Download Use of intensive lipid-lowering therapy in patients hospitalized with

Use of intensive lipid-lowering therapy in patients
hospitalized with acute coronary syndrome: An
analysis of 65,396 hospitalizations from 344 hospitals
participating in Get With The Guidelines (GWTG)
Usman Javed, MD, a Prakash C. Deedwania, MD, a Deepak L. Bhatt, MD, MPH, b Christopher P. Cannon, MD, b
David Dai, PhD, c Adrian F. Hernandez, MD, MHS, c Eric D. Peterson, MD, MPH, c and Gregg C. Fonarow, MD d
Fresno and Los Angeles, CA; Boston, MA; and Durham, NC
Objectives The study aimed to analyze the use of intensive lipid-lowering therapy (LLT) at discharge in a broad
population of patients hospitalized with acute coronary syndrome (ACS).
Background Early and intensive statin therapy in ACS was shown to reduce cardiovascular morbidity and mortality.
Utilization and predictors of LLT among hospitalized ACS patients are not known.
Methods The GWTG database was analyzed for ACS-related hospitalizations from 2005 to 2009. The use of LLT (defined
as dose of statin or combination therapy likely to produce N50% reductions in low-density lipoprotein [LDL]) and less intensive LLT
at discharge was assessed. Baseline characteristics and temporal trends in LLT were compared in these 2 treatment groups.
Results
Of 65,396 patients receiving LLT, only 25,036 (38.3%) were treated with an LLT regimen. Mean total cholesterol,
LDL, and triglycerides were significantly higher in the LLT group. Even among those with LDL N130 mg/dL, 50% or less received
LLT. Predictors of LLT at discharge included LLT before admission, hyperlipidemia, prior coronary artery disease, increasing
body mass index, and in-hospital percutaneous coronary intervention. Although there was some temporal improvement in the
rate of LLT from 2005 to 2007, a decline in use of LLT was noted in 2008 and 2009. This was attributed to a sharp reduction in
use of ezetimibe in combination with statin, without corresponding increases in intensive statin monotherapy.
Conclusions In a large cohort of patients admitted with ACS, most of the eligible patients were not discharged on LLT.
These data suggest the need for better implementation of guideline-recommended intensive statin therapy in patients with ACS.
(Am Heart J 2010;160:1130-1136.e3.)
Several large studies have consistently demonstrated
that lipid-lowering therapy (LLT) with 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitors (statins)
reduce cardiovascular risk irrespective of underlying
coronary artery disease (CAD).1 In patients with stable
CAD and acute coronary syndrome (ACS), statin therapy
has shown a reduction in mortality and recurrent cardiac
From the aUniversity of California, San Francisco-Fresno Medical Education Program,
Fresno, CA, bVA Boston Healthcare System and Brigham and Women's Hospital, Harvard
Medical School, Boston, MA, cDuke University Medical Center, Durham, NC, and
d
University of California, Los Angeles School of Medicine, Los Angeles, CA.
Guest Editor: Vera Bittner, MD, MSPH.
Submitted May 6, 2010; accepted August 24, 2010.
Reprint requests: Prakash C. Deedwania, MD, Cardiology Section, UCSF Program at
Fresno, 2615 E. Clinton Avenue (111), Fresno, CA, 93703.
E-mail: [email protected]
0002-8703/$ - see front matter
Published by Mosby, Inc.
doi:10.1016/j.ahj.2010.08.041
events.2-6 These data have established a very early clinical
benefit that persisted on long-term follow-up. The PROVE
IT-TIMI 225 and MIRACL6 trials have shown even better
clinical outcomes with early and intensive statin therapy
in ACS. It is also well established that the adherence to the
use of statin therapy in the post-ACS patient is directly
related to statin initiation during the index admission.7
In light of above the evidence, the recent National
Cholesterol Education Program Adult Treatment Panel
guideline update recommended an optional low-density
lipoprotein (LDL) treatment goal of b70 mg/dL for
patients with ACS.8,9 Moreover, the current guidelines
of the American College of Cardiology/American Heart
Association (ACC/AHA) recommend measurement of
lipid levels on admission and instituting LLT before
hospital discharge in patients with ACS.10,11
The objective of our study was to assess the use of LLT
at time of discharge in patients admitted with ACS along
with patient and hospital characteristics associated with
American Heart Journal
Volume 160, Number 6
use of LLT. This study analyzed data from the hospitals
participating in AHA's GWTG-CAD program from 2005 to
2009. Temporal trends in use of LLT were also assessed.
In patients admitted with ACS, prescription of various
LLTs (various agents and their prescribed doses) at time
of the hospital discharge was also assessed in relation to
the patients' admission lipid profile with the probability
of achieving LDL goal of b100 mg/dL and LDL b70 mg/dL.
