Use of intensive lipid-lowering therapy in patientshospitalized with acute coronary syndrome: Ananalysis of 65,396 hospitalizations from 344 hospitalsparticipating 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, MDd

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 broadpopulation 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 (definedas dose of statin or combination therapy likely to produce N50% reductions in low-density lipoprotein [LDL]) and less intensive LLTat 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 receivedLLT. Predictors of LLT at discharge included LLT before admission, hyperlipidemia, prior coronary artery disease, increasingbody mass index, and in-hospital percutaneous coronary intervention. Although there was some temporal improvement in therate 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 inuse 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 demonstratedthat lipid-lowering therapy (LLT) with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)reduce cardiovascular risk irrespective of underlyingcoronary artery disease (CAD).1 In patients with stableCAD and acute coronary syndrome (ACS), statin therapyhas shown a reduction in mortality and recurrent cardiac

From the aUniversity of California, San Francisco-Fresno Medical Education ProgramFresno, CA, bVA Boston Healthcare System and Brigham andWomen's Hospital, HarvardMedical School, Boston, MA, cDuke University Medical Center, Durham, NC, anddUniversity 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 aFresno, 2615 E. Clinton Avenue (111), Fresno, CA, 93703.E-mail: deed1@sbcglobal.net0002-8703/$ - see front matterPublished by Mosby, Inc.doi:10.1016/j.ahj.2010.08.041

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events.2-6 These data have established a very early clinicalbenefit that persisted on long-term follow-up. The PROVEIT-TIMI 225 and MIRACL6 trials have shown even betterclinical outcomes with early and intensive statin therapyin ACS. It is also well established that the adherence to theuse of statin therapy in the post-ACS patient is directlyrelated to statin initiation during the index admission.7

In light of above the evidence, the recent NationalCholesterol Education Program Adult Treatment Panelguideline update recommended an optional low-densitylipoprotein (LDL) treatment goal of b70 mg/dL forpatients with ACS.8,9 Moreover, the current guidelinesof the American College of Cardiology/American HeartAssociation (ACC/AHA) recommend measurement oflipid levels on admission and instituting LLT beforehospital discharge in patients with ACS.10,11

The objective of our study was to assess the use of LLTat time of discharge in patients admitted with ACS alongwith patient and hospital characteristics associated with

Javed et al 1131American Heart JournalVolume 160, Number 6

use of LLT. This study analyzed data from the hospitalsparticipating in AHA's GWTG-CAD program from 2005 to2009. Temporal trends in use of LLT were also assessed.In patients admitted with ACS, prescription of variousLLTs (various agents and their prescribed doses) at timeof the hospital discharge was also assessed in relation tothe patients' admission lipid profile with the probabilityof achieving LDL goal of b100 mg/dL and LDL b70 mg/dL.

MethodsGWTG-CAD is a national initiative of the AHA to promote

guidelines adherence in management of hospitalized patientswith coronary artery disease. The data collection process used inthis study and quality control features have been previouslydescribed.12 All participating institutions were granted waiver ofinformed consent by their local institutional review boards. TheDuke Clinical Research Institute (Durham, NC) serves as the dataanalysis center and has an agreement to analyze the aggregatede-identified data for research purposes. The GTWG program issupported by the American Heart Association in part through anunrestricted education grant from the Merck Schering PloughPartnership that did not participate in the design, analysis,preparation, review, or approval of the manuscript. The authorsare solely responsible for the design and conduct of this study,all study analyses, the drafting and editing of the paper and itsfinal contents.

Study populationThis study was drawn from 159,713 admissions with the

diagnosis of ACS (including ST-segment elevation myocardialinfarction [STEMI], non-STEMI [NSTEMI], and unstable angina),between July 2005 and December 2009, from 410 participatinghospitals across the United States. Patients were excluded if theyleft against medical advice, discontinued care, died, or weredischarged to a federal hospital, hospice, or another acute carehospital. Of the 138,216 patients discharged, 119,387 (86.4%)were receiving LLT and 14,279 (10.3%) were dischargedwithout LLT. Lipid-lowering therapy was contraindicated in4,550 (3.3%). Of patients discharged on LLT, 53,991 admissionswere also excluded because the details describing agent/dosewas missing. The data from 65,396 admissions at 344 sites werecomplete for the purposes of this analysis and formed the finalstudy population. Appendix Table 1A (online) shows thecharacteristics of patients included and excluded from thestudy population.

