DOI: 10.1161/CIRCULATIONAHA.114.013451
Doing the Right Things and Doing Them the Right Way:
The Association Between Hospital Guideline Adherence, Dosing Safety, and
Outcomes Among Patients with Acute Coronary Syndrome
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
Running title: Mehta et al.; Quality, Safety and Outcomes
Alexander
err, MD;
MD;
Rajendra H. Mehta, MD, MS; Anita Y. Chen, MS; Karen P. Alexander,
E. Magnus Ohman, MD; Matthew T. Roe, MD, MHS; Eric D. Peterson, MD, MPH
liinic
nicall Rese
R
ese
sear
arch
ar
ch IInstitute
nsstiitu
tute
t aand
te
nd
dD
ukee U
uk
niv
verrsi
sity
ty M
e ical
ed
ical C
enteer,
r, D
urha
ur
ham
ha
m, N
m,
C
Duke C
Clinical
Research
Duke
University
Medical
Center,
Durham,
NC
Address for Correspondence:
Rajendra H. Mehta, MD, MS
Duke Clinical Research Institute and Duke University Medical Center
2400 Pratt Street
Durham, NC 27705
Tel: 919-668-8971
Fax: 919-668-7056
E-mail: raj.mehta@dm.duke.edu
Journal Subject Code: Ethics and policy:[100] Health policy and outcome research
1
DOI: 10.1161/CIRCULATIONAHA.114.013451
Abstract
Background—Performance metrics currently focus on measurement of application of
guidelines-indicated medications without considering appropriate dosing of these drugs.
Methods and Results—We studied 39,291 patients from CRUSADE with non-ST-segment
elevation acute coronary syndromes. We evaluated hospital variability in composite use of
ACC/AHA guidelines-recommended therapies (adherence) and the proportion of treated patients
with recommended dose of heparins or a Gp IIb/IIIa antagonists (safety), and its association with
risk adjusted in-hospital mortality and bleeding. Rates of composite guideline adherence (median
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
85% [25th, 75th percentile 82, 88]) and antithrombotic dosing safety (53% [45%, 60%]) varied
among hospitals. Correlation between hospital composite adherence and safety metrics was
significant
g
but low (r=0.16,
(
, p=0.008).
p
) Risk adjusted
j
in-hospitals
p
mortalityy was inverselyy related
o both guidelines adherence (OR-10% increment 0.80, 95% CI 0.67-0.94) and sa
afeety m
etri
et
rics
ri
c
cs
to
safety
metrics
OR-10% increment 0.90, 95% CI 0.83-0.98). Safety was inversely related to major bleeding
(OR-10%
adjusted OR-10%
0% increment 0.93, 95% CI 0.87-0.98).
0.87
7-0.98). Compared with hospitals with low
(adjusted
adherence
ad
dhe
herrenc
ren e an
andd sa
safe
safety
fety
ty (
(median
me
medi
d an
n performance)
perfo
f rm
rman
ance)) metrics,
mettriics, those
me
tho
hosse withh mixed
mix
xed pperformance
erfoorm
mancee m
metrics
ettrics
(high
hig
gh adherenc
adherence
ncee an
and
nd lo
low
w sa
safe
safety,
fety
fe
ty,, lo
ty
low
ow aadherence-high
dherennce-hi
nc igh saf
safety)
afet
af
etyy)
y) hhad
ad in
intermediate
nte medi
nter
mediat
atte ri
risk
skk aadjusted
djus
dj
usteed
mo
orttal
a it
ity ra
rate
tess whil
te
w
hilee hhospitals
osp
spittals
al wi
with
th
h aabove
bove
ve av
verag
eragee perf
pperformance
erf
rfoorm
ormance
nce onn bot
othh me
etr
tric
i s (>
ic
>meddiaan
an
mortality
rates
while
average
both
metrics
(>median
performance)
perf
rfor
orma
m nc
nce) had
had
a a trend
tre
rendd for
forr lowest
low
owes
e t riskk adjusted
adju
just
sted
ed mortality
mor
orta
tali
lity
ty rrates
ates (O
at
(OR
R 0.
00.83,
83
3, 95
95%
% CI
C 00.68-1.01).
. 8.6
8-1.
1 01
0 ).
)
Hospitals
Hosp
pitals with
wiith high
hig
ighh safety
safe
sa
feety had
had lower
low
wer
e bleeding
ble
leed
ed
dingg compared
com
ompa
pare
pa
redd to tthose
hose
ho
se w
with
ithh lo
it
low
w sa
safe
safety.
fety
fe
ty.
Conclusions—Guideline adherence and dosing safety appeared to provide independent and
complementary information on hospital bleeding and mortality supporting the need for broader
metrics of quality that should include measures of both guideline-based care and safety.
Key words: quality, safety, acute coronary syndrome, outcome
2
DOI: 10.1161/CIRCULATIONAHA.114.013451
Introduction
There is interest and initiatives to measure, monitor and improve hospital quality of care from
such organizations as the Center for Medicare and Medicaid Services, the Veterans Healthcare
Affairs Administration, major insurers, Joint Commission for Accreditation of Healthcare
Organization (JCAHO) as well as from professional societies such as the American College of
Cardiology (ACC), the American Heart Association (AHA).1-8 Such performance measurement
systems have traditionally centered on assessing hospitals’ use of evidence-based care processes,
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
equating this in most cases to ‘quality’.1-8 Reducing such ‘errors of omission’ (i.e. failure to
provide evidence-based therapies) is clearly important and has been shown to be associated with
better patient outcomes.9 However, based on ample evidence, the Institute of Medicine
Med
ed
diccin
inee ((IOM)
IOM)
IO
M)
also specifically points out that ‘errors of commission’, such as incorrect dosing of therapies or
their
heiir inappropriate
inap
in
appr
prop
pr
op
priat
atee use
at
use in patients in whom theyy are
aree contraindicated,
contraindicatted
e , are
arre equally
equally common and
10-12
0-12
12
2
costly
co
osttly
l and com
compromise
mpromis
isee patients’
pati
pa
tien
ti
entts’
en
ts safety
safe
sa
f ty
fe
y i.e.
i.e. causing
causin
cau
ng harm
rm to
to them.
th
hem
m.10D
Despite
espi
espi
pite
tee this,
thiis, to
to date,
d te
da
te, no
study
tud
udyy has
h s examined
ha
exaamin
ex
amin
ned the
the correlation
cor
orreela
lati
tion
ti
on between
bettwe
ween
en hospital
hos
ospi
pitaal adherence
pi
adhe
adhe
herrenc
rencce with
with gguidelines-recommended
uiddeli
deliine
ness reeco
scomm
mm
men
e ded
therapies
herapies andd appropriate
appr
ap
prop
pr
opri
op
riiatte dosing
dosi
do
s ng
si
g of
of these
t es
th
esee medications
medi
me
d ca
di
cati
tion
ti
onss tthat
on
hatt af
ha
affe
affect
fect
fe
ct pat
patients
atie
at
ieent
ntss sa
safe
safety.
fety
ty.. Fu
ty
Furt
Furthermore,
rthe
rt
h rmore, th
the
he
relationship of hospital compliance with these matrices of quality and safety with outcomes of
patients at these institutions remains unknown.
Using data from the large national quality improvement initiative, CRUSADE (Can
Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early
Implementation of the ACC/AHA Guidelines), the purpose of current study was to evaluate
whether quality and safety process performance metrics, individually and in combination, are
associated with in-hospital patient outcomes among non-ST-elevation acute coronary syndromes
(NSTE ACS) patients.12-16 We hypothesized that while both adherence to guideline-based
3
DOI: 10.1161/CIRCULATIONAHA.114.013451
therapies and their safe use in appropriate doses would be significantly associated with patient
in-hospital outcomes, hospitals that performed better on the two together (i.e. adherence to
guideline-based therapies and safety metrics) would have best patient outcomes.
Methods
CRUSADE Registry and Patient Population
The details of the CRUSADE initiative have been previously published.12-16 In brief, patients
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
admitted to 501 participating hospitals in U.S., who were included in the ongoing CRUSADE
Quality Improvement Initiative, had ischemic symptoms at rest within 24 hours prior to
presentation and high-risk ffeatures including ST-segment de
pression, transient ST
T-sseg
gme
ment
nt
depression,
ST-segment
elevation, and/or positive cardiac markers (elevated troponin I or T and/or creatine kinase (CK)MB
B >upper
>uppe
uppeer limit
limiit of
li
of normal for participating institutions).
insttitu
itutions).