Methods
GWTG-CAD is a national initiative of the AHA to promote
guidelines adherence in management of hospitalized patients
with coronary artery disease. The data collection process used in
this study and quality control features have been previously
described.12 All participating institutions were granted waiver of
informed consent by their local institutional review boards. The
Duke Clinical Research Institute (Durham, NC) serves as the data
analysis center and has an agreement to analyze the aggregate
de-identified data for research purposes. The GTWG program is
supported by the American Heart Association in part through an
unrestricted education grant from the Merck Schering Plough
Partnership that did not participate in the design, analysis,
preparation, review, or approval of the manuscript. The authors
are solely responsible for the design and conduct of this study,
all study analyses, the drafting and editing of the paper and its
final contents.
Study population
This study was drawn from 159,713 admissions with the
diagnosis of ACS (including ST-segment elevation myocardial
infarction [STEMI], non-STEMI [NSTEMI], and unstable angina),
between July 2005 and December 2009, from 410 participating
hospitals across the United States. Patients were excluded if they
left against medical advice, discontinued care, died, or were
discharged to a federal hospital, hospice, or another acute care
hospital. Of the 138,216 patients discharged, 119,387 (86.4%)
were receiving LLT and 14,279 (10.3%) were discharged
without LLT. Lipid-lowering therapy was contraindicated in
4,550 (3.3%). Of patients discharged on LLT, 53,991 admissions
were also excluded because the details describing agent/dose
was missing. The data from 65,396 admissions at 344 sites were
complete for the purposes of this analysis and formed the final
study population. Appendix Table 1A (online) shows the
characteristics of patients included and excluded from the
study population.
Lipid-lowering therapy
Lipid-lowering therapy was defined as therapy likely to
achieve a b50% reduction in LLT and included atorvastation 40
or 80 mg, rosuvastatin 20 or 40 mg, simvastatin 80 mg, or any
statin of any dose used in combination with ezetimibe (statin/
ezetimibe). All other LLTs were considered as less intensive
(LLLT). A secondary analysis excluding ezetimibe and statin
combination was performed to assess use and trends in intensive
statin monotherapy.
Data collected included patient demographics, pertinent
medical history, symptoms on arrival, laboratory results, inhospital treatment and procedures, discharge treatment, risk
Javed et al 1131
factor counseling, and patient disposition. The lipid levels
obtained within the first 24 hours of hospitalization were
measured at the local hospital laboratory. Yearly trends in
admission lipid values and LLT were assessed from 2005 to 2009.
Statistical analysis
Patients were divided into the LLT and LLLT categories as
defined above. In addition, LLT rate were noted in various
subgroups based on admission LDL and high-density lipoprotein
(HDL). In the descriptive analysis, the mean (±SD) and
percentages were reported for continuous and categorical
variables, respectively. For comparison of baseline characteristics in LLT and LLLT groups, Wilcoxon rank-sum tests were
used for continuous variables and χ2 tests for categorical
variables. In examining the association between LDL and LLT,
a multivariable logistic regression was used. The generalized
estimating equation (GEE) method with exchangeable working
correlation structure was used to account for within-hospital
clustering because patients at the same hospital are more likely
to have similar responses relative to patients in other hospitals
(ie, within-center correlation for response). The method
produces estimates similar to those from ordinary logistic
regression, but the estimated variances of the estimates are
adjusted for the correlation of outcomes within each hospital.
The variables entered into the model are patient age, gender,
race, body mass index, cardiovascular risk factors (smoking,
hypertension, hyperlipidemia, diabetes mellitus, renal insufficiency, prior MI stroke, heart failure, LLT before admission), and
type of ACS. A sensitivity analysis (28,724 subjects at 76 sites),
confined to the centers with N70% statin medication dose
reporting compliance, was used to exclude any selection bias in
the primary analysis. A P value of b.05 was considered
significant for the test of each variable. All analyses were
performed using SAS software (version 9.2, SAS Institute, Cary,
NC) by the Duke Clinical Research Institute (Durham, NC).
Results
The clinical characteristics of the patient study population are shown in Table I. Admission diagnosis was MI in
91.7% patients, while the remaining patients had unstable
angina. There were 41.7% of patients who were receiving
LLT before the index ACS admission. Admission LDL levels
were assessed in 54,892 (83.9%) of patients. The
characteristics of patients with and without LDL levels
assessed are shown in Appendix Table 1B (online).
