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Original Articles |
From the MetroHealth Campus (W.R.L.), Case Western Reserve University, Cleveland, Ohio; Berkshire Medical Center (A.G.E.), Pittsfield, Mass; Duke Clinical Research Institute (E.P., A.F.H., W.P.), Duke University Medical Center, Durham, NC; Research Triangle Institute International (K.A.L.), Waltham, Mass; Cardiovascular Division (C.P.C.), TIMI Study Group, Brigham and Womens Hospital, Boston, Mass; and the University of California (G.C.F.), Los Angeles, Calif.
Correspondence to William R. Lewis, MD, Chief, Clinical Cardiology, Heart, and Vascular Center, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Dr, Hamman 350, Cleveland, OH 44109-1998. E-mail wlewis{at}metrohealth.org
Received October 13, 2008; accepted August 28, 2009.
| Abstract |
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Methods and Results— Treatment of 237 225 patients hospitalized with CAD was evaluated in the Get With the Guidelines–CAD program from 2002 to 2007. Six quality measures were evaluated in eligible patients without contraindications: aspirin on admission and discharge, β-blockers use at discharge, angiotensin-converting enzyme inhibitor or angiotensin receptor antagonist use, lipid-lowering medication use, and tobacco cessation counseling along with other care metrics. Over time, composite adherence on these 6 measures increased from 86.5% to 97.4% (+10.9%) in men and 84.8% to 96.2% (+11.4%) in women. There was a slight difference in composite adherence by sex that remained significant over time (P<0.0001), but this was confined to patients <75 years. Composite adherence in younger patients (<75 years) increased from 87.1% to 97.7% (+10.6%) and from 83.0% to 95.1% (+12.1%) in the elderly (
75 years) over time.
Conclusions— Among hospitals participating in Get With the Guidelines–CAD, guideline adherence has improved substantially over time for both women and men and younger and older CAD patients, with only slight age and sex differences in some measures persisting.
Key Words: quality control coronary artery disease age factors sex
| Introduction |
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| WHAT IS KNOWN |
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| WHAT THE STUDY ADDS |
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| Methods |
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Guideline Adherence Measurement
Six guideline adherence measures of hospital performance were included in the analysis. Each measure was a Class I ACC/AHA guideline recommendation.1,2 These measures were selected by the GWTG-CAD program for hospital recognition and are applicable to the broadest group of patients hospitalized with CAD. All measures were defined as the percentage of eligible patients without contraindications, intolerance, or other documented medical or patient related reasons for not prescribing the intervention. These included 5 discharge measures: prescription of aspirin, β-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers for all patients with acute myocardial infarction (AMI) and left ventricular dysfunction, and prescription of lipid-lowering therapy for patients with a low-density lipoprotein cholesterol level of
100 mg/dL, and smoking cessation counseling. Additionally, 1 admission treatment measure was included: aspirin treatment within 24 hours of admission. These 6 measures were then combined into a composite performance measure (CPM) which was calculated as the number of interventions administered to eligible patients divided by the number of possible opportunities for treatment in eligible patients. Adherence to the CPM was aggregated for all patients enrolled by any hospital and was indexed according to the duration of hospital participation.
The data were analyzed in 2 separate dichotomized groups: age, less than 75 years versus greater than or equal to 75 years; and sex, men versus women. Distinct from the composite performance measure, we calculated a patient centered "all or none"9 measure reflecting the number of patients receiving all interventions for which they were eligible divided by the total number of patients expressed as a percentage. Although patients were included in the adherence analysis only if they were eligible for a given measure, patients with AMI were analyzed and reported separately along with additional care metrics. Deceased patients were included in the demographic analysis and were included in the adherence analysis if they were eligible for a given treatment. Thus, deceased patients were excluded from discharge measures.