Data we
wer
re ccollected
ollle
l ct
cted
ed oonly
nlyy du
nl
duri
r ng tthe
ri
he hhospitalization
ospiita
tallizaatiion inn an aanonymous
nony
no
nyymous
mous ffashion
ashi
as
hionn w
hi
ittho
houut
ut
were
during
without
nfo
form
rm
med cconsent
onse
on
sennt
nt after
aft
fter
er tthe
h individual
he
ind
ndiv
nd
iv
vid
idua
uall institutional
ua
inst
stit
ituutio
it
ona
n l review
reviiew
w board
boaard approved
app
ppro
r vedd pa
ro
arttic
i ip
ipat
attionn in
n tthis
his
informed
participation
quality improvement
imprrovvem
emen
entt initiative.
en
i it
in
i iaati
tive
v . Data
ve
Dataa collected
col
olle
ol
leect
cted
ed included
incclud
uded
ed baseline
bas
asel
elin
el
in
ne clinical
c in
cl
inic
ical
ic
al characteristics,
char
a ac
acte
teri
te
rist
ri
stic
st
i s, use of
ic
acute medications, use and timing of invasive cardiac procedures, laboratory results, in-hospital
clinical outcomes, and discharge therapies and interventions. Decisions regarding the use of
invasive procedures were made by the treating physicians. Contraindications to specific therapies
given Class IA or IB recommendations by the existing ACC/AHA Guidelines at the time of
study period were recorded.17
We analyzed treatment and appropriate dosing patterns among patients with high-risk
NSTE ACS included in the CRUSADE at hospitals in the United States from January 2004
through June 2005 (n=59,023, 425 sites).12-16 From this sample, we successively excluded
4
DOI: 10.1161/CIRCULATIONAHA.114.013451
patients with missing weight and creatinine clearance information (n=3,659), those not receiving
any heparin or glycoprotein IIbIIIa anatagonists (n=8,726), and those with missing dose
information of these agents (n=5,124). Finally, patients at sites that enrolled less than 40 patients
were also excluded from this analysis (n = 2,223 patients, 124 sites). Our final analysis
population contained 39,291 patients treated at 283 hospitals.
We evaluated the use of the then existing American College of Cardiology
(ACC)/American Heart Association (AHA) 2002 Class I guideline-recommended therapies.
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
During the study period.17 The therapies included: aspirin and/or clopidogrel, glycoprotein
IIb/IIIa inhibitor, any heparin (unfractionated or low molecular heparin), and ȕ-blocker used
within the first 24 hours of hospital arrival and aspirin and/or clopidogrel, ȕ-blocker,
ȕ-block
ck
kerr,
angiotensin-converting enzyme inhibitor or angiotensin receptor blocker among ideal patients
defined
de
efi
fine
nedd ass ppatients
ne
a ient
at
ntss with
nt
w th left ventricular dysfunction
wi
dysfuncttion
ion (ejection frac
fraction
cti
t on
n<
<40%),
40
40%),
heart failure,
ddiabetes
diab
i bet
e es mellitus
melliitu
tuss or
or hypertension;
hyper
yper
erte
tens
te
nsiion;
ns
ion;; and
and
n any
any lipid-lowering
lip
i id-low
owerin
ow
ingg agents
in
agents
age
ents aamong
monng iideal
mo
deal
de
al ppatients
atie
at
iennts
ie
nts de
defi
defined
fine
fi
need as
patients
pati
pa
tien
ti
en
nts
t with
wit
ithh documented
docu
do
cume
cu
m nteed
me
ed hyperlipidemia
hyp
yper
errli
lipi
piddemi
pi
demi
miaa and/or
and/
an
d//or
o measured
meassurred low-density
me
low
ow-d
-d
den
nsi
s ty
y llipoprotein
i oppro
ip
ote
tein
in ccholesterol
hooleest
ster
erroll
(>100
>100 mg/dL).
mg/dL)
L)..
L)
For assessing hospital safety performance, we focused on their appropriate dosing of
intravenous heparin or low molecular weight heparin or glycoprotein IIbIIIa inhibitors using
previously described methodology.12 Excess dosing of these agents were considered as any bolus
dose >70 units/kg and/or any maintenance dose >15 Units/Kg/hour for unfractionated heparin, or
>1.05 mg/kg twice daily for low molecular weight heparin, or full dose of tirofiban for creatinine
clearance <30 ml/min or full dose of eptifibatide for creatinine clearance <50 ml/min. Composite
hospital adherence rates were determined using previously described method and consistent with
that used by Center for Medicare and Medicaid Services.18 Hospital composite adherence scores
5
DOI: 10.1161/CIRCULATIONAHA.114.013451
and hospital composite safety metric were defined as the ratio of total received therapies (or total
received appropriate dose) for all patients at a single hospital out of the total number of
opportunities for all patients at that hospital. The hospital composite adherence scores and safety
metrics were analyzed as continuous variables and quartiles of hospital composite adherence
scores, where the 1st quartile (Quartile 1) consisted of hospitals with the lowest composite
adherence scores and the 4th quartile (Quartile 4) consisted of hospitals with the highest
composite adherence scores.18 Furthermore, hospitals were grouped into 4 performance
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
quadrants based on their guidelines adherence rates (superior or inferior to median performance)
and antithrombotic dosing safety profile (superior or inferior relative to median performance):
Low Adherence and Safety, Low Adherence and High Safety, High Adherence an
nd Lo
ow Sa
Saf
fety,,
fety
and
Low
Safety,
and High Adherence and Safety.
Outc
Ou
tcoomes
tc
ess ooff interest included all cause in
in-h
-h
hospital mortal
lit
i y an
nd ma
m
jor bleeding. Major
Outcomes
in-hospital
mortality
and
major
bbleeding
leeedi
d ng was ddefined
efin
ef
ned
d aass an
ny on
onee of
o tthe
hee ffollowing:
ollow
owing:: A
ow
bssollut
utee hem
hhematocrit
emattocr
crit
it ddrop
ro
op of
of >
12%,
12
%,
any
Absolute
>12%,
intracranial
ntr
trac
acra
ac
rani
ra
nial
all hhemorrhage,
emor
em
orrh
or
r ag
rh
age,
e,, documented
doccum
umen
ente
en
tedd retroperitoneal
te
retr
retr
trop
operrit
op
iton
onneaal blee
bbleeding,
lee
eedi
ding
di
ng
g, bbaseline
ase
seli
se
l ne
li
ne hhematocrit
em
mattoc
o ri
ritt <2
<28%
8% w
with
ithh
blood transfus
transfusion,
ussio
ion,
n, aand
nd bbaseline
assel
elin
ine he
in
hema
hematocrit
mato
ma
ocr
crit
it >
>28%
2 % with
28
with
t blood
blo
lood
od transfusion
tra
rans
n fu
fusi
siion and
and witnessed
witn
wi
tnes
tn
esse
es
s d bleeding
se
g
event.19
Statistical Analysis
For descriptive purposes, hospitals were grouped into 4 performance quadrants based on their
guidelines adherence rates (superior or inferior to median performance) and antithrombotic
dosing safety profile (superior or inferior relative to median performance). Patient baseline
demographics, clinical and hospital characteristics, care patterns, and in-hospital outcomes were
presented according to the combined safety-adherence profiles. Continuous variables were
described using median (25th and 75th percentile) values and categorical variables were described
6
DOI: 10.1161/CIRCULATIONAHA.114.013451
as percentages. In addition, the association between hospital adherence and safety performance
rates was summarized based on a weighted Pearson correlation using inverse variances of safety
performance as the weights.
