statin initiation within 7 d of ACS
no statin with 7 d of ACS
12 mo
PS
ACS (75% NSTE-ACS)
lipid-lowering therapy (94%
statin) started during index
hospitalization
statin within 96 h of symptom
onset
fluvastatin 80 mg within 1 h of
admission
fluvastatin 40 mg at least 1 d
prior to discharge and no later
than 14 d after AMI
pravastatin 10 mg in the week
after AMI onset
no lipid lowering therapy during
index hospitalization
10 mo
PS
no statin
24 mo
RCT
placebo
12 mo
RCT
placebo
12 mo
RCT
no pravastatin
9 mo
RCT
pravastatin 40 mg within 48 h of
admission
Combination treatment at
discharge consisting of aspirin,
clopidogrel and statin
lipid lowering agent treatment on
discharge (surrogate of statin
placebo
3 mo
RCT
Combination treatment at
discharge consisting of aspirin
and clopidogrel (no statin)
no lipid lowering agent on
discharge
6 mo
PS
6 mo
PS
Sakamoto, 2006,
Am J Cardiol9
Ostadal (FACS),
2010, Trials36
Liem (FLORIDA),
2002, Eur Heart J37
AMI (11% NSTEMI)
Sato (OACISLIPID), 2008, Circ
J38
Den Hartog, 2001,
Int J Clin Pract39
Lim, 2005, Eur
Heart J40
AMI (29% NSTEMI)
Aronow, 2001,
Lancet41
ACS (81% NSTE-ACS)
ACS (35% NSTE-ACS)
AMI (NR% NSTEMI)
ACS (NR% NSTE-ACS)
NSTE-ACS
15
Treatment
Publication
information
Population
Colivicchi, 2002,
Am J Cardiol42
NSTE-ACS
Schwartz
NSTE-ACS
(MIRACL), 2001,
JAMA43
Long-term mortality – non-pharmacological interventions
Invasive strategy (NSTE-ACS, Szummer
NSTEMI with CKD≥stage
CKD)
(SWEDEHEART),
3
2009, Circulation44
TIMI IIIB, 1994,
NSTE-ACS with
Circulation21
CKD≥stage 3
Intervention
treatment)
atorvastatin 80 mg on top of
conventional medical treatment
(including antilipidemic therapy
based on NCEP guidelines) at
discharge
atorvastatin 80 mg within 24-96 h
of admission
Comparator
Outcome
(Mortality)
Design
conventional medical treatment
(antilipidemic therapy based on
NCEP guidelines)
12 mo (stopped
early, all patients
followed up >=60
d postrandomization)
4 mo
RCT
placebo
RCT
revascularization within 14 d of
admission
no revascularization within 14 d
of admission
12 mo
PS
angiography within 48h of
randomization (followed by
revascularization, when
indicated) [89% received
revascularization during index
hospitalization]
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results) [65%
received revascularization
during index hospitalization]
12 mo
RCT
FRISC II, 1999,
Lancet22
NSTE-ACS with
CKD≥stage 3
angiography within 1 wk of
randomization (followed by
revascularization, when
indicated) [≈100% received
revascularization during index
hospitalization]
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results) [29%
received revascularization
during index hospitalization]
12 mo
RCT
Spacek (VINO),
2002, Eur Heart J23
NSTEMI with CKD≥stage
3
angiography within 24h of
symptom onset (followed by
revascularization, when
indicated) [85% received
revascularization during index
hospitalization]
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results) [71%
received revascularization
during index hospitalization]
12 mo
RCT
16
Treatment
Invasive strategy timing
(NSTE-ACS, elderly)
DES in pPCI
Publication
information
Cannon (TACTICSTIMI 18), 2001,
Circulation24
Population
Intervention
Comparator
Outcome
(Mortality)
12 mo
Design
NSTE-ACS with
CKD≥stage 3
angiography within 48h of
randomization (followed by
revascularization, when
indicated) [54% received
revascularization during index
hospitalization]
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results) [31%
received revascularization
during index hospitalization]
de Winter (ICTUS),
2005, NEJM45
NSTEMI with CKD≥stage
3
angiography within 48h of
randomization (followed by
revascularization, when
indicated) [79% received
revascularization during index
hospitalization]
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results) [41%
received revascularization
during index hospitalization]
12 mo
RCT
Bauer, 2007, Eur
Heart J46
NSTEMI, ≥75 years
angiography (followed by
revascularization, when
indicated) within index
hospitalization
angiography within 48h of
randomization (followed by
revascularization, when
indicated)
no angiography within index
hospitalization
12 mo
PS
Bach (TACTICSTIMI 18), 2004, Ann
Intern Med47
NSTE-ACS, >75 years
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results)
6 mo
RCT
Gurvitch, 2010, Int J
Cardiol48
Steg, 2009, Eur
Heart J49
Diaz de la Llera,
2007, Am Heart J50
Kelbaek
(DEDICATION),
2008, Circulation51
Stone (HORIZONSAMI), 2009, NEJM52
van der Hoeven
STEMI treated with
primary PCI
STEMI treated with
primary PCI