Data Analysis
The disparity in adherence based on sex and age were evaluated over time to see whether such gaps would decrease with increasing participation in the program. Univariate adherence over time by rolling quarters comparing men versus women and younger versus older patients was performed using Cochran-Mantel-Haenszel testing for nonzero correlation, using modified Ridit scores, controlling for site. Logistic multivariable regression models were fit to compare hospital performance on older versus younger patients and women versus men over time. For the CPM, each opportunity of receiving a guideline-based measure (up to 6 measures for each patient) contributed an observation. Because younger men and women and older men and women may have other baseline differences in their characteristics, confounders were adjusted for in the regression to be able to explore the pure age/sex effects on the hospital performance. Confounders adjusted for in the model included race (white versus other), body mass index, insurance status, admission year, type of AMI diagnosis, left ventricular ejection fraction, medical histories (diabetes, heart failure, hypertension, hyperlipidemia, previous MI, peripheral vascular disease, renal insufficiency, stroke, smoking, pulmonary disease, prior percutaneous coronary intervention [PCI]/coronary artery bypass grafting [CABG]). In addition, because individual hospital characteristics may influence age/sex treatment gaps, hospital disparities were also adjusted for, including bed size, heart transplants, teaching status, region of the country, the presence of on-site CABG, and the presence of on-site PCI. In general, because of secular trends in improved adherence over time, hospitals that began participating at a later time would be expected to perform better than those started earlier. This situation was also considered in our model by adding the calendar quarter in as a covariate. Model components are listed in the online-only Data Supplement. The interaction terms were excluded from the final model with probability value >0.1. Generalized estimating equation method was applied to provide valid inference accounting for the within site correlation. Missing data were accounted for as follows: for categorical variables the most frequent category was imputed, and for continuous variables the mean from the same group was imputed. The treatment gap was expressed as the odds ratio of adherence between 2 groups to either the CPM or "all or none" measures. Improvement over time was expressed as the odds ratio for improvement, which is the ratio of the odds of adherence (CPM) at the current time compared with 1 year earlier. All statistical analyses were performed at the Duke Clinical Research Institute (DCRI) using SAS software (version 9.2, SAS Institute Inc). Because the data were deidentified, the institutional review board from MetroHealth Medical Center and DCRI granted a waiver of full institutional review board review. The authors had full access to the data and take full responsibility for its integrity. All authors have read and agreed to the manuscript as written.
| Results |
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Patient Characteristics
There were 237 225 patients enrolled in the study. Men comprised 63.1% of the patients, and 68.1% were under the age of 75. The mean age was 66.4 (±13.9) years. Most patients presented with AMI (78.6%). Six percent presented with unstable angina, and 15.4% had coronary artery disease without unstable angina or AMI. The demographic characteristics categorized by age (<75,
75 years) and sex are listed in Table 1. In general, younger patients were more likely to carry a diagnosis of hyperlipidemia and have a higher body mass index. Younger patients were also more likely to be smokers. Younger women were significantly more likely to be diabetic compared with younger men (40.5 versus 30.4%, P<0.0001). Older patients were more likely to have atrial fibrillation, hypertension, heart failure, and a prior myocardial infarction or stroke. Women were significantly older than men (70.5±13.8 versus 64.0±13.4, P<0.0001). Women were more likely to have hypertension and heart failure. Men were more likely to be smokers compared to women. Hospital length of stay was 6.3 days (IQR, 3.0 to 8.0) in older patients compared to 4.9 (IQR, 2 to 6) days in younger patients (P<0.0001). Hospital length of stay was 5.8 days (IQR, 2.0 to 7.0) in women compared with 5.2 (IQR, 2 to 6) days in men (P<0.0001). In-hospital mortality was 9.3% in older patients and 2.7% in younger patients (P<0.0001). In-hospital mortality was 6.2% in women and 4.0% in men (P<0.0001). Outcomes for younger and older male and females patients are shown in Table 1.
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75 years, there was similar composite measure conformity for older men and older women. Figure 1 shows unadjusted adherence to the CPM categorized by age and sex. Each group of patients had substantial improvement in Composite Performance Measure adherence over time (P<0.0001 for younger men, younger women, older men, and older women). Over time, composite adherence on these 6 measures increased from 86.5% to 97.4% (+10.9%) in men and 84.8% to 96.2% (+11.4%) in women. Composite adherence in younger patients (<75 years) increased from 87.1% to 97.7% (+10.6%) and from 83.0% to 95.1% (+12.1%) in the elderly (
75 years). The gap in adherence between the groups was narrowed, but slight differences remained. The percentage of older patients who were treated with each of the indicated evidence-based therapies ("all or none" performance measure) was 77.8%, compared with younger patients who received all therapies 81.2% of the time (P<0.001). Additionally, men were more likely to receive all of the evidence-based therapies ("all or none" performance measure) compared with women (81.0 versus 78.6%, P<0.0001). Both men and women aged
75 years receive similar care quality as indexed by the all or none measures. A significant unadjusted age–sex interaction (P<0.001) was found and implies different sex disparities in younger and older patients. Figure 2 shows that each group of patients had significant improvement in "all or none" measure over time (P<0.0001 for younger men, younger women, older men, and older women).