Patients without lipid testing during hospitalization were
more likely to have been receiving LLT before admission.
At hospital discharge, there were 25,036 (38.3%) patients
receiving LLT and 40,360 (61.7%) receiving LLLT. Patients
receiving LLT were younger, less likely to be female, and
had higher admission LDL levels (Table I). There were
30.0% of patients who received statin monotherapy,
whereas 8.2% received statin/ezetimibe. The characteristics of patients receiving statin monotherapy and those
receiving statin/ezetimibe combination are shown in
Appendix Table 2 (online). Among various statins, the
rate of use and dosage of various statins in LLT subgroup
are shown in Appendix Table 3 (online).
American Heart Journal
December 2010
1132 Javed et al
Table I. Baseline characteristics in intensive and less intensive LLT groups
Patient
characteristics
Age (y)
Female
Race/ethnicity
White
Black
Hispanic
Asian
Diagnosis
STEMI/non-STEMI
Unstable Angina
LLT taken before Admission
Prior myocardial infarction
Prior stroke
Peripheral vascular disease
Hypertension
Diabetes—IDDM
Diabetes—NIDDM
Hyperlipidemia
Smoking (current or prior 1 y)
β-Blockers
ACE inhibitors
ARBs
Aspirin
Clopidogrel
Warfarin
Nitrates
Calcium channel blockers
Aldosterone blockers
Total cholesterol (mg/dL)
LDL cholesterol (mg/dL)
HDL cholesterol (mg/dL)
Triglycerides (mg/dL)
Overall (N = 65 396)
Intensive LLT (n = 25 036)
Less intensive LLT (n = 40 360)
P value
64.7 ± 13.9
34.3%
62.6 ± 13.4
32.2%
66.0 ± 14.1
35.6%
b.001
b.001
72.3%
7.0%
6.4%
2.8%
71.4%
7.7%
6.2%
2.9%
72.9%
6.5%
6.5%
2.8%
b.001
b.001
.149
.220
91.7%
8.3%
41.7%
19.9%
8.2%
8.1%
67.8%
9.3%
15.9%
55.7%
33.5%
97.7%
72.9%
12.5%
98.2%
80.8%
10.5%
27.0%
9.0%
3.6%
170.1 ± 48.2
103.4 ± 40.0
38.1 ± 12.4
155.4 ± 124.7
92.4%
7.6%
44.4%
21.0%
7.5%
8.0%
67.5%
9.9%
15.9%
58.7%
35.8%
98.1%
75.5%
12.4%
98.6%
84.9%
10.2%
27.8%
8.4%
3.8%
174.6 ± 51.0
107.2 ± 43.0
37.9 ± 11.9
161.0 ± 128.1
91.4%
8.6%
40.0%
19.2%
8.6%
8.2%
67.9%
8.9%
15.9%
53.7%
32.0%
97.4%
71.2%
12.5%
98.0%
78.3%
10.6%
26.6%
9.4%
3.5%
167.1 ± 46.2
101.0 ± 37.7
38.3 ± 12.7
151.8 ± 122.3
b.001
b.001
b.001
b.001
b.001
.341
.319
b.001
.993
b.001
b.001
b.001
b.001
.724
b.001
b.001
.187
b.001
b.001
.066
b.001
b.001
.254
b.001
ARB, Angiotensin receptor blocker; ACE, angiotensin converting enzyme; IDDM, insulin dependent diabetes mellitus; NIDDM, non-insulin dependent diabetes mellitus.
Table II. Use of intensive LLT at discharge based on admission HDL-C and LDL-C levels
LDL (mg/dL)
HDL (mg/dL)
b40 (n = 27 762)
40-60 (n = 14 589)
≥60 (n = 2 737)
Total (n = 45 088)
<70 (n = 9 157)
70-100
(n = 13 603)
100-130
(n = 11 918)
130-160
(n = 6 672)
≥160 (n=3 738)
Total
(n = 45 088)
13.29%
38.19%
5.70%
36.95%
1.31%
33.45%
20.31%
37.53%
18.71%
36.03%
9.55%
35.53%
1.92%
30.44%
30.17%
35.51%
16.15%
38.68%
8.73%
37.68%
1.56%
34.33%
26.43%
38.09%
8.76%
44.14%
5.28%
43.32%
0.76%
38.71%
14.80%
43.57%
4.66%
52.38%
3.10%
52.58%
0.53%
44.96%
8.29%
51.98%
61.57%
39.58%
32.36%
39.26%
6.07%
34.38%
100%
39.16%
Frequency missing 20,308. Numbers in bold denote the percentage of ACS hospitalizations in that cell that received intensive LLT at hospital discharge.