Lipid-lowering therapyLipid-lowering therapy was defined as therapy likely to

achieve a b50% reduction in LLT and included atorvastation 40or 80 mg, rosuvastatin 20 or 40 mg, simvastatin 80 mg, or anystatin 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 statincombination was performed to assess use and trends in intensivestatin monotherapy.Data collected included patient demographics, pertinent

medical history, symptoms on arrival, laboratory results, in-hospital treatment and procedures, discharge treatment, risk

factor counseling, and patient disposition. The lipid levelsobtained within the first 24 hours of hospitalization weremeasured at the local hospital laboratory. Yearly trends inadmission lipid values and LLT were assessed from 2005 to 2009.

Statistical analysisPatients were divided into the LLT and LLLT categories as

defined above. In addition, LLT rate were noted in varioussubgroups based on admission LDL and high-density lipoprotein(HDL). In the descriptive analysis, the mean (±SD) andpercentages were reported for continuous and categoricalvariables, respectively. For comparison of baseline characte-ristics in LLT and LLLT groups, Wilcoxon rank-sum tests wereused for continuous variables and χ2 tests for categoricalvariables. In examining the association between LDL and LLT,a multivariable logistic regression was used. The generalizedestimating equation (GEE) method with exchangeable workingcorrelation structure was used to account for within-hospitalclustering because patients at the same hospital are more likelyto have similar responses relative to patients in other hospitals(ie, within-center correlation for response). The methodproduces estimates similar to those from ordinary logisticregression, but the estimated variances of the estimates areadjusted 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 insuffi-ciency, prior MI stroke, heart failure, LLT before admission), andtype of ACS. A sensitivity analysis (28,724 subjects at 76 sites),confined to the centers with N70% statin medication dosereporting compliance, was used to exclude any selection bias inthe primary analysis. A P value of b.05 was consideredsignificant for the test of each variable. All analyses wereperformed using SAS software (version 9.2, SAS Institute, Cary,NC) by the Duke Clinical Research Institute (Durham, NC).

ResultsThe clinical characteristics of the patient study popula-

tion are shown in Table I. Admission diagnosis was MI in91.7% patients, while the remaining patients had unstableangina. There were 41.7% of patients who were receivingLLT before the index ACS admission. Admission LDL levelswere assessed in 54,892 (83.9%) of patients. Thecharacteristics of patients with and without LDL levelsassessed are shown in Appendix Table 1B (online).Patients without lipid testing during hospitalization weremore likely to have been receiving LLT before admission.At hospital discharge, there were 25,036 (38.3%) patientsreceiving LLT and 40,360 (61.7%) receiving LLLT. Patientsreceiving LLT were younger, less likely to be female, andhad higher admission LDL levels (Table I). There were30.0% of patients who received statin monotherapy,whereas 8.2% received statin/ezetimibe. The character-istics of patients receiving statin monotherapy and thosereceiving statin/ezetimibe combination are shown inAppendix Table 2 (online). Among various statins, therate of use and dosage of various statins in LLT subgroupare shown in Appendix Table 3 (online).

Table I. Baseline characteristics in intensive and less intensive LLT groups

Patientcharacteristics Overall (N = 65396) Intensive LLT (n = 25036) Less intensive LLT (n = 40360) P value

Age (y) 64.7 ± 13.9 62.6 ± 13.4 66.0 ± 14.1 b.001Female 34.3% 32.2% 35.6% b.001Race/ethnicityWhite 72.3% 71.4% 72.9% b.001Black 7.0% 7.7% 6.5% b.001Hispanic 6.4% 6.2% 6.5% .149Asian 2.8% 2.9% 2.8% .220

DiagnosisSTEMI/non-STEMI 91.7% 92.4% 91.4% b.001Unstable Angina 8.3% 7.6% 8.6% b.001