STEMI, candidates for
primary PCI
STEMI,candidates for
primary PCI
primary PCI with DES
primary PCI with BMS
12 mo
PS
primary PCI with DES
primary PCI with BMS
12 mo
PS
primary PCI with sirolimus-eluting
stents
primary PCI with DES
primary PCI with BMS
12 mo
RCT
primary PCI with BMS
8 mo
RCT
STEMI, candidates for
primary PCI
STEMI, candidates for
primary PCI with paclitaxeleluting stents
primary PCI with sirolimus-eluting
primary PCI with BMS
12 mo
RCT
primary PCI with BMS
12 mo
RCT
RCT
17
Treatment
Exercise rehabilitation (AMI)
Publication
information
(MISSION!), 2008,
JACC53
Valgimigli
(MULTISTRATEGY
), 2008, JAMA54
Laarman
(PASSION), 2006,
NEJM55
Chechi
(SELECTION),
2007, J Interv
Cardiol56
Meninchelli
(SESAMI), 2007,
JACC57
Spaulding
(TYPHOON), 2006,
NEJM58
Witt, 2004, JACC59
Population
Intervention
Comparator
Outcome
(Mortality)
Design
primary PCI
stents
STEMI, candidates for
primary PCI
primary PCI with sirolimus-eluting
stents
primary PCI with BMS
8 mo
RCT
STEMI, candidates for
primary PCI
primary PCI with paclitaxeleluting stents
primary PCI with BMS
12 mo
RCT
STEMI, candidates for
primary PCI
primary PCI with paclitaxeleluting stents
primary PCI with BMS
7 mo
RCT
STEMI, candidates for
primary PCI
primary PCI with sirolimus-eluting
stents
primary PCI with BMS
12 mo
RCT
STEMI, candidates for
primary PCI
primary PCI with sirolimus-eluting
stents
primary PCI with BMS
12 mo
RCT
AMI (NR% NSTEMI)
cardiac rehabilitation program
with exercise component
Cardiac rehabilitation invovling
group education or counseling
sessions about risk factor
management plus exercise
program
Cardiac rehabilitation involving
multidisciplinary team with
exercise rehabilitation and social
and psychological support
no cardiac rehabilitation
36 mo
PS
Sivarajan, 1982,
Circulation60
AMI (NR% NSTEMI)
control group
6 mo
RCT
Vermeulen, 1983,
Am Heart J61
AMI (NR% NSTEMI)
control group
12 mo
RCT
WHO trial, 1983,
WHO62
AMI (NR% NSTEMI)
Cardiac rehabilitation involving
multidisciplinary team for patient
health
education and supervised
exercise program
control group
36 mo
RCT
18
Treatment
Complete PCI
revascularization (STEMI)
Publication
information
Fridlund, 1991,
Scan J Caring Sci63
Population
Intervention
Comparator
Outcome
(Mortality)
12 mo
Design
AMI (NR% NSTEMI)
control group (routine cardiac
followups)
Oldridge, 1991, Am
J Cardiol64
AMI patients (NR%
NSTEMI)
Nurse-led cardiac rehabilitation
program addressing lifestyle,
stress, and social support plus
exercise component
cardiac rehabilitation involving
behavioral counseling and
supervised exercise training
control group (usual care)
12 mo
RCT
PRECOR, 1991,
Eur Heart J65
AMI patients (NR%
NSTEMI)
cardiac rehabilitation involving
supervised exercise program,
relaxation
training, risk factor management
and education
cardiac rehabilitation involving
nurse-managed patient education
and
counseling, exercise program,
frequent telephone contact, and
algorithm-based
lipid therapy
Cardiac rehabilitation involving
supervised exercise program,
group
education sessions on risk factor
management
Cardiac rehabilitation involving
supervised exercise training and
education or
counseling about risk factor
management, with optional
monthly support groups
control group (usual care)
24 mo
RCT
deBusk, 1994, Ann
Intern Med66
AMI patients (NR%
NSTEMI)
control group (usual care)
12 mo
RCT
Bell, 1998,
unpublished
AMI patients (NR%
NSTEMI)
control group (usual care)
12 mo
RCT
Marchionni, 2003,
Circulation67
AMI patients (NR%
NSTEMI)
no cardiac rehabilitation
12 mo
RCT
Kalarus, 2007, Am
Heart J68
STEMI patients with
multivessel CAD
complete PCI revascularization
incomplete PCI
revascularization
29 mo
PS
RCT
19
Treatment
Invasive strategy (NSTE-ACS)
Publication
information
Di Mario, 2004, Int J
Cardiovasc
Intervent69
Politi, 2009, Heart70
Ottervanger, 2004,
Eur Heart J71
TIMI IIIB, 1994,
Circulation21
Population
Intervention
Comparator
STEMI patients with
multivessel CAD
complete PCI revascularization
culprit only PCI
revascularization
STEMI patients with
multivessel CAD
NSTE-ACS patients (30 d
survivors)
NSTE-ACS patients
complete PCI revascularization
culprit only PCI
revascularization
no revascularization within 30d
of presentation
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results) [40%
received revascularization
during index hospitalization]
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results) [9%
received revascularization
during index hospitalization]
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results) [39%
received revascularization