When the analysis was confined to 76 hospitals that
collected statin dose in N70% of patients (n = 28,724), the
findings were similar (39.3% on LLT, of which 33.1%
were on statin monotherapy). In comparison, the patients
without LLT dose documentation had lower rates of
prior LLT, diabetes, hyperlipidemia (lower total cholesterol, LDL cholesterol, and triglycerides), established
CAD, prior CABG or percutaneous coronary intervention
(PCI), and acute STEMI. These patients however had
higher prevalence of hypertension, PVD, prior MI or
American Heart Journal
Volume 160, Number 6
Figure 1
Javed et al 1133
unstable angina had a lower likelihood of receiving LLT
(Figure 1). There was a marginal impact of confining the
analysis to intensive statin monotherapy and center
reporting compliance on GEE model results. In the statin
monotherapy model, diabetes mellitus, prior PCI, and
prior CABG were additional independent predictors
of LLT.
Temporal trends in the use of LLT were also examined.
Lipid-lowering therapy rates since the publication of
updated National Cholesterol Education Program-ATP
guidelines in 2004 increased initially from 35.5% to
41.6% (2005 to 2007). However, an insignificant drop in
rate of LLT was noted with a decline to 35.7% by
December 2009. We found this to be primarily due to a
significant drop in the use of statin/ezetimibe combination from 11.4% in 2007 to 3.4% in 2009 (Table III).
When statin/ezetimibe combination was excluded as
LLT, less than one third of ACS patients was treated with
intensive statin monotherapy. Use of intensive statin
monotherapy at discharge was 28.0% in 2005 and 33.1%
in 2009, without significant change during the 2007 to
2009 period.
Discussion
Factors associated with LLT by multivariate GEE model.
cerebrovascular accident, and NSTEMI. The excluded
sites also had lower rates of revascularization (PCI or
CABG) and teaching hospitals.
Factors associated with LLT
A number of patient characteristics were more frequent
in patients discharged with LLT (Table I). Diagnosis of
STEMI, presence of ST changes/LBBB on admission ECG,
and PCI with or without stent, elevated total cholesterol,
LDL, and triglyceride values were more likely to be
discharged on LLT. There was no impact of uninsured
status, non–insulin-dependent diabetes mellitus, prior
CABG, or HDL between the 2 groups. Table II provides
the rates of LLT based on admission LDL and HDL levels.
Multivariate analysis of these data using the GEE model
demonstrated LLT before admission, history of CAD or
prior MI, hyperlipidemia, LDL per 10 mg/dL rise, body
mass index (BMI) increase by 5 units, PCI with stent
placement, and male gender as independent predictors of
LLT. Patients with increasing age, chronic dialysis, and
The present analysis shows that among hospitals
participating in GWTG-CAD, most hospitalized ACS
patients are not discharged on LLT. Even among those
with admission LDL N130 mg/dL, 50% or less received
LLT. During the first 3 years of observation in this study,
there was very modest improvement in LLT on discharge.
This trend did not persist, instead a decline in this
therapeutic approach was observed during 2008 to 2009.
Role of intensive LLT in ACS
Although statins play a pivotal role in LDL reduction,
they may also exhibit a pleotropic effect by decreasing
extent of myocardial ischemia, remodeling, as well as
promoting plaque stabilization and endothelial function.13-15 Based on these mechanistic properties, and as
demonstrated in several clinical studies, it is now widely
accepted that initiation of an early and intensive statin
therapy in ACS is associated with reduced inpatient
mortality and morbidity3,4,6,16 as well as improved longterm survival and lower rates of recurrent coronary
events. In the MIRACL trial, LLT with atorvastatin
80 mg/d (vs placebo) was started within 24 to 96
hours of presentation with ACS.6 It was associated with
a lower risk of symptomatic ischemia requiring emergent rehospitalization. This effect was independent of
baseline LDL level, although LDL was decreased from
126 to 72 mg/dL in the treatment group. The clinical
benefit started to exhibit at 4 weeks and then persisted
for the duration of the study. The PROVE-IT TIMI 22 trial
has further demonstrated that aggressive LLT in ACS,
with even lower targets LDL levels, leads to reduction in
American Heart Journal
December 2010
1134 Javed et al
Table III. Temporal trends of intensive LLT and intensive statin monotherapy
Year
Total
(N = 65 396)
2005
2006
2007
2008
2009
5283
15 520
18 082
17 143
9368
Intensive LLT overall
(n = 25 036)
1875
6108
7523
6188
3342
(35.49)
(39.36)
(41.60)
(36.10)
(35.67)
Yearly
trend P
Intensive statin
monotherapy (n = 19 645)
.039
.138
b.001
.221
revascularization and unstable angina.3,6 In PROVE-IT
TIMI 22, the median LDL was decreased to 62 mg/dL on
80 mg of atorvastatin in comparison to 95 mg/dL on
40 mg of pravastatin. Similar to the findings in the
MIRACL, the beneficial effects of high-dose statins
emerged as early as 30 days and then persisted during
the 2 years of follow-up.
