Author + information
- Received June 12, 2017
- Revision received October 30, 2017
- Accepted December 5, 2017
- Published online February 19, 2018.
- Carolina Malta Hansen, MD, PhDa,∗ (, )
- Tracy Y. Wang, MD, MHS, MSca,
- Anita Y. Chen, MSa,
- Karen Chiswell, PhDa,
- Deepak L. Bhatt, MD, MPHb,
- Jonathan R. Enriquez, MDc,
- Timothy Henry, MDd and
- Matthew T. Roe, MD, MHSa
- aDuke Clinical Research Institute, Durham, North Carolina
- bBrigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts
- cUniversity of Missouri-Kansas City, Kansas City, Missouri
- dCedars-Sinai Heart Institute, Los Angeles, California
- ↵∗Address for correspondence:
Dr. Carolina Malta Hansen, Duke Clinical Research Institute, 2400 Pratt Street, Durham, North Carolina 27705.
Objectives The study sought to characterize patient- and hospital-level variation in early angiography use among non–ST-segment elevation myocardial infarction (NSTEMI) patients.
Background Contemporary implementation of guideline recommendations for early angiography use in NSTEMI patients in the United States have not been described.
Methods The study analyzed NSTEMI patients included in ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry (2012 to 2014) who underwent in-hospital angiography. Timing of angiography was categorized as early (≤24 h) vs. delayed (>24 h). The study evaluated factors associated with early angiography, hospital-level variation in early angiography use, and the relationship with quality-of-care measures.
Results A total of 79,760 of 138,688 (57.5%) patients underwent early angiography. Factors most strongly associated with delayed angiography included weekend or holiday presentation, lower initial troponin ratio values, higher initial creatinine values, heart failure on presentation, and older age. Median hospital-level use of early angiography was 58.5% with wide variation across hospitals (21.7% to 100.0%). Patient characteristics did not differ substantially across hospitals grouped by tertiles of early angiography use (low, middle, and high). Hospitals in the highest tertile tended to more commonly use guideline-recommended medications and had higher defect-free care quality scores.
Conclusions In contemporary U.S. practice, high-risk clinical characteristics were associated with lower use of early angiography in NSTEMI patients; hospital-level use of early angiography varied widely despite few differences in case mix. Hospitals that most commonly utilized early angiography also had higher quality-of-care metrics, highlighting the need for improved NSTEMI guideline adherence.
The prevalence of non–ST-segment elevation myocardial infarction (NSTEMI) has increased markedly over the past several decades and now accounts for approximately two-thirds of acute coronary syndrome (ACS) hospital admissions (1–3). During the past 20 years, several randomized clinical trials have demonstrated the benefits of early invasive management (i.e., early coronary angiography within 48 to 72 h with provisional use of revascularization) versus conservative management (i.e., medical stabilization and triage to angiography only for refractory ischemia) for NSTEMI (4–6).
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) quality improvement initiative studied high-risk unstable angina/NSTEMI patients from 2000 to 2002. CRUSADE found that less than one-half of these patients received angiography within 48 h, as recommended by practice guidelines at that time (1,7,8). Although angiography use <48 h has increased in the United States in the post-CRUSADE era, underutilization of early angiography has been observed among patients at elevated risk of clinical events (e.g., those with advanced age, chronic kidney disease, and diabetes mellitus) and among certain demographic groups (e.g., black race and female sex) (7,9–11).
Concurrently, the recommended timing of early angiography for NSTEMI has evolved based upon the results of several contemporary clinical trials that have evaluated shorter time intervals to angiography, ranging from 2 to 48 h (4–6,12–17). Meanwhile (18,19), the 2002 U.S. practice guidelines first endorsed early angiography (defined as angiography ≤48 h of hospital admission) as a Class IA recommendation for NSTEMI patients who were unstable or had an elevated risk for clinical events (8). Since then, practice guideline updates have progressively shortened the recommended angiography time interval in NSTEMI patients with high-risk characteristics to within 24 h of presentation (18,19). Although extensive efforts have been made to shorten the time to angiography and reperfusion with primary percutaneous coronary intervention (PCI) for patients with ST-segment elevation myocardial infarction (STEMI), the contemporary timing of angiography among NSTEMI patients in the United States has not been well-characterized, including the time period following the release of the updated 2012 American College of Cardiology Foundation/American Heart Association (AHA) Focused Update of the Unstable Angina/NSTEMI Guideline (20–25).
In order to better understand contemporary patterns of angiography, we utilized the National Cardiovascular Data Registry ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry database to characterize contemporary patterns of early angiography ≤24 h of presentation for NSTEMI patients, patient- and hospital-level factors associated with early angiography, and hospital-level variation in the use of early angiography.
The ACTION registry (26) is a voluntary quality improvement registry in the United States that includes consecutive patients admitted to participating hospitals with STEMI or NSTEMI. Definitions for the data elements of the registry are available at the National Cardiovascular Data Registry website (https://www.ncdr.com/webncdr/action/home/datacollection). This registry is part of a quality improvement initiative sponsored by the American College of Cardiology (ACC) and AHA. The ACTION registry includes data abstraction training, data quality thresholds for inclusion, site data quality feedback reports, independent auditing, and data validation. Auditing of data has demonstrated chart review agreement of >93% of collected variables (27). At participating sites, registry participation was approved by an Institutional Review Board.