during index hospitalization]
early conservative strategy
(angiography performed when
indicated by symptoms or
functional test results) [36%
received revascularization
during index hospitalization]
early conservative strategy
(angiography performed when
indicated by symptoms or
FRISC II, 1999,
Lancet22
NSTE-ACS patients
Spacek (VINO),
2002, Eur Heart J23
NSTEMI patients
Cannon (TACTICSTIMI 18), 2001,
Circulation24
NSTE-ACS patients
Fox (RITA 3), 2002,
Lancet25
NSTE-ACS patients
revascularization within 30d of
presentation
angiography within 48h of
randomization (followed by
revascularization, when
indicated) [60% received
revascularization during index
hospitalization]
angiography within 1 wk of
randomization (followed by
revascularization, when
indicated) [71% received
revascularization during index
hospitalization]
angiography within 24h of
symptom onset (followed by
revascularization, when
indicated) [78% received
revascularization during index
hospitalization]
angiography within 48h of
randomization (followed by
revascularization, when
indicated) [60% received
revascularization during index
hospitalization]
angiography within 3 d of
randomization (followed by
revascularization, when
Outcome
(Mortality)
12 mo
Design
12 mo
RCT
12 mo
PS
12 mo
RCT
12 mo
RCT
6 mo
RCT
6 mo
RCT
24 mo
RCT
RCT
20
Treatment
Publication
information
Population
Intervention
Comparator
Outcome
(Mortality)
Design
indicated) [44% received
functional test results) [10%
revascularization during index
received revascularization
hospitalization]
during index hospitalization]
Boden
NSTEMI patients
angiography within 3 d of
early conservative strategy
23 mo
RCT
(VANQWISH),
symptom onset (followed by
(angiography performed when
1998, NEJM26
revascularization, when
indicated by symptoms or
indicated) [44% received
functional test results) [33%
revascularization during index
received revascularization
hospitalization]
during index hospitalization]
ACS = acute coronary syndrome; CAD = coronary artery disease; d = days; mo = months, NR = not reported; NSTE = non-ST-elevation; NSTEMI,
non-ST-elevation myocardial infarction; PCI = percutaneous coronary intervention; RCT = randomized controlled trial; STEMI = ST-elevation
myocardial infarction.
21
Appendix Table 2: Study design and statistical methods reporting characteristics of the
21 observational studies that used propensity-score methods.
Characteristics
Study design
Prospective
Patient sampling from RCT population
Administrative dataset
Statistical analyses unrelated to PS
Reporting of analyses based on multivariate regression methods
without PS
Statistical analyses related to developing the PS
PS estimation method
Reporting of variables used for PS estimation
Reporting of variable selection method
Reporting of AUC for the PS model
Median AUC (25th-75th percentile)
Statistical analyses related to developing the PS
Matching on PS (5 studies, all used 1:1 matching)
Process of matching reported
Assessment of covariate balance between matched pair groups
N of matched pairs (median)
N of treated patients left unmatched (median)
N of treated patients left unmatched (median)
Analysis method accounting for matching
N (%)
Yes
No
Yes
No
Yes
No
19 (90%)
2 (10%)
4 (19%)
17 (81%)
1 (5%)
20 (95%)
Yes
No
11 (55%)
10 (45%)
Logistic
regression
Other model
Yes
No
Yes (stepwise
selection in all
cases)
No
Yes
No
20 (95%)
No
Yes
No
Yes
Yes
No
1 (5%)
18 (95%)
3 (5%)
10 (48%)
11 (52%)
11 (52%)
10 (48%)
0.78 (0.69-0.81)
2 (40%)
3 (60%)
2 (40%)
3 (60%)
9819
1113
23785
2 (40%)
3 (60%)
Stratification based on PS (4 studies, all using 5 strata)
Assessment of covariate balance following stratification
Yes
2 (50%)
No
2 (50%)
Method for estimating treatment effect across strata
IV
2 (50%)
Other/NR
2 (50%)
Regression analysis with PS included as a covariate in the model (18 studies)
Specification of the functional form for the PS variable in the model
No
14 (78%)
Yes
4 (22%)
No study used the propensity score to derive inverse probability of treatment weights. For studies that used
the PS in multiple analytic approaches (for example, regression and stratification) we extracted information
for all performed analyses, even if treatment effect estimates were not reported from some. Of the studies
using both regression- and non-regression-based analyses utilizing the PS, only 3 reported treatment effect
estimates from both approaches.
IV = inverse variance; NR = not reported; PS = propensity score
22
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27