Based on the available evidence, the revised Adult
Treatment Panel III guidelines has recommended an
early and LLT in patients admitted for ACS and has
included an optional therapeutic goal of LDL b70 mg/dL
in these high-risk patients.8,9 Our analysis shows that
despite available evidence and recommendations, in this
large cohort of hospitalized patient with ACS, 10.3% (n =
14,279) of patients with ACS were not discharged on
LLT. Moreover, only 38.2% of eligible patients were
discharged on LLT. Although LDL remains the primary
goal for therapeutic intervention, the LLT prescribed at
the time of discharge may also take HDL into consideration. The inverse relationship of HDL and with
nonfatal MI and cardiovascular-related death has been
demonstrated previously.17 The present study illustrates
that 61.6% of patients presenting with ACS have HDL
levels b40 mg/dL. To improve secondary prevention of
cardiovascular risk, it may be necessary to implement
additional lipid-modifying therapy (together with routine
statin therapy) targeting HDL N40 mg/dL in males and
N50 mg/dL in females.
Lipid measurement in hospitalized patients with ACS
Although the current guidelines recommend lipid
measurement in ACS, it is measured in less than half of
these patients in routine clinical practice.18 This practice
has been largely based on the convention that lipid levels
are unreliable in ACS settings and usually associated with
an initial decrement in total cholesterol and LDL.19
However, more recent data have shown less pronounced
changes in lipid profile.20 In this analysis, about half of
ACS patients had LDL b100 mg/dL, with LLT used in
about 36% of such patients. Although rate of LLT
increased with the rise in LDL, nearly half of patients
with LDL N160 mg/dL were still left untreated with LLT.
Thus, these patients had a low probability of achieving
target LDL in near future.
1422
4516
5467
5220
3020
(26.92)
(29.10)
(30.23)
(30.45)
(32.24)
Yearly
trend P
.448
.381
.204
.734
Ezetimibe plus
statin (n = 5391)
453
1592
2056
968
322
(8.57)
(10.26)
(11.37)
(5.65)
(3.44)
Yearly
trend P
.043
.202
b.001
.002
It is interesting to note that in our study, LLT was more
likely to be used in younger patients, male, smokers,
overweight patients, in those with STEMI and otherwise
those more likely to undergo PCI, and those with high
lipid levels. Ironically, patients with diagnosis of unstable
angina, prior stroke, heart failure, and renal insufficiency
were treated with less LLLT. Moreover, there was no
difference in the type of therapy in those with prior
CABG and non–insulin-dependent diabetes mellitus. The
present study demonstrates the underutilization of LLT in
the very high risk group, which is prone to recurrent
ischemic cardiovascular events.
Lipid-lowering therapy at discharge
The available evidence suggests better long-term
compliance and higher survival rates in ACS patients
initially discharged on statin therapy than those who
were not.7 Subsequently, the CRUSADE Quality Improvement Initiative also showed that the use of LLT at
discharge among select ACS patients increased from 78%
in 2000 to 88% in 2004.21 The overall low rate of LLT
observed in our analyses along with recent declines
during 2008 to 2009 are concerning and emphasize the
need for implementation of evidence-based and guideline-recommended therapy in most patients with ACS.
Although intensive statin monotherapy continued to
increase marginally, the drop-off in 2008 and 2009 in
intensive LLT was essentially due to the decrease in use
of ezetimibe in combination in statin therapy. However,
there was no offsetting increased use of intensive statin
therapy. These data represent interesting, but potentially
unfortunate consequences of the well-publicized ENHANCE trial controversy.22-25 In its aftermath, the
plethora of discussion raised further controversy about
even the proven benefits of statin therapy. This has had a
large impact on the contemporary practice of lipid
management without providing a clear alternative to
the use of ezetimibe. As a result, starting in 2008, fewer
ACS patients were treated with therapy that would allow
them to achieve LDL cholesterol goals recommended in
national guidelines. Despite the lower use of statin/
ezetimibe combination, there was little to no shift to highdose statin therapy (at least at time of hospital discharge).