LLT taken before Admission 41.7% 44.4% 40.0% b.001Prior myocardial infarction 19.9% 21.0% 19.2% b.001Prior stroke 8.2% 7.5% 8.6% b.001Peripheral vascular disease 8.1% 8.0% 8.2% .341Hypertension 67.8% 67.5% 67.9% .319Diabetes—IDDM 9.3% 9.9% 8.9% b.001Diabetes—NIDDM 15.9% 15.9% 15.9% .993Hyperlipidemia 55.7% 58.7% 53.7% b.001Smoking (current or prior 1 y) 33.5% 35.8% 32.0% b.001β-Blockers 97.7% 98.1% 97.4% b.001ACE inhibitors 72.9% 75.5% 71.2% b.001ARBs 12.5% 12.4% 12.5% .724Aspirin 98.2% 98.6% 98.0% b.001Clopidogrel 80.8% 84.9% 78.3% b.001Warfarin 10.5% 10.2% 10.6% .187Nitrates 27.0% 27.8% 26.6% b.001Calcium channel blockers 9.0% 8.4% 9.4% b.001Aldosterone blockers 3.6% 3.8% 3.5% .066Total cholesterol (mg/dL) 170.1 ± 48.2 174.6 ± 51.0 167.1 ± 46.2 b.001LDL cholesterol (mg/dL) 103.4 ± 40.0 107.2 ± 43.0 101.0 ± 37.7 b.001HDL cholesterol (mg/dL) 38.1 ± 12.4 37.9 ± 11.9 38.3 ± 12.7 .254Triglycerides (mg/dL) 155.4 ± 124.7 161.0 ± 128.1 151.8 ± 122.3 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

HDL (mg/dL)

LDL (mg/dL)

Total(n = 45088)<70 (n = 9157)

70-100(n = 13603)

100-130(n = 11918)

130-160(n = 6672) ≥160 (n=3738)

bbbbbb40 (n = 27 762) 13.29%38.19%

18.71%36.03%

16.15%38.68%

8.76%44.14%

4.66%52.38%

61.57%39.58%

40-60 (n = 14 589) 5.70%36.95%

9.55%35.53%

8.73%37.68%

5.28%43.32%

3.10%52.58%

32.36%39.26%

≥60 (n = 2737) 1.31%33.45%

1.92%30.44%

1.56%34.33%

0.76%38.71%

0.53%44.96%

6.07%34.38%

Total (n = 45 088) 20.31%37.53%

30.17%35.51%

26.43%38.09%

14.80%43.57%

8.29%51.98%

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.

1132 Javed et alAmerican Heart Journal

December 2010

When the analysis was confined to 76 hospitals thatcollected statin dose in N70% of patients (n = 28,724), thefindings were similar (39.3% on LLT, of which 33.1%were on statin monotherapy). In comparison, the patientswithout LLT dose documentation had lower rates of

prior LLT, diabetes, hyperlipidemia (lower total choles-terol, LDL cholesterol, and triglycerides), establishedCAD, prior CABG or percutaneous coronary intervention(PCI), and acute STEMI. These patients however hadhigher prevalence of hypertension, PVD, prior MI or

Figure 1

Factors associated with LLT by multivariate GEE model.

Javed et al 1133American Heart JournalVolume 160, Number 6

cerebrovascular accident, and NSTEMI. The excludedsites also had lower rates of revascularization (PCI orCABG) and teaching hospitals.

Factors associated with LLTA number of patient characteristics were more frequent

in patients discharged with LLT (Table I). Diagnosis ofSTEMI, 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 bedischarged on LLT. There was no impact of uninsuredstatus, non–insulin-dependent diabetes mellitus, priorCABG, or HDL between the 2 groups. Table II providesthe 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 orprior MI, hyperlipidemia, LDL per 10 mg/dL rise, bodymass index (BMI) increase by 5 units, PCI with stentplacement, and male gender as independent predictors ofLLT. Patients with increasing age, chronic dialysis, and

unstable angina had a lower likelihood of receiving LLT(Figure 1). There was a marginal impact of confining theanalysis to intensive statin monotherapy and centerreporting compliance on GEE model results. In the statinmonotherapy model, diabetes mellitus, prior PCI, andprior CABG were additional independent predictorsof LLT.Temporal trends in the use of LLT were also examined.