In examining the association between guidelines-based treatments and in-hospital clinical
outcomes, we further excluded patients transferred out (n=4,687). Also, and particularly for the
end-point of major bleeding, we excluded those that underwent coronary artery bypass surgery
(CABG) (n=4,361) given that loss of blood in patients undergoing CABG is common and
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
expected. Failure to exclude these patients is likely to bias CABG hospitals as having higher
major bleeding. Logistic generalized estimating equations (GEE) method with an exchangeable
working correlation matrix was used to account for within-hospital clustering, wh
herre pa
pati
tien
ti
ents
en
t aatt
ts
where
patients
he same hospital were more likely to have similar outcomes relative to patients in other
the
ho
osp
spit
ital
it
alss (e
al
(e.g
.g. wi
ith
thin
in-center correlation for outc
com
o es).20 Previousl
Previously
sly pu
sl
published
ubl
blis
i hed bleeding model
hospitals
(e.g.
within-center
outcomes).
w
was
ass used
u ed to risk
us
riiskk adjust
addjus
ustt for
for he outcome
out
utccom
come
me of
of bleeding.
bllee
eedingg.1199 V
Variables
ariabl
aria
b es entered
bl
enterred into
int
ntoo the
the in-hospital
in
n-h
hos
o pi
p ta
tall
mo
mortality
ort
r al
alit
i y mo
it
mod
model
del were
del
were the
the
he common
com
mmo
monn predictors
predic
pre
icto
torrs of
to
of in
in-hospital
n-hospi
pita
tall mortality
ta
mort
mo
rttallit
ityy risk
riskk among
amo
mong
ng patients
patieent
ntss with
wiith
h
21-23
23
acute coronary
coronaary
y syndromes
syn
yndr
d om
dr
omess reported
repo
p rt
rted
e in
ed
in prior
prio
pr
iorr li
io
literature.
ite
tera
ratu
ra
ture
tu
ree.21
From
Fr
om the
thee full
ful
ulll li
list
st of
of th
thes
these
esee predictors
es
p edictors of
pr
o
mortality, investigators carefully determined the clinically relevant covariates available in the
CRUSADE Registry that were then included in the model as described in previous publications
from this registry.14,24 Patient baseline characteristics in the in-hospital mortality model included
age, male sex, body mass index, white race, insurance status, hypertension, diabetes,
current/recent smoking, prior myocardial infarction, renal insufficiency, positive cardiac
markers, clinical signs of heart failure on presentation, presenting heart rate and systolic blood
pressure. Hospital characteristics in the model included total number of hospital beds,
geographic region (West, Northeast, Midwest, or South), revascularization capabilities (no
7
DOI: 10.1161/CIRCULATIONAHA.114.013451
services, diagnostic catheterization only, percutaneous coronary intervention without on-site
cardiac surgery, percutaneous coronary intervention with on-site cardiac surgery), and hospital
affiliation (academic versus non-academic). In the model, adherence to guideline-based
treatments was modeled as highest quartile vs. 3rd quartile, highest quartile vs. 2nd quartile and
highest quartile vs. lowest quartile and furthermore as a continuous metric. In exploring the
relationship between safety and outcomes, similar approach was used. Furthermore, the
association between both adherence to recommended treatments and safety performance and
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
outcomes were also explored. Using logistic GEE method and the same list of covariates, we
compared both high adherence and safety, low adherence-high safety, and high adherence-low
afety, with both low adherence and safety as referent group. Moreover, we perf
forme
m da
safety,
performed
ensitivity analysis by excluding hospitals without CABG capabilities (n=7,162) and repeating
sensitivity
he main
main analysis.
ana
n lysiis.
s. For
F r all of the models, the same
Fo
sam
me set
set of covariates
covariattes
e was
was included
included even if some of
the
he covariates
c variatess were
co
wer
e e not
noot statistically
stat
st
atis
at
isti
is
tica
ti
call
llly significant.
s gni
si
gnificaant
ant. A pp-value
-vaalu
alue
ue ooff <
0.05
0.
05
5w
ass cconsidered
on
nsid
sidere
dereed statistically
s attissti
st
tica
caall
ly
the
<0.05
was
ign
gnif
iffic
ican
antt for
for all
all tests.
testss. All
test
All analyses
ana
n ly
lyse
sess were
se
weeree performed
perffor
pe
o med
med using
usin
in
ng SAS
SA
AS software
sooft
ftwa
waree (version
wa
(veerssio
ionn 9.3,
9.3, SA
AS
AS
significant
SAS
nstitute, Cary,
Carry, N
C)..
C)
Institute,
NC).
Results
Among CRUSADE NSTE ACS patients, the overall composite median adherence rate for the
ACC/AHA guidelines recommended therapies was 85% (25th, 75th percentile 82% and 88%).
The median hospital safe drug-dosing rate was 53% (45%, 60%). There was a significant but
low correlation between composite guideline medications use and the dosing appropriateness
metrics (r = 0.16, p =0.008) (Figure 1).
Table 1 provides baseline demographics, clinical and hospital characteristics of patients
8
DOI: 10.1161/CIRCULATIONAHA.114.013451
treated at centers within each of the four performance-based categories. In general, patients in
the hospitals that had low composite adherence to guideline-based therapies and medication
dosing safety profiles were more likely to be older, female, and had more comorbid conditions
including diabetes mellitus and prior congestive heart failure. Similarly, this cohort was more
likely to have higher heart rate and lower systolic blood pressure and creatinine clearance on
admission. Additionally, the institutions with both low adherence and low safety were more
likely to be smaller hospitals that were less likely to have capabilities for percutaneous or
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surgical coronary revascularization, and with patients less likely to be treated by a cardiologist.
Table 2 displays actual treatment and dosing patterns among the various hospital quartile
were
groupings. In general, patients in hospitals that had low adherence and safety w
eree le
less
ss llikely
ikel
ik
elyy to
el
receive
eceive guideline-based therapies (Table 2). Particularly, the use off aspirin and beta-blockers
within
with
wi
th
hin 24
24 hours
houurs of admission
ho
admission and at discharge, glycoprotein
glyc
gl
yccoprotein IIbIIIa
IIbIIIIa
I inhibitor
inh
nhhib
ibit
i or within 24 hours and
angiotensin
an
ngiot
o ensin converting
co
onv
verrtiing enzyme
enz
nzym
ymee inhibitors
ym
in
nhi
hibbittorrs orr angiotensin
angioote
otenssin receptor
rece
re
ceept
ptoor blockers,
bloc
ocke
k rs
ke
rs,, clopidogrel
clop
cl
opid
id
doggre
rell an
andd
statins
group
compared
with
tat
atin
inss at discharge
in
dis
isch
char
arrgee were
weree all
al lower
lowe
lo
werr in this
we
thiss gr
grou
oupp co
ou
ompa
mpared
ed w
itth pati
ppatients
ati
tien
e ts in
en
in hospital
hosp
ho
sppit
ital
al that
tha
hatt had
had high
higgh
gh
adherence an
and
Similarly,
nd sa
ssafety.
fety
fe
ty. Si
ty
imiila
larl
r y, eexcessive
rl
xcces
e si
sive
ve ddosing
osin
os
i g of aany
in
ny
y hheparins
epar
ep
arin
ar
inss or gglycoprotein
in
lyco
ly
copr
co
p ot
pr
otei
einn II
ei
IIIbIIIa
b IIa
bI
inhibitors was highest among patients in hospital that had both low adherence and safety.
There was a significant association between hospital’s composite guidelines adherence
rates and unadjusted in-hospital mortality. For every 10% increase in composite adherence at a
center, the patient’s in-hospital mortality odds ratio fell by a corresponding 39% (OR 0.61, 95%
CI 0.50-0.75). Similarly, for every 10% increase in appropriate dosing at a center, the patient’s
in-hospital mortality odds ratio fell by a corresponding 18% (OR 0.82, 95% CI 0.73-0.93). These
relationships of care and in-hospital mortality (adjusted OR for 10% increment 0.80, 95% CI
0.67-0.94) and safety and in-hospital mortality (adjusted OR for 10% increment 0.90, 95% CI
9
DOI: 10.1161/CIRCULATIONAHA.114.013451
0.83-0.98) persisted even after adjustments for various confounders.
Non-CABG in-hospital major bleeding was directly related to guideline-based adherence.
Improved adherence to guideline-based treatments increased the risk of bleeding (adjusted OR
for 10% increment 1.25, 95% CI 1.08-1.44). In contrast, appropriate dosing (safety) was
inversely related to major bleeding (adjusted OR for 10% increment 0.93, 95% CI 0.87-0.98).
When we looked at hospital categories based on combination of both adherence with
guideline-based treatment and appropriate dosing, the lowest unadjusted in-hospital mortality
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was observed in the high adherence and high safety group, highest in the low adherence and low
safety group, and intermediate in the high adherence low safety and low adherence and high
safety
afety groups (Figure 2A). Similar findings were noted after
f adjustments for patients’
pati
tiien
nts’’ an
andd
hospital characteristics, although the relationship was significantly attenuated (Table 3).
Non-CABG
adherence-safety
NonNo
n CABG
nCABG in-hospital major bleeding rrates
ates in the four ad
ate
dhe
h reenc
ncee safety category
hospitals
are sh
shown
Figure
4),
with
lower
unadjusted
bleeding
hospitals
hosp
p
how
wn in Fi
Figu
gure
gu
re 22B
B ((Table
Tablee 4)
Tabl
), w
ithh lo
oweer un
unad
ad
dju
jussteed aand
n adjusted
nd
adj
djus
uste
us
tedd bl
blee
e di
ee
d ng rrates
ates
inn tthe
groups
he ttwo
wo hhigh
ighh ssafety
ig
affety
fety
y ddosing
osi g gr
osin
grou
oups
ou
p ccompared
ps
ompa
om
pare
pa
r d with
re
wi h their
thheir
heir counterparts
cou
unt
n erpa
erpa
part
r s with
rt
with low
low
w or
or high
high
gh
adherence too guideline-based
safety.
gui
u de
deli
line
li
nee-b
bassed care
caare tthat
h t ha
ha
hadd lo
low
w sa
afe
fety
ty.
ty
Finally, sensitivity analysis performed excluding patients from hospitals with CABG
capabilities, continued to show similar relationship in the four adherence-safety categories with
the lowest in-hospital mortality in the high adherence and high safety group (data not shown).