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| Discussion |
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The AHA and the ACC have published guidelines for the treatment of CAD.1,2 These guidelines recommend administration of evidence-based therapies for all eligible patients with CAD. Despite the widespread publication of these guidelines, adherence is both suboptimal and highly variable.10,11 A source of this variability remains the disparity in treatment afforded to women and the elderly. Although women and the elderly are underrepresented in clinical studies,12 these treatments have been shown to improve outcomes in both groups.13–16 As such, ACC/AHA guidelines recommend secondary prevention therapies equally to men and women and younger and older patients. Unfortunately, treatment gaps exist between these populations in many care settings.
Other studies have found that women receive evidence-based therapies less frequently compared to men. The Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines (CRUSADE) trial studied 35 875 patients with chest pain and ECG or other biomarkers for myocardial ischemia. After adjustment, women, who represented 41% of the population, were less likely to receive aspirin and β-blocker drugs on admission and aspirin, statin, and ACE inhibitor treatment on discharge.3 The differences observed between men and women in the present study are small and less than those gaps observed in CRUSADE. The absolute differences observed in CRUSADE were larger than those in this study for aspirin on discharge (2.9 versus 1.6%), βblocker on discharge (2.2 versus 1.3%), and lipid-lowering therapy on discharge (7.5 versus 5.6%).3
The clinical relevance and reason for the small sex-based treatment differences in this study are not clear. Many of the differences reported between the age and sex groups are not just small, but are unlikely to be clinically meaningful. A modest disparity was seen among younger women, a group where the diagnosis of CAD has a lower baseline probability and may be delayed until later in the hospitalization—which might be an explanation for less aggressive treatment in the first 24 hours. On the other hand, among older patients, in whom the diagnosis of CAD is more likely, treatment was similar between men and women. This suggests that initial differences in diagnostic certainty between women and men might be a contributing factor to lower guideline adherence. However, delay in treatment and difficulty in diagnosis cannot account for the differences observed for discharge measures. All of these women should have received treatment at discharge because the diagnosis was not in doubt and thus all therapies should have been applied equally. These findings are consistent with Miller and colleagues who found that despite an established diagnosis of CAD, lipid-lowering therapy was not administered equally between sexes.17 Sex bias is the basis for the awareness campaign by the AHA entitled Go Red For Women. The goal is to improve the recognition and treatment of CAD in women. There may be differences in documentation of contraindications or intolerance between patient groups which could contribute to differences in treatment rates.
Previous studies have observed that elderly patients receive appropriate treatment less frequently than younger patients. Tran et al showed that older patients with AMI were more likely to have had a prior AMI or stroke, heart failure, hypertension, or chronic obstructive lung disease.6 In their study, however, elderly patients were less likely to be prescribed aspirin on admission and discharge, βblockers on admission and discharge, and lipid-lowering therapy at discharge compared with younger patients.6 Even within the context of a quality-improvement project, the elderly receive less than optimal care. The Cooperative Cardiovascular Project, a program developed by the Centers for Medicare and Medicaid Services, included only those patients over the age of 65 years but stratified them into groups of increasing age. Older patients were prescribed aspirin and β-blocker drugs less frequently on both admission and discharge compared with younger Medicare patients.5
In the CRUSADE trial, contraindications were more frequently observed in older patients. However, in eligible patients, adjusted prescription of aspirin and βblocker drugs on admission and lipid lowering therapy on discharge were lower in older patients.4 Again, compared to CRUSADE, the differences observed between older and younger patients is less in the current study: absolute differences in aspirin on discharge (3.0 versus 2.1%) and βblocker on discharge (3.1 versus 1.6%).4 Yarzebski et al found that physicians were less likely to prescribe lipid agents to elderly patients. Factors that influenced the decision to prescribe these agents included the cost of medication, the feeling that these drugs are not as effective as other medications, and the attitude that dietary therapy is an alternative treatment.18 Thus, a physician may limit the aggressiveness of their treatment based on a feeling that an elderly patient will have less clinical benefit and greater costs. Additionally, medical treatment lags behind clinical trial evidence. Antman et al demonstrated that even expert recommendations for particular therapies may lag years behind conclusive clinical trials.19 Although there are several studies demonstrating the effects of lipid lowering therapy in younger patients, trials specifically involving the elderly have only recently been published.16 This could explain the slower incorporation of these treatments into standard therapy for the elderly.
Our findings are consistent with those of Jani et al, who found that application of the Guidelines Applied In Practice program improved adherence to guidelines in women and men.20 They did not control for both age and sex terms in their model, which was performed in the present study.