Lipid-lowering therapy rates since the publication ofupdated National Cholesterol Education Program-ATPguidelines in 2004 increased initially from 35.5% to41.6% (2005 to 2007). However, an insignificant drop inrate of LLT was noted with a decline to 35.7% byDecember 2009. We found this to be primarily due to asignificant drop in the use of statin/ezetimibe combina-tion from 11.4% in 2007 to 3.4% in 2009 (Table III).When statin/ezetimibe combination was excluded asLLT, less than one third of ACS patients was treated withintensive statin monotherapy. Use of intensive statinmonotherapy at discharge was 28.0% in 2005 and 33.1%in 2009, without significant change during the 2007 to2009 period.

DiscussionThe present analysis shows that among hospitals

participating in GWTG-CAD, most hospitalized ACSpatients are not discharged on LLT. Even among thosewith admission LDL N130 mg/dL, 50% or less receivedLLT. 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 thistherapeutic approach was observed during 2008 to 2009.

Role of intensive LLT in ACSAlthough statins play a pivotal role in LDL reduction,

they may also exhibit a pleotropic effect by decreasingextent of myocardial ischemia, remodeling, as well aspromoting plaque stabilization and endothelial func-tion.13-15 Based on these mechanistic properties, and asdemonstrated in several clinical studies, it is now widelyaccepted that initiation of an early and intensive statintherapy in ACS is associated with reduced inpatientmortality and morbidity3,4,6,16 as well as improved long-term survival and lower rates of recurrent coronaryevents. In the MIRACL trial, LLT with atorvastatin80 mg/d (vs placebo) was started within 24 to 96hours of presentation with ACS.6 It was associated witha lower risk of symptomatic ischemia requiring emer-gent rehospitalization. This effect was independent ofbaseline LDL level, although LDL was decreased from126 to 72 mg/dL in the treatment group. The clinicalbenefit started to exhibit at 4 weeks and then persistedfor the duration of the study. The PROVE-IT TIMI 22 trialhas further demonstrated that aggressive LLT in ACS,with even lower targets LDL levels, leads to reduction in

Table III. Temporal trends of intensive LLT and intensive statin monotherapy

YearTotal

(N = 65396)Intensive LLT overall

(n = 25036)Yearlytrend P

Intensive statinmonotherapy (n = 19645)

Yearlytrend P

Ezetimibe plusstatin (n = 5391)

Yearlytrend P

2005 5283 1875 (35.49) 1422 (26.92) 453 (8.57)2006 15520 6108 (39.36) .039 4516 (29.10) .448 1592 (10.26) .0432007 18082 7523 (41.60) .138 5467 (30.23) .381 2056 (11.37) .2022008 17143 6188 (36.10) b.001 5220 (30.45) .204 968 (5.65) b.0012009 9368 3342 (35.67) .221 3020 (32.24) .734 322 (3.44) .002

1134 Javed et alAmerican Heart Journal

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revascularization and unstable angina.3,6 In PROVE-ITTIMI 22, the median LDL was decreased to 62 mg/dL on80 mg of atorvastatin in comparison to 95 mg/dL on40 mg of pravastatin. Similar to the findings in theMIRACL, the beneficial effects of high-dose statinsemerged as early as 30 days and then persisted duringthe 2 years of follow-up.Based on the available evidence, the revised Adult

Treatment Panel III guidelines has recommended anearly and LLT in patients admitted for ACS and hasincluded an optional therapeutic goal of LDL b70 mg/dLin these high-risk patients.8,9 Our analysis shows thatdespite available evidence and recommendations, in thislarge cohort of hospitalized patient with ACS, 10.3% (n =14,279) of patients with ACS were not discharged onLLT. Moreover, only 38.2% of eligible patients weredischarged on LLT. Although LDL remains the primarygoal for therapeutic intervention, the LLT prescribed atthe time of discharge may also take HDL into conside-ration. The inverse relationship of HDL and withnonfatal MI and cardiovascular-related death has beendemonstrated previously.17 The present study illustratesthat 61.6% of patients presenting with ACS have HDLlevels b40 mg/dL. To improve secondary prevention ofcardiovascular risk, it may be necessary to implementadditional lipid-modifying therapy (together with routinestatin therapy) targeting HDL N40 mg/dL in males andN50 mg/dL in females.