Discussion
Institute of Medicine defines ‘quality health care’ as not only the use of effective evidence-based
medicine, but also as that which is safe, patient-centered, timely, efficient and equitable. Thus
safety has been regarded as the foundation upon which all other aspects of quality care are built.
10
DOI: 10.1161/CIRCULATIONAHA.114.013451
However, commonly quality in health care is often talked about in terms of achievement of one
or other goals (rather than more than one simultaneously) and in most cases is considered to be
synonymous with the use of evidence-based medicines.1-7,25 Thus, the Center for Medicare and
Medicaid Services and many payers have focused on monitoring adherence to guideline-based
treatment as being the evidence of better ‘quality of care’.8 The awareness of the importance of
patient safety is further highlighted by the Institute of Medicine report ‘To Err is Human:
Building a Safer Health System’ that suggest that many lives can be saved each year in United
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States by focusing on preventing ‘harm’ caused by medication errors.26 Recognizing the
importance of patient safety, many accreditation agencies such as the Joint Commission on
Accreditation of Healthcare Organization have directed their efforts towards imp
improving
provi
v ng ssafety
vi
afet
af
etyy
et
for patients and residents in health care organizations.27 This commitment is inherent in its
mi
miss
ssio
ss
ionn to ccontinuously
io
ontiinu
nuou
ously improve the safety and quality
quality of care pr
rov
o id
ded tto
o the public through the
mission
provided
prov
provision
vision of hhealth
ealt
ea
l h ca
car
care
re aaccreditation
ccre
cc
redi
re
dita
tati
tioon
ti
on aand
nd re
related
elaated se
services
erviicees tha
tthat
hat
at su
support
uppor
ortt pe
performance
erf
rfoorm
ormanc
mancce im
improvement
mprrovem
ovem
emen
in
n hhealth
eaalt
lthh ca
care
are oorganizations.
rgaaniz
rg
anizaatiions
n . De
Desp
Despite
spit
sp
itee th
it
this
hiss ggrowing
row
ro
win
i g aawareness,
waren
aren
eneess,
es , tthe
hee aassociation
ssoociaatio
ss
ationn betw
bbetween
etw
wee
een ho
hosp
hospital
spit
ittall
use of guideli
guideline-based
line
ne-b
ne
-b
bas
ased
ed
d ttherapy
hera
he
rapy
ra
p aand
py
n pa
nd
ppatient
tiien
entt sa
safe
safety
f ty aass well
fe
w ll as
we
as their
thei
th
eirr association
ei
assso
soci
ciat
ci
atio
at
ionn wi
io
with
th in-hospital
inn ho
h spital
outcomes remain less known.
Our study is the first in the field to provide an important insight into this association.
Contrary to our hypothesis, we found that there was limited association between prescription of
appropriate guideline-based treatments and patient safety record of an institution such that
institutions that had better adherence to evidence-based therapies did not necessarily have good
safety record and vice versa. Importantly, our data found that the overall better guideline
adherence and safety profiles were independently and incrementally associated with lower rates
of in-hospital death. In fact, the best in-hospital outcomes were seen in institutions that excelled
11
DOI: 10.1161/CIRCULATIONAHA.114.013451
at both safety and guideline-based therapies, whereas the worst outcomes occurred at institutions
with poor record of both these measures. Thus, there was a 42% decrease odds of unadjusted
overall in-hospital mortality in institutions that performed well on adherence to guidelinerecommendation and had better patient safety compared to those that did poorly on both these
measures. This reduction in death was much greater than the approximate 19%-31% reduction in
unadjusted odds of mortality observed at institutions that either excelled in evidence-based
treatments or patients safety, but not both. Additionally, our data indicates that focusing only on
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
guideline-based therapies (to improve ‘report-card’) without paying attention to safety could be
potentially dangerous as this often leads to increased risk of non-CABG major bleeding. This
guideline-based
was supported by the fact that among patients with low or high adherence to guid
id
dellin
i e--ba
base
sedd
se
care, the risk of non-CABG major bleeding was lower in those with higher safety compared with
those
hosse with
with lower
low
werr safety.
saf
a ety.
categories
our
was
While aamong
mong
mo
ng tthe
hee hhospital
ospi
os
pita
pi
tall ca
cate
tego
go
oriess inn ou
ur sstudy
tu
udy tthere
herre
re w
as a ssignificant
i nifi
ig
nifiica
cant
nt ttrend
rend
nd ffor
orr
decreasing
in-hospital
with
mortality
high
decr
de
crea
cr
easi
ea
s ng uunadjusted
si
nadj
nadj
djusste
tedd in
n-h
-hosspi
pita
tall mortality
ta
m rttallit
mo
ityy wi
ith llowest
ow
west mo
mort
rtal
alit
al
ityy in the
the
he high
hig
ighh adherence
adhe
ad
heere
rencce and
and hi
igh
g
safety
the
afety group
p aand
nd hhighest
ighe
ig
heest
s inn th
he lo
low
w ad
aadherence
here
he
rennce and
re
and low
low
o safety
saf
afet
etyy group,
et
grou
gr
o p, we
we observed
obse
ob
s rv
se
rved
ed significant
sig
igni
n ficant
attenuation of the combined effects of adherence to guidelines and safety matrices with outcomes
once adjusted for baseline confounding. This suggested that institutional case-mix accounted for
some of the variability in adherence to these matrices and in-hospital mortality relationship. In
fact, we found that patients with greater comorbidities (older age, females, diabetics, prior
congestive heart failure), high-risk presenting features (higher heart rate and signs of congestive
heart failure and lower systolic blood pressure and creatinine clearance), those admitted at
smaller non-teaching hospitals and cared for by non-cardiologists were less likely to meet these
standards and further that they were concentrated more in the lowest adherence quality and/or
12
DOI: 10.1161/CIRCULATIONAHA.114.013451
safety hospitals. This is consistent with previous studies that have also shown these features to be
associated with poor guideline-based therapies2,3,28-30 and poor patient safety.14,31 The Get With
The Guidelines investigators demonstrated a similar relationship between patient case-mix and
guideline-adherence and outcomes that had modest effect on hospital rankings in the pay-forperformance programs.24 Thus, all these and our studies suggest that there is relationship
between adherence to medications and safety matrices with hospital mortality. However, hospital
case-mix accounted for significant variation in adherence to these factors and thus its related
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
outcomes.
These findings may have some clinical and ‘quality’ implications. Our data suggest that
nstitutions that assess and monitor their quality of care inn the hope of im
mprovingg pa
atien
en
nt
institutions
improving
patient
outcomes should strike a balance and perhaps focus also on patient safety and not just use of
ev
vid
den
nce
ce-b
-bas
ba ed ttherapies.
hera
he
r pies. Best patient outcomess were
we achieved wh
w
en
n bboth
ot of these goals were
oth
evidence-based
when
acchiiev
e ed i.e. use
use of
of effective
eff
f eccti
tive
ve treatment
treat
reattme
mennt and
and in
in the right
riightt dose.
dosee. Thus,
dose
Thuus,
Th
us, doing
doin
do
i g the
in
th
he right
righht things
righ
thin
th
i gss and
in
and
achieved
doin
do
ingg them
in
t em
th
m right
right
ightt had
had the
thee best
besst chance
ch
han
ance
ce of
of being
bein
be
ingg associated
in
a soc
as
sociat
ci ted
d with
withh improved
impro
mpro
rove
veed patient
p ti
pa
tien
en
nt outcomes
ouutc
tcom
mes
es aand
nd
nd
doing
reprressen
ente
teed a better
be er surrogate
surrro
roga
gaate
t of
of ‘q
qua
uali
lity
li
ty’ rather
ty
rath
ra
t err than
th
tha
hann just
just
s guideline-based
gui
uide
deli
de
liine
ne-b
-bas
ased
as
ed therapies
the
herapies or
perhaps represented
‘quality’
safety alone. Strategies at measuring and improving both these aspects of patient related quality
should be implemented at all institutions as their association with outcomes was complementary.