This is the largest study to date which demonstrates improvement in guideline adherence regardless of sex or age over time using a quality-improvement program. The AHA GWTG-CAD Program uses a collaborative model for quality-improvement with workshops and multiple reinforcing strategies between face to face sessions to improve cardiovascular care. In addition, the Patient Management Tool facilitates concurrent review and management. LaBresh et al has shown that participation in this program is associated with improved adherence to guidelines over a 1-year period.7 In addition, guideline adherence in GWTG-CAD hospitals is significantly better than non-GWTG hospitals in the Hospital Compare database.21 The GWTG program was not designed to address differences in clinical presentation between men and women and younger and older patients, and thus therapies should be applied indiscriminately.
The GWTG program with quality-improvement processes and Patient Management Tool promotes standardized care and should limit age and sex treatment disparities. The cause of small persistent differences in care is not clear. Diagnostic uncertainty is an unlikely cause, as patients would not have been entered into the database without a confirmed diagnosis. Intolerance or contraindication to medications should not be relevant as patients would not have been eligible for treatments if they were intolerant. Further study is necessary to determine the cause of these remaining treatment disparities and develop techniques for closing these treatment gaps. As demonstrated in Table 2, treatment gaps for some individual performance measures were narrow. However, for some measures, the treatment gaps were large representing significant opportunities for improvement. The largest gaps in sex and age were observed in lipid treatment. Additionally, treatment gaps between younger and older patients included the administration of ACE inhibitors or ARB for left ventricular dysfunction and tobacco cessation counseling. Focusing further education on these individual measures represents the best opportunity to narrow treatment gaps in guideline adherence.
Limitations
This study was not a randomized clinical trial, and the improvements in performance measures may have been influenced by factors other than GWTG-CAD participation such as secular trends. Data were collected by medical chart review and depend on the accuracy and completeness of documentation. As such, a proportion of patients reported to be eligible for treatment who did not receive recommended treatments may have had contraindications or intolerance to specific interventions that were present but not documented. Participation in GWTG is voluntary and may select for higher performing hospitals. It is possible that, as such, higher adherence may have been observed; however, this is unlikely to have affected the differences between age and sex. Despite multivariable adjustment we cannot exclude that residual measured and unmeasured confounding may account for these observations. Each patient contributes several measures to the CPM. The generalized estimating equation model may not fully account for the within patient correlation. The term "disparity" in this study included patient and hospital factors and thus differs with the Institute of Medicine definition. As GWTG does not collect data on postdischarge outcomes, the full implications of these improvements in process measure treatment rates for women and older patients over time, but without elimination of the treatment gaps, could not be directly explored.
Conclusions
Improvement in adherence to guidelines, including pharmacological and nonpharmacologic management, for the treatment of CAD was demonstrated in younger and older women as well as younger and older men over a 5-year period among GWTG-CAD participating hospitals. These patterns differ from prior studies showing reductions in evidence-based therapy in relation to age and sex among CAD patients, and thereby suggest that clinicians may have become more adherent with guideline-based therapeutic recommendations for their older and women patients, particularly in the framework of a guideline-based performance improvement program. Small treatment differences observed between men and women less than age 75 years and between younger and older patients irrespective of sex were not eliminated, however, over the study period. Further study to determine whether these small remaining treatment differences are clinically relevant is warranted.
| Acknowledgments |
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This study was funded by the American Heart Association.
Disclosures
Dr Lewis has received speaker honoraria from Reliant Pharmaceuticals and has served as a consultant for Medtronic. Dr Peterson has received research funding from Schering Plough/Merck and BMS/Sanofi. Dr Hernandez has received research funding and/or honoraria from Johnson & Johnson/Scios, GlaxoSmithKline, Medtronic, Novartis, and AstraZeneca. Dr LaBresh is an employee of Research Triangle Institute International. Dr Cannon has received research funding from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, Merck, Merck/Schering Plough Partnership and has ownership interest in Automedics Medical Systems. Dr Fonarow has received research funding and honoraria from and served as a consultant for Medtronic, GlaxoSmithKline, and Novartis; has received other research support from Pfizer; and has served as a consultant for and received honoraria from BMS/Sanofi, Merck, and Schering.
| Footnotes |
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3. Blomkalns AL, Chen AY, Hochman JS, Peterson ED, Trynosky K, Diercks DB, Brogan GX Jr, Boden WE, Roe MT, Ohman EM, Gibler WB, Newby LK; CRUSADE Investigators. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol. 2005; 45: 832–837.
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