Lipid measurement in hospitalized patients with ACSAlthough the current guidelines recommend lipid

measurement in ACS, it is measured in less than half ofthese patients in routine clinical practice.18 This practicehas been largely based on the convention that lipid levelsare unreliable in ACS settings and usually associated withan initial decrement in total cholesterol and LDL.19

However, more recent data have shown less pronouncedchanges in lipid profile.20 In this analysis, about half ofACS patients had LDL b100 mg/dL, with LLT used inabout 36% of such patients. Although rate of LLTincreased with the rise in LDL, nearly half of patientswith LDL N160 mg/dL were still left untreated with LLT.Thus, these patients had a low probability of achievingtarget LDL in near future.

It is interesting to note that in our study, LLT was morelikely to be used in younger patients, male, smokers,overweight patients, in those with STEMI and otherwisethose more likely to undergo PCI, and those with highlipid levels. Ironically, patients with diagnosis of unstableangina, prior stroke, heart failure, and renal insufficiencywere treated with less LLLT. Moreover, there was nodifference in the type of therapy in those with priorCABG and non–insulin-dependent diabetes mellitus. Thepresent study demonstrates the underutilization of LLT inthe very high risk group, which is prone to recurrentischemic cardiovascular events.

Lipid-lowering therapy at dischargeThe available evidence suggests better long-term

compliance and higher survival rates in ACS patientsinitially discharged on statin therapy than those whowere not.7 Subsequently, the CRUSADE Quality Improve-ment Initiative also showed that the use of LLT atdischarge among select ACS patients increased from 78%in 2000 to 88% in 2004.21 The overall low rate of LLTobserved in our analyses along with recent declinesduring 2008 to 2009 are concerning and emphasize theneed for implementation of evidence-based and guide-line-recommended therapy in most patients with ACS.Although intensive statin monotherapy continued toincrease marginally, the drop-off in 2008 and 2009 inintensive LLT was essentially due to the decrease in useof ezetimibe in combination in statin therapy. However,there was no offsetting increased use of intensive statintherapy. These data represent interesting, but potentiallyunfortunate consequences of the well-publicized EN-HANCE trial controversy.22-25 In its aftermath, theplethora of discussion raised further controversy abouteven the proven benefits of statin therapy. This has had alarge impact on the contemporary practice of lipidmanagement without providing a clear alternative tothe use of ezetimibe. As a result, starting in 2008, fewerACS patients were treated with therapy that would allowthem to achieve LDL cholesterol goals recommended innational guidelines. Despite the lower use of statin/ezetimibe combination, there was little to no shift to high-dose statin therapy (at least at time of hospital discharge).These data underscore yet another impact on routine

Javed et al 1135American Heart JournalVolume 160, Number 6

clinical practice heralded by safety or lack of efficacyconcerns as raised by some recent controversies.26,27

Nevertheless, ezetimibe alone or in combination withstatin therapy has not been proven to change outcomesin ACS, so the full clinical implications of these treatmentshifts are not yet known.