Particularly, these strategies should be targeted at the at-risk group identified in our study i.e.
those at higher risk and those treated at smaller non-teaching institutions in order to achieve the
best institutional outcomes. Additionally, initiatives such as Pay-For-Performance8 as well the
American Heart Association policy recommendations32 helping to guide such programs should
recognize the importance of patient safety and amend their performance measures to include
patient safety along with compliance with guideline-based therapies while incentivizing
13
DOI: 10.1161/CIRCULATIONAHA.114.013451
institutions for better performance. In future, research efforts should be directed to explore
feasibility of developing a standardized composite matrix-incorporating both guideline
adherence and proper dosing of high risk medications that would have the best correlation with
outcomes.
Strengths and limitations
Although contemporary care may have changed since the CRUSADE data were collected, this
association is unique and has important policy implications. Participating hospitals were selfDownloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
selected for those interested in this national quality improvement initiative and may not be fully
representative of all community hospitals. Measures of safety were limited at this stage to
safety
appropriate initial dosing of antithrombotic agents. Expansion to a broader rangee off saf
afet
af
etyy
et
metrics would be highly desirable. Outcomes were limited to in-hospital clinical events as longterm
registry.
Finally,
although
erm
m outcomes
out
utco
co
ome
mes were
werre
we
re not collected in this registry
y. F
inally, althoug
gh wee aattempted
ttempted to adjust for a
tt
factors
and
hospital
bbroad
roaad range off patient-level
pat
atiient
ntt-l
- ev
evel
el clinical
cli
lini
nica
call fa
ca
fact
ctoors an
nd ho
ospittal
al ccharacteristics,
haracteeriist
stic
icss, tthe
he ppossibility
ossibi
ossi
b li
bi
lity
ty off
confounding
co
onf
n ou
ound
ndin
in
ng by unmeasured
unme
nmeasure
redd covariates
cova
co
vari
va
riaates
ri
atess remains.
rem
emai
ains
ns..
ns
Conclusions
Hospitals varied considerably in their use of NSTE ACS guideline-recommended treatments as
well as in the safe dosing of anti-thrombotic agents. There was low correlation between hospital
safety and adherence profiles. Overall guideline adherence and safety profiles were
independently associated with lower in-hospital bleeding and mortality rates. In-hospital
outcomes were better at centers that excelled at both safety and quality of care. These findings
supports the need for broader metrics of quality that should include not only measures of
compliance with guideline-based care but also that of hospital safety as promoted by the Institute
of Medicine.
14
DOI: 10.1161/CIRCULATIONAHA.114.013451
Funding Sources: CRUSADE was funded by Millennium Pharmaceuticals, Inc and Schering
Corporation with additional support from Bristol-Myers Squibb/Sanofi Pharmaceuticals
Partnership.
Conflict of Interest Disclosures: Dr. Mehta and Ms. Chen have no disclosures. Dr. Alexander
has modest research support from King Pharmaceutical and is on speakers bureau for Pfizer and
Amgen. Dr Ohman has research grants from Millennium Pharmaceuticals, Inc., Schering Corp.,
Bristol-Myers Squibb/Sanofi-Aventis Pharmaceuticals Partnership. Dr. Roe has research grants
from Millennium Pharmaceuticals, Inc., Schering Corp., Bristol-Myers Squibb/Sanofi-Aventis
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
Pharmaceuticals Partnership and is on their speaker bureau. Dr. Peterson has research grants
from Millennium Pharmaceuticals, Inc., Schering Corp., Bristol-Myers Squibb/Sanofi-Aventis
p
Pharmaceuticals Partnership.
References:
1.. E
ller
ll
erbe
er
beck
be
ck E
F,, JJencks
en
encks
SF, Radford MJ, Kresow
wik TF, Craig AS,
S, Gold
Gol
olld JA,
JA, Krumholz HM,
Ellerbeck
EF,
Kresowik
Vog
Vo
gel RA. Quality
gel
Qual
Qu
alit
itty of ccare
aree fo
ar
forr Me
Medi
d ca
di
care
re ppatients
atie
at
ient
ntss with
with acute
accut
utee myocardial
my
yoca
ocardi
ardial
al infarction:
inf
n ar
arct
cttio
ion:
n A four
n:
fou
ourr st
stat
ae
at
Vogel
Medicare
state
pi
ilo
ot study. The
he C
ooperaati
oop
tive
ve C
arddio
ar
diova
ovascculaar P
rojec
ect. JA
ec
JAMA
MA. 11995;273:1509-1514.
MA
9995;;27
273:
3 15509
3:
9-1
-151
5144.
pilot
Cooperative
Cardiovascular
Project.
JAMA.
2.. M
arci
ar
c ni
ci
niak
ak T
A, E
A,
lleerb
ll
erbeck E
F, R
adfo
ad
ford
rd M
J, K
reso
esowi
owik
ik T
F, G
o d JA
ol
JA,, Kr
Krum
umho
um
holz
ho
l H
lz
M, K
M,
iefe CI
I,
I,
Marciniak
TA,
Ellerbeck
EF,
Radford
MJ,
Kresowik
TF,
Gold
Krumholz
HM,
Kiefe
CI,
Allm
lmaan RM,
RM,
M Vogel
Vog
o el RA,
RA, Jencks
Jen
e ck
ckss SF.
SF Improving
Imprrov
ovin
ing the
th quality
quual
alit
ityy of care
caree fo
forr Me
M
dicaare
di
r ppatients
atieent
n s wi
with
th
Allman
Medicare
acute myocardial
myocar
ardi
d al
di
a infarction:
inf
nfar
arrcttio
on:
n results
ressul
ults
ts from
fro
om the
the Cooperative
Coop
Co
oper
op
errat
a iv
ve Cardiovascular
Card
Ca
rd
diov
o as
ascu
cula
cu
larr Project.
la
Proj
Pr
ojec
ect.
ec
t. JA
JAMA
M .
JAMA.
1998
19
98;2
;279
79:1
:135
3511-13
1357
57
1998;279:1351-1357.
3. Jencks SF, Cuerdon T, Burwen DR, Fleming B, Houck PM, Kussmaul AE, Nilasena DS,
Ordin DL, Arday DR. Quality of medical care delivered to Medicare beneficiaries: A profile at
state and national levels. JAMA. 2000;284:1670-1676.
4. Mehta RH, Montoye CK, Gallogly M, Baker P, Blount A, Faul J, Roychoudhury C, Borzak S,
Fox S, Franklin M, Freundl M, Kline-Rogers E, LaLonde T, Orza M, Parrish R, Satwicz M,
Smith MJ, Sobotka P, Winston S, Riba AA, Eagle KA; GAP Steering Committee of the
American College of Cardiology. Improving Quality of Care for Acute Myocardial Infarction:
The Guidelines Applied in Practice (GAP) Initiative. JAMA. 2002;287:1269-1276.
5. Mehta RH, Montoye CK, Faul J, Nagle DJ, Kure J, Raj E, Fattal P, Sharrif S, Amlani M,
Changezi HU, Skorcz S, Bailey N, Bourque T, LaTarte M, McLean D, Savoy S, Werner P,
Baker PL, DeFranco A, Eagle KA; American College of Cardiology Guidelines Applied in
Practice Steering Committee. Enhancing Quality of Care for Acute Myocardial Infarction:
Shifting the Focus of Improvement from Key Indicators to Process of Care and Tool Use:
15
DOI: 10.1161/CIRCULATIONAHA.114.013451
American College of Cardiology AMI GAP Project in Michigan: Flint and Saginaw Expansion. J
Am Coll Cardiol. 2004;43:2166-2173.
6. LaBresh KA, Ellrodt AG, Gliklich R, Liljestrand J, Peto R. Get with the guidelines for
cardiovascular secondary prevention: pilot results. Arch Intern Med. 2004;164:203-209.
7. Rogers WJ, Canot JG, Lambrew CT, Tiefenbrunn AJ, Kinkaid B, Shoultz DA, Frederick PD,
Every N. Temporal trends in the treatment of over 1.5 million patients with myocardial infarction
in U.S. from 1990 through 1999. The National Registry of Myocardial Infarction 1, 2, and 3. J
Am Coll Cardiol. 2000;36:2056-2063.
8. Centers for Medicare and Medicaid Services Website. Available at:
http://www.cms.hhs.gov/quality/hospital. Accessed April 14th, 2014.
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
9. Mehta RH, Peterson ED, Califf RM. Performance measures have a major effect on
cardiovascular outcomes: A review Am J Med. 2007;120:398-402.
10. Committee on Quality of Health Care in America. Crossing the Quality Chasm:
Chasm
m: A Ne
New
w
Health System for the 21st Century. Institute of Medicine, ed. Washington, DC: National
Nati
Na
t on
ti
nal
Academy Press; 2001.