These data underscore yet another impact on routine
American Heart Journal
Volume 160, Number 6
clinical practice heralded by safety or lack of efficacy
concerns as raised by some recent controversies.26,27
Nevertheless, ezetimibe alone or in combination with
statin therapy has not been proven to change outcomes
in ACS, so the full clinical implications of these treatment
shifts are not yet known.
Limitations
There is a potential for selection bias in this study
because discharge LLT dosing data were not available in
50% of patients. There were modest baseline differences
between those with and without discharge dosing of
lipid therapy recorded. These factors may influence the
generalizability of these findings. Furthermore, the
GWTG-CAD database is voluntary and therefore may
not be representative of the entire US practice. These
findings may not reflect care at hospitals that differ
substantially from participating hospitals. Registry hospitals tend to be larger than nonparticipating hospitals,
are more likely to be affiliated with a medical school, and
are more likely to have available facilities for cardiac
catheterization, PCI, and cardiac surgery. GWTG-CAD
participating hospitals also were provided with feedback
on performance that may have also influenced the care
patterns. The hospitals participating in the GWTG-CAD
program may be more likely to prescribe LLT, such that
the treatment gaps are even larger than what was
observed here. Hence, the data presented here might
reflect different and possibly higher rates of LLT than
actually prescribed among patients and hospitals that
differ from those participating in GWTG-CAD. Although
the lipid levels obtained in this study were measured in
the first 24 hours of admission, they may or may not be
entirely reflective of the baseline steady-state lipid levels.
Furthermore, we do not have data as to whether patients
were in the fasting state. This real-world study used
results of various commercially available lipid panel
assays rather than results from a single central core
laboratory. Although this methodology may introduce
great variability to lipid testing results, this approach
makes these findings more applicable to clinical
practice. This study only assessed LLT dosing at time of
hospital discharge. Some patients may have had subsequent change in dosing or modification of their lipid
therapy regimen as an outpatient. As the current
guidelines do not specify a dose of statin for ACS
patients but only a target of therapy (ie, optional target
of LDL b70 mg/dL in high risk patients), many clinicians
may believe that the titration to LLT can occur post
discharge, and this may explain the reason for the
treatment gap. The utilization of LLT at hospital
discharge does not necessarily indicate that patients
remained adherent to their discharge regimen. The
extent of dietary and exercise counseling were not
available in this study.
Javed et al 1135
Conclusions
During the period of 2005 to 2009, only about one
third of patients hospitalized with ACS were discharged
on LLT. Even among patients with documented admission LDL, which would require N50% reduction to
achieve an optional goal of LDL b70 mg/dL, only about
50% were discharged on LLT. Independent predictors of
LLT at discharge included LLT before admission, history
of hyperlipidemia or coronary artery disease, increasing
BMI and lipid level, and in-hospital percutaneous
coronary intervention. In addition, the rate of adopting
LLT in ACS decreased significantly over the last 2 years
because of a marked decline in the use of ezetimibe in
combination with statin therapy without an offsetting
increase in intensive statin monotherapy. These findings
underscore the importance of ongoing emphasis regarding implementation of current guidelines for measuring
lipids and intensive statin therapy in all ACS patients.
Disclosures
Dr Bhatt: research grants from Astra Zeneca, BristolMyers Squibb, Eisai, Ethicon, Heartscape, Sanofi Aventis
and the Medicines Company. Dr Deedwania: consultant/
advisory board of AstraZeneca and Pfizer. Dr Peterson:
research funding from Bristol Myers Squibb, Sanofi
Aventis partnership. Dr Cannon: research grants from
Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi
Partnership, Glaxo Smith Kline Intekrin Therapeutics,
Novartis, Takeda, clinical advisor and equity in Automedics Medical Systems. Dr Hernandez: research grant
from Johnson and Johnson, Merck, and honorarium from
AstraZeneca and Medtronic. Dr Fonarow: consultant/
advisory board to Merck Schering Plough and honorarium
from Abbott, AstraZeneca, Merck Schering Plough, and
Pfizer. Other authors have no disclosures.