LimitationsThere is a potential for selection bias in this study

because discharge LLT dosing data were not available in50% of patients. There were modest baseline differencesbetween those with and without discharge dosing oflipid therapy recorded. These factors may influence thegeneralizability of these findings. Furthermore, theGWTG-CAD database is voluntary and therefore maynot be representative of the entire US practice. Thesefindings may not reflect care at hospitals that differsubstantially from participating hospitals. Registry hos-pitals tend to be larger than nonparticipating hospitals,are more likely to be affiliated with a medical school, andare more likely to have available facilities for cardiaccatheterization, PCI, and cardiac surgery. GWTG-CADparticipating hospitals also were provided with feedbackon performance that may have also influenced the carepatterns. The hospitals participating in the GWTG-CADprogram may be more likely to prescribe LLT, such thatthe treatment gaps are even larger than what wasobserved here. Hence, the data presented here mightreflect different and possibly higher rates of LLT thanactually prescribed among patients and hospitals thatdiffer from those participating in GWTG-CAD. Althoughthe lipid levels obtained in this study were measured inthe first 24 hours of admission, they may or may not beentirely reflective of the baseline steady-state lipid levels.Furthermore, we do not have data as to whether patientswere in the fasting state. This real-world study usedresults of various commercially available lipid panelassays rather than results from a single central corelaboratory. Although this methodology may introducegreat variability to lipid testing results, this approachmakes these findings more applicable to clinicalpractice. This study only assessed LLT dosing at time ofhospital discharge. Some patients may have had subse-quent change in dosing or modification of their lipidtherapy regimen as an outpatient. As the currentguidelines do not specify a dose of statin for ACSpatients but only a target of therapy (ie, optional targetof LDL b70 mg/dL in high risk patients), many cliniciansmay believe that the titration to LLT can occur postdischarge, and this may explain the reason for thetreatment gap. The utilization of LLT at hospitaldischarge does not necessarily indicate that patientsremained adherent to their discharge regimen. Theextent of dietary and exercise counseling were notavailable in this study.

ConclusionsDuring the period of 2005 to 2009, only about one

third of patients hospitalized with ACS were dischargedon LLT. Even among patients with documented admis-sion LDL, which would require N50% reduction toachieve an optional goal of LDL b70 mg/dL, only about50% were discharged on LLT. Independent predictors ofLLT at discharge included LLT before admission, historyof hyperlipidemia or coronary artery disease, increasingBMI and lipid level, and in-hospital percutaneouscoronary intervention. In addition, the rate of adoptingLLT in ACS decreased significantly over the last 2 yearsbecause of a marked decline in the use of ezetimibe incombination with statin therapy without an offsettingincrease in intensive statin monotherapy. These findingsunderscore the importance of ongoing emphasis regard-ing implementation of current guidelines for measuringlipids and intensive statin therapy in all ACS patients.

DisclosuresDr Bhatt: research grants from Astra Zeneca, Bristol-

Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi Aventisand the Medicines Company. Dr Deedwania: consultant/advisory board of AstraZeneca and Pfizer. Dr Peterson:research funding from Bristol Myers Squibb, SanofiAventis partnership. Dr Cannon: research grants fromAccumetrics, AstraZeneca, Bristol-Myers Squibb/SanofiPartnership, Glaxo Smith Kline Intekrin Therapeutics,Novartis, Takeda, clinical advisor and equity in Auto-medics Medical Systems. Dr Hernandez: research grantfrom Johnson and Johnson, Merck, and honorarium fromAstraZeneca and Medtronic. Dr Fonarow: consultant/advisory board to Merck Schering Plough and honorariumfrom Abbott, AstraZeneca, Merck Schering Plough, andPfizer. Other authors have no disclosures.

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26. Roe MT, Chen AY, Cannon CP, et al. Temporal changes in the use ofdrug-eluting stents for patients with non–ST-segment–elevationmyocardial infarction undergoing percutaneous coronary interven-tion from 2006 to 2008: results from the Can Rapid risk stratificationof Unstable angina patients Suppress ADverse outcomes with Earlyimplementation of the ACC/AHA guidelines (CRUSADE) and AcuteCoronary Treatment and Intervention Outcomes Network–Get WithThe Guidelines (ACTION–GWTG) Registries. Circ Cardiovasc QualOutcomes 2009;2:414-20.

27. Atwater BD, Oujiri J, Wolff MR. The immediate impact of the ClinicalOutcomes Utilizing Revascularization and Aggressive Drug Evalua-tion (COURAGE) trial on the management of stable angina. ClinCardiol 2009;32:E1-3.