11. Alexander KP,, Chen AY, Roe MT, Newby LK,, Gibson CM, Allen-LaPointe NM, Pollack C,
Gibler
Gibl
Gi
bler
bl
err WB,
WB, Ohman
Ohm
man EM, Peterson ED. Excess dosing
dos
o in
ng off antiplatelet
antiplateele
l t and
an
nd antithrombin
a tithrombin agents in
an
the
syndromes.
JAMA.
he treatments
tr
treatmen
nts of
of patients
p ti
pa
tien
en
nts with
wit
ithh non-ST-elevation
nonno
n ST
nST-e
-ele
leva
vati
tion
on aacute
cute ccoronary
oron
or
onarry sy
on
synd
ndro
rom
mes.. JA
AMA
M .
22005;294:3108-3116.
005;294:310
05
088-31
3 16
31
6.
12.
Maddox
TM,
Dai
Alexander
12
2. Ts
Tsai
a TT,
ai
TT, M
addox
dox TM
M, Roe
Ro MT,
MT, D
ai D, A
lexa
le
xaanderr KP,
KP, Ho
Ho PM,
PM, Messenger
Mess
Me
sssen
nge
g r JC,
JC
C, Nallamothu
Nalllaamo
Na
amothu
othuu
BK,
Contraindicated
BK
K, Peterson
Petters
Pe
rson
o ED,
ED,
D Rumsfeld
Rum
umsffel
eld JS;
JS; National
Na
al Cardiovascular
Car
ardi
dioovasccul
ular
ar Data
Dat
ataa Registry.
Reegi
gist
stry
ry. Co
Cont
ntra
rain
indica
cate
t d
coronary
medication use
use in
in dialysis
dial
di
allys
ysis patients
pat
atie
ient
ntss undergoing
nt
unde
un
derg
de
rgoi
rg
oing
oi
ng percutaneous
per
e cu
cuta
tane
neou
ne
ouss co
ou
coro
ronaary iintervention.
ro
nter
nt
erve
er
v nt
ve
n io
ion.
n. JA
JAMA.
2009;302:2458-2464.
2009
20
09;3
;302
02:2
:245
4588-24
2464
64
13. Hoekstra JW, Pollack CV Jr, Roe MT, Peterson ED, Brindis R, Harrington RA, Christenson
RH, Smith SC, Ohman EM, Gibler WB. Improving the care of patients with non-ST-elevation
acute coronary syndromes in the emergency department: The CRUSADE initiative. Acad Emerg
Med. 2002;9:1146-1155.
14. Bhatt DL, Roe MT, Peterson ED, Li Y, Chen AY, Harrington RA, Greenbaum AB, Berger
PB, Cannon CP, Cohen DJ, Gibson CM, Saucedo JF, Kleiman NS, Hochman JS, Boden WE,
Brindis RG, Peacock WF, Smith SC Jr, Pollack CV Jr, Gibler WB, Ohman EM; CRUSADE
Investigators. Utilization of Early Invasive Management Strategy for High-Risk Patients with
non-ST-segment elevation acute coronary syndromes: Results from the CRUSADE Quality
Improvement Initiative. JAMA. 2004;292:2096-2104.
15. Roe MT, Ohman EM, Pollack CV Jr., Peterson ED, Brindis RG, Harrington RA, Christenson
RH, Smith SC Jr, Califf RM, Gibler WB. Changing the model for care for patients with acute
coronary syndromes-implementing practice guidelines and altering physician behavior. Am
16
DOI: 10.1161/CIRCULATIONAHA.114.013451
Heart J. 2003;146:605-612.
16. The CRUSADE National Quality Improvement Website. Accessed on April 24th, 2008 at
http://www.CRUSADEQI.com.
17. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH,
Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE 3rd, Steward DE,
Theroux P, Gibbons RJ, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK,
Smith SC Jr; American College of Cardiology; American Heart Association. Committee on the
Management of Patients With Unstable Angina. ACC/AHA 2002 guideline update for the
management of patients with unstable angina and non-ST-segment elevation myocardial
infarction--summary article: a report of the American College of Cardiology/American Heart
Association task force on practice guidelines (Committee on the Management of Patients With
Unstable Angina). J Am Coll Cardiol. 2002;40:1366-1374.
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
18. Mehta RH, Roe MT, Chen AY, Lytle BL, Pollack CV Jr, Brindis RG, Smith SC Jr,
Harrington RA, Fintel D, Fraulo ES, Califf RM, Gibler WB, Ohman EM, Peterson ED. Recent
from
Trends in the Care of Patients With Non-ST Elevation Acute Coronary Syndrome:
e: IInsights
n ig
ns
ght
htss fr
fro
om
the
he Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adversee Outcomes
Ouutc
tcom
omes
om
es W
With
ith
Early Implementation of the ACC/AHA Guidelines (CRUSADE) Initiative. Arch
ch Intern
Int
nter
ernn Med.
Medd.
Me
2006;166:2027-2034.
199. Su
19.
Subh
Subherwal
bher
bh
erwa
er
wal S, Bach
wa
Bach RG, Chen AY, Gage BF
BF,
F, Ra
Rao SV, Newbyy LK
LK,, Wang
Wa TY, Gibler WB,
Ohman
Oh
hman EM
EM,
M, Roe
Roe MT
M
MT,, Po
P
Pollack
llac
ll
a k CV JJr.,
ac
r.,, Pe
r.
Pete
Peterson
ters
rson
on E
ED,
D Ale
D,
Alexander
lexa
xand
xa
n err K
nd
K.. Ba
Base
Baseline
seli
linne rrisk
li
issk of
o m
major
ajjor
bbleeding
leeedi
d ng in no
non-ST-segment
onn-ST
ST
T-ssegme
ment
me
nt eelevation
levaatiion m
leva
myocardial
yoccar
cardiaal infarction:
infaarc
arctio
ctio
on:: tthe
hee C
CRUSADE
RU
USA
ADE ((Can
Caan Ra
Rapi
Rapid
p d Ri
pi
Riskk
Stratification
Stra
St
ati
t ficationn of Un
U
Unstable
staablle A
Angina
ngin
ng
i a Pa
Patients
ati
tieent
ents S
Suppress
uppreesss A
Adverse
dveers
dv
erse Ou
Outcomes
utcomess With
With E
Early
arly
y
Implementation
mpl
plem
emen
em
enta
tati
ta
tion
ti
on ooff th
thee ACC/
A
ACC/AHA
CC//AH
AHA
A Gu
G
Guidelines)
idel
idel
elin
ines
in
e ) bl
es
bbleeding
eedinng
eed
ng sscore.
coree. C
co
Circulation.
irc
rccul
u atio
at on. 22009;119:1873-1882.
009;
00
9;11
9;
119:11873
11
1873
7 - 18 82
20. Liang KY,
KY
Y, Zeger
Z ge
Ze
gerr SL.
SL Longitudinal
Long
Lo
n it
itud
u in
ud
inall data
dat
ataa analysis
anal
an
a ys
al
ysis
is using
usiing generalized
gen
ener
eral
er
a izzed llinear
inea
in
earr mo
ea
mode
dels
de
ls. Biometrika
ls
a
models.
1986
19
86;7
;73:
3:13
13-22
22
1986;73:13-22.
21. Chin CT, Chen AY, Wang TY, Alexander KP, Mathews R, Rumsfeld JS, Cannon CP,
Fonarow GC, Peterson ED, Roe MT. Risk adjustment for in-hospital mortality of contemporary
patients with acute myocardial infarction: The acute coronary treatment and intervention
outcomes network (action) registry-get with the guidelines (gwtg) acute myocardial infarction
mortality model and risk score. Am Heart J. 2011;161:113-122.
22. Boersma E, Pieper KS, Steyerberg EW, Wilcox RG, Chang WC, Lee KL, Akkerhuis KM,
Harrington RA, Deckers JW, Armstrong PW, Lincoff AM, Califf RM, Topol EJ, Simoons ML.
Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment
elevation results from an international trial of 9461 patients. Circulation. 2000;101:2557-2567.
23. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van Der Werf F,
Avezum A, Goodman SG, Flather MD, Fox KAA. Predictors of hospital mortality in the Global
Registry of Acute Coronary Events. Arch Intern Med. 2003;163:2345-2353.
17
DOI: 10.1161/CIRCULATIONAHA.114.013451
24. Mehta RH, Liang L, Karve AM, Hernandez AF, Rumsfeld JS, Fonarow GC, Peterson ED.
Influence of Patients Case-mix on Hospital Process Performance Rankings and Eligibility for
Financial Incentives. JAMA. 2008;300:1897-1903.