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American Heart Journal
Volume 160, Number 6
Javed et al 1136.e1
Appendix
Table 1A. Patient characteristics of the study and excluded patients
Patient characteristics
Age (y)
Female
Race/ethnicity
White
Black
Hispanic
Asian
Diagnosis
STEMI/non-STEMI
Unstable angina
LLT taken before admission
Prior myocardial infarction
Prior stroke
Peripheral vascular disease
Hypertension
Diabetes—IDDM
Diabetes—NIDDM
Hyperlipidemia
Smoking (current or prior 1 y)
β-Blockers
ACE inhibitors
ARBs
Aspirin
Clopidogrel
Warfarin
Nitrates
Calcium channel blockers
Aldosterone blockers
Total cholesterol (mg/dL)
LDL cholesterol (mg/dL)
HDL cholesterol (mg/dL)
Triglycerides (mg/dL)
PCI with stent
CABG
Overall (n = 159 713)
Excluded (n = 94 317)
Study cohort (N = 65 396)
P value
66.2 ± 14.4
35.6%
67.3 ± 14.6
36.5%
64.7 ± 13.9
34.3%
b.001
b.001
70.6%
7.4%
5.6%
3.2%
69.4%
7.7%
5.1%
3.5%
72.3%
7.0%
6.4%
2.8%
b.001
b.001
b.001
b.001
93.6%
6.4%
94.9%
5.1%
91.7%
8.3%
b.001
b.001
20.1%
8.9%
8.7%
68.2%
8.2%
14.1%
51.3%
31.1%
96.9%
70.8%
12.2%
97.4%
75.6%
11.3%
17.8%
6.5%
3.7%
168.7 ± 48.2
102.1 ± 40.0
38.5 ± 12.7
152.9 ± 122.3
35.4%
7.5%
20.4%
9.6%
9.2%
68.6%
7.1%
12.3%
47.2%
29.5%
96.3%
68.8%
12.1%
96.7%
69.9%
12.4%
11.4%
4.7%
3.9%
167.5 ± 48.1
101.1 ± 40.1
38.8 ± 13.1
150.6 ± 120.0
25.1%
6.5%
19.9%
8.2%
8.1%
67.8%
9.3%
15.9%
55.7%
33.5%
97.7%
72.9%
12.5%
98.2%
80.8%
10.5%
27.0%
9.0%
3.6%
170.1 ± 48.2
103.4 ± 40.0
38.1 ± 12.4
155.4 ± 124.7
50.2%
8.7%
.042
b.001
b.001
.003
b.001
b.001
b.001
b.001
b.001
b.001
.043
b.001
b.001
b.001
b.001
b.001
.102
b.001
b.001
b.001
b.001
b.001
b.001
ARB, Angiotensin receptor blocker; ACE, angiotensin converting enzyme; IDDM, insulin dependent diabetes mellitus; NIDDM, non-insulin dependent diabetes mellitus.
Table 1B. Patient characteristics based on measurement of lipid levels
Patient characteristics
Overall (N = 65 396)
Lipids measured (n = 54 892)
Lipids not measured (n = 10 504)
P value
Age (y)
Female
Race/ethnicity
White
Black
Hispanic
Asian
Diagnosis
STEMI/non-STEMI
Unstable angina
LLT taken before Admission
Prior myocardial infarction
Prior stroke
Peripheral vascular disease
Hypertension
64.7 ± 13.9
34.3%
64.0 ± 13.8
33.6%
68.4 ± 13.9
38.0%
b.001
b.001
72.3%
7.0%
6.4%
2.8%
72.4%
7.1%
6.4%
2.4%
71.9%
6.3%
6.2%
5.0%
.290
.002
.427
b.001
91.7%
8.3%
41.7%
19.9%
8.2%
8.1%
67.8%
91.9%
8.1%
38.7%
18.9%
7.7%
7.6%
67.1%
91.1%
8.9%
57.2%
24.9%
10.9%
10.7%
71.4%
.008
.008
b.001
b.001
b.001
b.001
b.001
American Heart Journal
December 2010
1136.e2 Javed et al
Table 1B (continued)
Patient characteristics
Diabetes—IDDM
Diabetes —NIDDM
Hyperlipidemia
Smoking (current or prior 1 y)
β-Blockers
ACE inhibitors
ARBs
Aspirin
Clopidogrel
Warfarin
Nitrates
Calcium channel blockers
Aldosterone blockers
PCI with Stent
CABG
Intensive LLT
Intensive statin monotherapy