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Appendix

Table 1A. Patient characteristics of the study and excluded patients

Patient characteristics Overall (n = 159713) Excluded (n = 94317) Study cohort (N = 65396) P value

Age (y)

66.2 ± 14.4 67.3 ± 14.6 64.7 ± 13.9 b.001 Female 35.6% 36.5% 34.3% b.001 Race/ethnicity White 70.6% 69.4% 72.3% b.001 Black 7.4% 7.7% 7.0% b.001 Hispanic 5.6% 5.1% 6.4% b.001 Asian 3.2% 3.5% 2.8% b.001

Diagnosis

STEMI/non-STEMI 93.6% 94.9% 91.7% b.001 Unstable angina 6.4% 5.1% 8.3% b.001

LLT taken before admission

Prior myocardial infarction 20.1% 20.4% 19.9% .042 Prior stroke 8.9% 9.6% 8.2% b.001 Peripheral vascular disease 8.7% 9.2% 8.1% b.001 Hypertension 68.2% 68.6% 67.8% .003 Diabetes—IDDM 8.2% 7.1% 9.3% b.001 Diabetes—NIDDM 14.1% 12.3% 15.9% b.001 Hyperlipidemia 51.3% 47.2% 55.7% b.001 Smoking (current or prior 1 y) 31.1% 29.5% 33.5% b.001 β-Blockers 96.9% 96.3% 97.7% b.001 ACE inhibitors 70.8% 68.8% 72.9% b.001 ARBs 12.2% 12.1% 12.5% .043 Aspirin 97.4% 96.7% 98.2% b.001 Clopidogrel 75.6% 69.9% 80.8% b.001 Warfarin 11.3% 12.4% 10.5% b.001 Nitrates 17.8% 11.4% 27.0% b.001 Calcium channel blockers 6.5% 4.7% 9.0% b.001 Aldosterone blockers 3.7% 3.9% 3.6% .102 Total cholesterol (mg/dL) 168.7 ± 48.2 167.5 ± 48.1 170.1 ± 48.2 b.001 LDL cholesterol (mg/dL) 102.1 ± 40.0 101.1 ± 40.1 103.4 ± 40.0 b.001 HDL cholesterol (mg/dL) 38.5 ± 12.7 38.8 ± 13.1 38.1 ± 12.4 b.001 Triglycerides (mg/dL) 152.9 ± 122.3 150.6 ± 120.0 155.4 ± 124.7 b.001 PCI with stent 35.4% 25.1% 50.2% b.001 CABG 7.5% 6.5% 8.7% 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 = 65396) Lipids measured (n = 54892) Lipids not measured (n = 10504) P value

Age (y)

64.7 ± 13.9 64.0 ± 13.8 68.4 ± 13.9 b.001 Female 34.3% 33.6% 38.0% b.001 Race/ethnicity White 72.3% 72.4% 71.9% .290 Black 7.0% 7.1% 6.3% .002 Hispanic 6.4% 6.4% 6.2% .427 Asian 2.8% 2.4% 5.0% b.001

Diagnosis

STEMI/non-STEMI 91.7% 91.9% 91.1% .008 Unstable angina 8.3% 8.1% 8.9% .008

LLT taken before Admission

41.7% 38.7% 57.2% b.001 Prior myocardial infarction 19.9% 18.9% 24.9% b.001 Prior stroke 8.2% 7.7% 10.9% b.001 Peripheral vascular disease 8.1% 7.6% 10.7% b.001 Hypertension 67.8% 67.1% 71.4% b.001

1136.e2 Javed et alAmerican Heart Journal

December 2010

Table 1B (continued)

Patient characteristics

Overall (N = 65396) Lipids measured (n = 54892) Lipids not measured (n = 10504) P value

Diabetes—IDDM

9.3% 8.4% 13.7% b.001 Diabetes —NIDDM 15.9% 15.0% 20.8% b.001 Hyperlipidemia 55.7% 55.2% 58.2% b.001 Smoking (current or prior 1 y) 33.5% 34.9% 26.2% b.001 β-Blockers 97.7% 97.9% 96.3% b.001 ACE inhibitors 72.9% 74.0% 66.8% b.001 ARBs 12.5% 12.0% 15.1% b.001 Aspirin 98.2% 98.5% 97.0% b.001 Clopidogrel 80.8% 82.2% 73.5% b.001 Warfarin 10.5% 10.4% 11.0% .081 Nitrates 27.0% 26.8% 28.1% .008 Calcium channel blockers 9.0% 8.5% 11.8% b.001 Aldosterone blockers 3.6% 3.4% 4.7% b.001 PCI with Stent 50.2% 52.4% 38.9% b.001 CABG 8.7% 8.6% 9.0% .147 Intensive LLT 38.3% 38.9% 35.2% b.001 Intensive statin monotherapy 30.0% 30.8% 26.2% b.001 Statin/ezetimibe 8.2% 8.1% 8.9% .004