25. Faxon DP, Schwamm LH, Pasternak RC, Peterson ED, McNeil BJ, Bufalino V, Yancy CW,
Brass LM, Baker DW, Bonow RO, Smaha LA, Jones DW, Smith SC Jr, Ellrodt G, Allen J,
Schwartz SJ, Fonarow G, Duncan P, Horton K, Smith R, Stranne S, Shine K; American Heart
Association's Expert Panel on Disease Management. Improving quality of care through disease
management: principles and recommendations from the American Heart Association's Expert
Panel on Disease Management. Circulation. 2004;109:2651-2654.
26. Institute of Medicine 1999. To Err is Human: Building a Safer Health System. Washington,
DC. National Academic Press, 1999.
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
27. Joint Commission on Accreditation of Healthcare Organization. Accessed April 24th, 2006 at
http://www.jointcommission.org.
28. Rathore SS, Mehta RH, Wang Y, Radford MJ, Krumholz HM. Age and quality
ty ooff ca
care
re
provided to elderly patients with acute myocardial infarction. Am J Med. 2003;114:307-315.
2003;1
114:3
14:3
307
07-3
-3
315
15..
29. Mehta RH, McCargar PA, Eagle KA, Stalhandske EJ. Quality of care in elderly diabetic
patients with acute myocardial infarction. Arch Intern Med. 2000;160:1301-1306.
30
0. Ohman
Oh
EM, Roe
R e MT,
Ro
M , Smith
MT
S it
Sm
ithh SC,
S , Jr,
SC
Jr, Brindis
Brin
Br
indi
diss RG,
RG Christenson
Ch
hri
rist
sten
st
e soon RH,
RH, Harrington
H rrin
Ha
ingt
gton
gt
on RA,
RA,, Gibler
Gib
ble
lerr
30.
EM,
WB,, Peterson
WB
nE
ED;
D; CRUSADE
CRU
RUSA
SADE
SA
DE Investigators.
Invvesti
es igaatorss. C
Care
aree ooff nnon-ST-elevation
on-S
on-S
ST-el
T-elev
evat
atio
ionn pati
ppatients:
atiien
nts
ts:: in
insi
insights
s gh
si
ghtss ffrom
ro
om
the
he C
CRUSADE
RUSAD
ADE national
nattion
na
nall qua
quality
uaalitty
ty iimprovement
mp
pro
rove
veemennt
nt init
initiative.
tiativ
ive.
e. Am H
Heart
ea
artt J. 2004;148
200
0004;
4;14
1448 (5 Suppl):S34-39.
Supp
uppl)):S344-39
31. Mehta
Meht
Me
htaa RH,
RH Alexander
A ex
Al
exan
anderr JH,
JH
H, Van
Van de Werf
Wer
erff F, Armstrong
Armsttron
ongg PW,
PW Pieper
Piiep
eper
er K
KS,
S, G
Garg
argg J,
ar
J C
Califf
alifff RM
al
RM,
Granger CB.. Relationship
Rela
Re
laati
t on
o sh
ship
p of
of incorrect
inco
in
corr
co
rrec
e t dosing
ec
dosi
do
s ng of
si
of fibrinolyic
fib
ibri
r nooly
ri
lyic
ic therapy
the
hera
rapyy and
ra
and cclinical
liini
n ca
call ou
outc
tcom
tc
o es.
outcomes.
JAMA
JA
JAMA.
MA 2005;293:1746-1750.
200
005;
5;29
293:
3:17
1746
46-175
17500
32. Bufalino V, Peterson ED, Burke GL, LaBresh KA, Jones DW, Faxon DP, Valadez AM,
Brass LM, Fulwider VB, Smith R, Krumholz HM, Schwartz JS; American Heart Association's
Reimbursement, Coverage, and Access Policy Development Workgroup. Payment for quality:
guiding principles and recommendations: principles and recommendations from the American
Heart Association's Reimbursement, Coverage, and Access Policy Development Workgroup.
Circulation. 2006;113:1151-1154.
18
DOI: 10.1161/CIRCULATIONAHA.114.013451
Table 1. Patient and hospital Features by hospital adherence and safety performance quartiles.
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
Variable
Demographics
Age (years)*
Female sex (%)
African American (%)
Insurance Status
HMO/private (%)
Medicare (%)
Medicaid
edicaid (%)
f/none (%)
Self/none
Past Medical History
pertension (%)
Hypertension
abetes mellitus (%)
Diabetes
perlipidemia (%)
Hyperlipidemia
rrent/Re
Rece
c nt
n smoking
smo
oki
king ((%)
%))
Current/Recent
orr MII (%)
(%)
Prior
or CHF
CHF (%
(%)
Prior
or PCI
CI (%)
Prior
or CABG
C BG (%)
CA
Prior
or stroke
stro
tr ke (%)
Prior
enti
en
nt ngg Features
Presenting
G Findings
F nd
Fi
ndin
din
i gs
ECG
ST Depression
Dep
epre
ress
re
ssio
ss
ionn (%
io
((%))
Transient
Tran
Tr
ansi
sien
entt ST elevation
ele
leva
vati
tion
on ((%)
%))
sitive cardiac mar
rkeers
r ((%)
%)
Positive
markers
Signs
g s of CHF ((%)
gn
%))
Heart rate (beats/min)*
Systolic BP (mmHg)*
CrCl (cc/min)†
Hospital Features
Cardiology care (%)
Total hospital beds*
PCI/CABG capabilities (%)
Teaching hospital‡ (%)
Low Adherence and Safety
(n = 9,560)
Low AdherenceHigh Safety (n = 7,315 )
High AdherenceLow Safety (n = 9,716)
High Adherence and Safety
(n = 12,700)
68 (56, 78)
39.3
9.1
66 (56, 77)
36.1
7.9
66 (55, 78)
39.4
11.8
65 (55, 76)
35.2
8.2
45.0
41.7
4.8
5.6
44.4
43.3
2.8
7.8
45.7
43.1
4.6
5.8
46.9
39.9
3.55
3.
77.3
7.
3
69.7
33.8
47.9
26.0
25.8
15
5.6
15.6
19
9.11
19.1
188 1
18.1
88.6
8.
6
68.9
32.0
50.4
28
8.9
28.9
24.6
6
24.6
113.7
13
.77
222.0
22
.00
19
.8
19.8
9.44
72.3
32.0
54.9
30.1
1
300.77
30.7
15
5.5
15.5
2 .99
20
20.9
17
.22
17.2
9.4
67
67.6
30.6
55.0
30.7
28.6
13
3.1
13.1
2 .22
22
22.2
19
9.1
19.1
88.5
8.
5
32.3
32
2.33
5.33
5.
994.1
94
.11
22.3
22
.3
3
84 (71, 100)
143 (122, 164)
53.1 (35.1, 74.6)
30.1
30
.11
7.22
7.
92
2.0
0
92.0
19.3
19
.3
3
82 (70,97)
146 (127, 166)
58.0 (39.3, 78.5)
34.9
34
4.99
7.00
7.
95.2
95
.2
224.4
24
.4
4
82 (70, 98)
146 (125, 166)
56.4 (37.6, 78.5)
32.9
32
.9
6.66
6.
95.0
19.4
81 (69, 95)
146 (127, 168)
59.8 (41.2, 80.2)
52.2
339 (202, 500)
70.8
39.4
56.3
370 (229, 478)
71.3
6.8
59.8
377 (281, 585)
92.5
40.6
70.0
400 (270, 536)
87.8
26.9
Data are expressed as percentages except for continuous variables* expressed as medians (25th, 75th percentiles); †Determined with Crockcroft-Gault formula; ‡Member of the Council of Teaching
Hospitals; BP = blood pressure; CABG = coronary artery bypass grafting; CHF = congestive heart failure; CrCl= creatinine clearance; ECG = electrocardiogram; HMO = health maintenance
organization; MI = myocardial infarction; PCI = percutaneous coronary intervention.