Statin/ezetimibe
Overall (N = 65 396)
Lipids measured (n = 54 892)
Lipids not measured (n = 10 504)
P value
9.3%
15.9%
55.7%
33.5%
97.7%
72.9%
12.5%
98.2%
80.8%
10.5%
27.0%
9.0%
3.6%
50.2%
8.7%
38.3%
30.0%
8.2%
8.4%
15.0%
55.2%
34.9%
97.9%
74.0%
12.0%
98.5%
82.2%
10.4%
26.8%
8.5%
3.4%
52.4%
8.6%
38.9%
30.8%
8.1%
13.7%
20.8%
58.2%
26.2%
96.3%
66.8%
15.1%
97.0%
73.5%
11.0%
28.1%
11.8%
4.7%
38.9%
9.0%
35.2%
26.2%
8.9%
b.001
b.001
b.001
b.001
b.001
b.001
b.001
b.001
b.001
.081
.008
b.001
b.001
b.001
.147
b.001
b.001
.004
Table 2. Patient characteristics in intensive LLT groups: overall, statin monotherapy, and ezetimibe plus any statin
Patient characteristics
Age (y)
Female
Race/ethnicity
White
Black
Hispanic
Asian
Diagnosis
STEMI/non-STEMI
Unstable angina
LLT taken before admission
Prior myocardial infarction
Prior stroke
Peripheral vascular disease
Hypertension
Diabetes—IDDM
Diabetes—NIDDM
Hyperlipidemia
Smoking (current or prior 1 y)
Total cholesterol (mg/dL)
LDL cholesterol (mg/dL)
HDL cholesterol (mg/dL)
Triglycerides (mg/dL)
Overall LLT (n = 25 036)
Statin monotherapy (n = 19 645)
Statin/ezetimibe (n = 5 391)
P value
62.6 ± 13.4
32.2%
62.4 ± 13.5
31.7%
63.6 ± 12.8
34.0%
b.001
.001
71.4%
7.7%
6.2%
2.9%
69.6%
8.1%
6.8%
3.1%
77.9%
6.3%
4.2%
2.2%
b.001
b.001
b.001
b.001
92.4%
7.6%
44.4%
21.0%
7.5%
8.0%
67.5%
9.9%
15.9%
58.7%
35.8%
174.6 ± 51.0
107.2 ± 43.0
37.9 ± 11.9
161.0 ± 128.1
93.5%
6.5%
41.3%
19.8%
7.3%
7.4%
66.3%
9.6%
15.6%
55.5%
37.3%
175.6 ± 49.9
108.5 ± 42.5
37.9 ± 11.9
158.8 ± 125.0
88.3%
11.7%
56.0%
25.2%
8.2%
10.0%
71.7%
11.1%
16.8%
70.0%
30.5%
170.8 ± 54.5
102.1 ± 44.6
38.1 ± 11.9
169.4 ± 138.4
b.001
b.001
b.001
b.001
.038
b.001
b.001
.002
.050
b.001
b.001
b.001
b.001
.085
b.001
Table 3. Specific lipid-lowering agents in treatment groups
Statin
Rosuvastatin
Stain dose
5 mg
10 mg
20 mg
40 mg
Overall
(N = 65 396)
649
2116
1156
417
Overall (%)
LLT (n = 25 036)
LLT (%)
0.99
3.24
1.77
0.64
31
85
1156
417
0.12
0.34
4.62
1.67
LLLT (n = 40 360)
618
2031
0
0
LLLT (%)
1.53
5.03
0.00
0.00
American Heart Journal
Volume 160, Number 6
Javed et al 1136.e3
Table 3 (continued)
Statin
Atovastatin
Simvastatin
Simvastatin/ezetimibe Combination
Statin/ezetimibe⁎
Stain dose
10 mg
20 mg
40 mg
80 mg
5 mg
10 mg
20 mg
40 mg
80 mg
10-10 mg
10-20 mg
10-40 mg
10-80 mg
Other
⁎ Ezetimibe and any dose of any statin in separate doses.
Overall
(N = 65 396)
Overall (%)
LLT (n = 25 036)
LLT (%)
LLLT (n = 40 360)
LLLT (%)
4122
5683
7331
7919
94
1086
6665
10 887
3589
153
1005
1815
603
131
1690
6.30
8.69
11.21
12.11
0.14
1.66
10.19
16.65
5.49
0.23
1.54
2.78
0.92
0.20
2.58
52
109
7331
7919
2
24
121
284
3589
153
1005
1815
603
131
1690
0.21
0.44
29.28
31.63
0.01
0.10
0.48
1.13
14.34
0.61
4.01
7.25
2.41
0.52
6.75
4070
5574
0
0
92
1062
6544
10 603
0
0
0
0
0
0
0
10.08
13.81
0.00
0.00
0.23
2.63
16.21
26.27
0.00
0.00
0.00
0.00
0.00
0.00
0.00