Table 2. Patient characteristics in intensive LLT groups: overall, statin monotherapy, and ezetimibe plus any statin

Patient characteristics Overall LLT (n = 25036) Statin monotherapy (n = 19645) Statin/ezetimibe (n = 5391) P value

Age (y)

62.6 ± 13.4 62.4 ± 13.5 63.6 ± 12.8 b.001 Female 32.2% 31.7% 34.0% .001 Race/ethnicity White 71.4% 69.6% 77.9% b.001 Black 7.7% 8.1% 6.3% b.001 Hispanic 6.2% 6.8% 4.2% b.001 Asian 2.9% 3.1% 2.2% b.001

Diagnosis

STEMI/non-STEMI 92.4% 93.5% 88.3% b.001 Unstable angina 7.6% 6.5% 11.7% b.001

LLT taken before admission

44.4% 41.3% 56.0% b.001 Prior myocardial infarction 21.0% 19.8% 25.2% b.001 Prior stroke 7.5% 7.3% 8.2% .038 Peripheral vascular disease 8.0% 7.4% 10.0% b.001 Hypertension 67.5% 66.3% 71.7% b.001 Diabetes—IDDM 9.9% 9.6% 11.1% .002 Diabetes—NIDDM 15.9% 15.6% 16.8% .050 Hyperlipidemia 58.7% 55.5% 70.0% b.001 Smoking (current or prior 1 y) 35.8% 37.3% 30.5% b.001 Total cholesterol (mg/dL) 174.6 ± 51.0 175.6 ± 49.9 170.8 ± 54.5 b.001 LDL cholesterol (mg/dL) 107.2 ± 43.0 108.5 ± 42.5 102.1 ± 44.6 b.001 HDL cholesterol (mg/dL) 37.9 ± 11.9 37.9 ± 11.9 38.1 ± 11.9 .085 Triglycerides (mg/dL) 161.0 ± 128.1 158.8 ± 125.0 169.4 ± 138.4 b.001

Table 3. Specific lipid-lowering agents in treatment groups

Overall

Statin Stain dose (N = 65396) Overall (%) LLT (n = 25036) LLT (%) LLLT (n = 40360) LLLT (%)

Rosuvastatin

5 mg 649 0.99 31 0.12 618 1.53 10 mg 2116 3.24 85 0.34 2031 5.03 20 mg 1156 1.77 1156 4.62 0 0.00 40 mg 417 0.64 417 1.67 0 0.00

Javed et al 1136.e3American Heart JournalVolume 160, Number 6

Table 3 (continued)

Statin

Stain dose Overall

(N = 65396)

Overall (%) LLT (n = 25036) LLT (%) LLLT (n = 40360) LLLT (%)

Atovastatin

10 mg 4122 6.30 52 0.21 4070 10.08 20 mg 5683 8.69 109 0.44 5574 13.81 40 mg 7331 11.21 7331 29.28 0 0.00 80 mg 7919 12.11 7919 31.63 0 0.00

Simvastatin

5 mg 94 0.14 2 0.01 92 0.23 10 mg 1086 1.66 24 0.10 1062 2.63 20 mg 6665 10.19 121 0.48 6544 16.21 40 mg 10887 16.65 284 1.13 10 603 26.27 80 mg 3589 5.49 3589 14.34 0 0.00

Simvastatin/ezetimibe Combination

10-10 mg 153 0.23 153 0.61 0 0.00 10-20 mg 1005 1.54 1005 4.01 0 0.00 10-40 mg 1815 2.78 1815 7.25 0 0.00 10-80 mg 603 0.92 603 2.41 0 0.00 Other 131 0.20 131 0.52 0 0.00

Statin/ezetimibe⁎

1690 2.58 1690 6.75 0 0.00

⁎ Ezetimibe and any dose of any statin in separate doses.