19
DOI: 10.1161/CIRCULATIONAHA.114.013451
Table 2. Treatment patterns by hospital safety–adherence performance quartiles
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
Variable
Acute Treatments
Aspirin (%)
Beta-blockers (%)
Heparin (overall) (%)
Unfractionated ((%))
Low molecular weight (%)
GP IIb/IIIa inhibitors(%)
Discharge
harge treatments
Aspirin
pirin (%)
Beta-blockers
ta-blockers (%)
ACE
E inhibitors
inhi
hibi
b to
ors (%)
%)
op
pid
idog
ogre
og
rell (%
re
(%))
Clopidogrel
Statins
tins
in
n (%
((%))
Excessive
s ivee Dosing*
ss
Anyy heparin
hepa
ep rin (%)
Unfractionated
U fr
Un
frac
ra tionated
d (%)
(%)
%
Low
Lo
ow mo
m
molecular
lecu
le
ula
larr we
w
weight
ight
ig
h ((%)
%)
GP IIIb/IIIa
Ib/I
/III
III
IIaa in
inhi
inhibitors
hibi
hi
b torss ((%)
bi
%)
Either
her any
any heparin
hep
epar
arin
ar
in or
or GP IIb/IIIa
IIb
Ib/I
/III
/I
IIaa (%)
II
(%)
Both
th excessive (%)
%)
Low Adherence and
Safety
(n = 9, 560)
Low AdherenceHigh Safety
(n = 7,315 )
High AdherenceLow Safety
(n = 9,716)
High Adherence
and Safety
(n = 12,700)
95.2
88.2
96.1
58.5
42.9
40.1
94.2
85.5
95.3
36.3
67.6
47.7
98.3
94.4
97.1
73.0
32.8
61.0
97.7
94.2
96.3
45.3
57.7
57
.77
66.2
66
.2
92.9
88.9
60.2
68.2
74.0
92.7
86.8
57.7
71.0
74
74.5
4.5
5
97.1
94.5
72.7
72
778.7
78
.7
86.1
86
97.2
94.6
69.9
80.4
86.6
6
32.1
3 .1
32
42.1
4 .1
42
117.9
17
.9
.9
29
29.8
.8
8
42.1
42.11
10.9
1 .99
10
17.4
17.
74
28.3
28.3
8.3
12.3
12
.
.3
25
25.8
.8
8
33.4
33.44
5.1
5..1
28.6
28.66
28
33.5
33.5
33
115.2
5.2
2
28.5
28
5
38.9
38.99
8.5
8.5
21.3
21.
1.33
332.9
2.9
.9
12
12.6
.6
.6
23
23.9
.9
9
32.7
32.77
6.0
*Among
ng patients
pat
atie
ient
ntss wi
with
without
thou
outt do
docu
documented
cume
ment
nted
ed ccontraindications.
ontr
on
trai
aind
ndic
icat
atio
ions
ns. Da
Data
ta aare
re eexpressed
xpre
xp
ress
ssed
ed aass pe
perc
percentages;
rcen
enta
tage
ges;
s; A
ACE
CE = aangiotensin-converting
ngio
ng
iote
tens
nsin
in-ccon
onve
vert
rtin
ingg en
enzy
enzyme;
zyme
me;; G
GP
P = gl
glyc
glycoprotein.
ycop
opro
rote
tein
in. Ot
O
Other
t
abbreviations as in Table 1; †Excess dose: Low molecular weight heparin Enoxaparin > 1.05 mg/kg; Unfractionated IV heparin - Infusion dose (>15 units/kg/hr)
or bolus dose (>70 units/kg) GP IIb/IIIa inhibitor - full dose of tirofiban if CrCl <30 cc/min or full dose of eptifibatide if CrCl <50 cc/min.
20
DOI: 10.1161/CIRCULATIONAHA.114.013451
Table 3. Unadjusted and adjusted in-hospital mortality by adherence and safety quartile groups
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
Hospital Quartile
Adherence Quartile Comparison
1 (highest) versus 2
1 versus 3
1 versus 4 (lowest)
Dosing Safety Quartile Comparison
1 (highest)
g
) versus 2
1 versus
ersus 3
ersus 4 (lowest)
1 versus
Duall Adherence and Safety Quartile
mparison (versus both low)
Comparison
Low
w Adherence and High Safety
gh Ad
dhe
hereence an
and L
ow Sa
S
fety
High
Adherence
Low
Safety
thh Ad
Adhe
here
he
renc
re
ncee an
nc
and Sa
Safe
afety
t High
ty
Both
Adherence
Safety
Unadjusted In-hospital Mortality
OR
95% CI for OR
P-value
Adjusted In-hospital Mortality
OR
95% CI for OR
P-value
1.01
0.86
0.55
0.82 - 1.25
0.68- 1.08
0.42- 0.73
0.921
0.201
<0.001
1.05
0.93
0.82
0.86 - 1.30
0.74 - 1.17
0.65- 1.05
0.629
0.538
0.111
0.86
0.77
0.69
0.65 - 1.13
0.59 - 1.00
0.51 - 0.93
0.265
0.052
0.016
0.78
0.82
0.80
0.62 - 1.00
0.64 - 1.05
1.0
. 5
0.661 - 1.04
1.044
0.61
0.046
0.109
0 10
0.
0 09
0.
0
0.098
0.81
0.69
0.58
0.59-1.11
0.53 – 0.8
.89
0.89
0.46- 0.74
74
0.184
0.004
<0.001
0.95
0.866
0.83
83
0.72 - 1.24
0.68 - 1.08
0.68 - 1.01
0.68
0.689
0.19
0.192
0.06
0.065
Tablee 4. Un
Unadjusted
U
adjusted
d and
and
d adjusted
adjjuste
ste
tedd in-hospital
in
n-hos
ospi
spi
pita
tall major
ta
m jo
ma
jorr bleeding
b eedi
bl
eding
ng by
by adherence
ad
dherence
e e and
an
nd safety
s fe
sa
fety
ty quartile
qua
uart
rtil
rt
ilee gr
il
ggroups
oups
u
Hospital
H
Ho
sp
pittal Q
Quartile
uaartil
til
ie
Adherence
ereenc
ncee Quartile
Quar
Qu
a ti
ar
tile Comparison
Com
ompa
pari
riso
ison
n
1 (highest)
high
hi
ghes
gh
est)
es
t) vversus
ersu
er
suss 2
su
ersus 3
1 versus
1 versus
ersu
er
suss 4 (l
(low
(lowest)
owes
est)
t)
Dosing Safety Quartile Comparison
1 (highest) versus 2
1 versus 3
1 versus 4 (lowest)
Dual Adherence and Safety Quartile
Comparison (versus both low)
Low Adherence and High Safety
High Adherence and Low Safety
Both Adherence and Safety High
Unadjusted
Una
n djjus
u te
ted In-hospital
In-h
hospital
s
l Major
M jo
Ma
or Bleeding
B eeeding
Bl
i
OR
95%
5% CI
C for
for OR
OR
P-value
P valu
Pva
al e
Adjusted
Bleeding
Adjus
u te
t d In-hospital
In-h
n-hos
o pita
it l Major
Major Bl
leedin
e
OR
O
995%
95
% CII for
for
o OR
OR
P-value
P
-va
v l
11.15
.15
15
1 10
1.
1
1.10
11.23
23
00.94
.94
94 - 11.40
.40
40
0.9900 1.34
1..34
0.901.001 00 1.50
1 50
00.190
.190
190
0.3341
0.341
0.048
0 04
0488
11.14
.14
14
1.2
.200
1.20
11.27
27
00.95
.95
95 - 11.38
.38
38
1 01 - 1.42
1.
1.442
1.01
11.0404 11.54
54
00.164
.16
16
0.044
0.044
00.017
01
0.86
0.63
0.63
0.71 - 1.04
0.51 - 0.77
0.51 - 0.77
0.128
<0.001
<0.001
0.89
0.72
0.81
0.73 - 1.08
0.60- 0.88
0.67 - 0.97
0.246
0.001
0.026
0.69
1.16
0.76
0.56-0.85
0.96 – 1.40
0.64- 0.91
<0.001
0.134
0.002
0.81
1.20
0.94
0.67 – 0.98
1.01 - 1.42
0.80- 1.11
0.027
0.036
0.460
21
DOI: 10.1161/CIRCULATIONAHA.114.013451
Figure Legends:
Figure 1. Association between hospital overall guidelines adherence and appropriate
Antithrombotic Dosing. Each + = one institution, crosshairs denote median values.
Figure 2. A. Unadjusted in-hospital mortality rates by hospital adherence and safety quartiles. B.
Unadjusted major bleeding rates by hospital adherence and safety quartiles
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
22
Overall
O
verall guideline
guuiddeline adherence (%)
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100
90
80
0
70
0
60
10
20
30
40
50
60
70
Appropriate
A
ppropriate Antithrombotic
Antithrombotic dosing
dosing (%)
(%)
Figure 1
80
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
Figure 2A
Downloaded from http://circ.ahajournals.org/ by guest on September 30, 2016
Figure 2B
Doing the Right Things and Doing Them the Right Way: The Association Between Hospital
Guideline Adherence, Dosing Safety, and Outcomes Among Patients with Acute Coronary
Syndrome
Rajendra H. Mehta, Anita Y. Chen, Karen P. Alexander, E. Magnus Ohman, Matthew T. Roe and
Eric D. Peterson
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Circulation. published online February 16, 2015;
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