The target population for this study included patients who presented directly to PCI-capable hospitals participating in the ACTION registry, and who received invasive coronary angiography. We included 245,966 patients with NSTEMI between January 1, 2012, and December 31, 2014 from 697 ACTION registry hospitals. Patients were sequentially excluded if they were from participating hospitals that did not have PCI capabilities (n = 3,504; 42 sites), initially presented to outside hospitals and were subsequently transferred into an ACTION registry participating hospital (n = 68,115), had a documented contraindication for angiography (n = 27,719), did not undergo angiography (n = 7,682), or had missing hospital arrival to angiography times (n = 258). After these exclusions, the final study population comprised 138,688 NSTEMI patients from 661 hospitals.
Based on the 2012 AHA/ACC Guideline for the Management of Patients with NSTE ACS, the timing of angiography for patients included in this analysis was categorized as: 1) early angiography (hospital arrival to angiography ≤24 h, including those who received urgent angiography [i.e., <2 h of presentation]); or 2) delayed angiography (hospital arrival to angiography >24 h) (1). Weekday arrival was defined as weekdays (Monday 8 am through Friday 5 pm). Weekend or holiday arrival was defined as hospital arrival from Friday after 5 pm until Monday 8 am for weekends and for holidays, including New Year’s Day (December 31 to January 1), Christmas Day (December 24 to 25), Memorial Day (relevant calendar dates for 2012 to 2014), Independence Day (July 4), Labor Day (relevant calendar dates for 2012 to 2014), and Thanksgiving Day (Wednesday 5 pm through Monday 8 am following the annual Thanksgiving holiday). The defect-free care score is a composite quality performance measure utilized for quality reporting to ACTION registry hospitals and is based on ACC/AHA guideline recommendations for the treatment of NSTEMI patients. The defect-free score includes acute (within 24 h of hospital arrival) aspirin, evaluation of left ventricular systolic function, aspirin, beta-blocker, statin, and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for left ventricular systolic dysfunction prescribed at discharge; adult smoking cessation advice counseling; and cardiac rehabilitation patient referral from an inpatient setting. The overall hospital-level defect-free care score was calculated for each hospital as the percentage of NSTEMI patients who received all of the recommended treatments, interventions, and diagnostic evaluations within the score after accounting for documented contraindications for each component of the score. If a patient failed to receive even a single therapy for which she or he was eligible, then that patient failed to meet the “defect-free” criteria and was removed from the numerator.
To explore the relationship between the baseline variables (i.e., patient baseline characteristics, treatment patterns, and hospital characteristics) and patient-level use of angiography (≤24 h of presentation vs. >24 h), chi-square and Wilcoxon rank sum tests were used to compare categorical and continuous variables, respectively. Categorical variables were reported as percentages (frequencies), and continuous variables were reported as medians with 25th and 75th percentiles.
A supplementary analysis was also performed to characterize patients who underwent angiography ≤72 h versus >72 h to comprehensively describe patients with very delayed angiography. To investigate factors associated with early angiography ≤24 h, we used a logistic generalized estimating equations regression with an exchangeable working correlation matrix to account for within-hospital clustering of outcome to model the probability of early versus delayed angiography (28). Although this working correlation structure assumes that hospitals are independent after adjusting for covariates, empirical SE estimates were used for inference, which provides robustness against possible misspecification of the correlation structure. Potential covariates for the model were identified based on our collective clinical judgment and included demographics, signs and symptoms at presentation, medical history, laboratory results, home medications, insurance status, weekend or holiday presentation, and selected hospital characteristics (Online Appendix). Furthermore, linearity for continuous covariates with respect to log odds of early angiography was checked. Cutoff points were considered where the relationship between the covariate and early angiography became flat or nonlinear, and finalized once determined to be clinically appropriate. Adjusted odds ratios, 95% confidence intervals, and chi-square statistics were reported for the covariates in the model. Last, the percentage of missingness for each covariate was approximately 1% to 2%; therefore, missing values in continuous covariates were imputed to the sex-specific median of the nonmissing values, and missing values in categorical covariates were imputed to the most frequent group.
To further explore patterns of early angiography use, we assessed hospital-level variation. For this particular analysis, patients admitted to hospitals with ≤40 NSTEMI patients during the study period were excluded (n = 2,014; 112 sites) to focus only on hospitals with adequate NSTEMI patient volume. Hospitals were sorted by the proportion of patients who received early angiography, and divided into 3 groups: low, middle, and high tertiles. Hospitals in the low-tertile group had the lowest proportion of patients who received early angiography. For this analysis, patient baseline characteristics, treatment patterns, and hospital characteristics were stratified by tertiles of hospital-specific utilization of early angiography. Chi-square and Kruskal-Wallis tests were used to compare categorical and continuous variables, respectively. A sensitivity analysis was performed, and was restricted to hospitals that submitted data for 12 consecutive quarters.
A p value of <0.05 was considered significant for all analyses. All statistical analyses were performed using SAS version 9.4 software (SAS Institute, Cary, North Carolina).
We analyzed 138,688 NSTEMI patients from 661 hospitals undergoing in-hospital angiography at the presenting hospital between January 1, 2012, and December 31, 2014. Overall, 57.5% (79,760 of 138,688) of these patients underwent early angiography (≤24 h). Compared with patients for whom angiography was delayed beyond 24 h, patients who underwent early angiography were more commonly younger or had higher initial troponin ratio values (Table 1). Figure 1 shows the percentage of early angiography among patient subgroups. Early angiography was more common among men versus women (60.0% vs. 53.1%), whites versus other (59.2% vs. 51.5%), those who had cardiogenic shock versus those without shock (70.6% vs. 57.3%), those with cardiac arrest on presentation versus no arrest (67.6% vs. 57.4%), and those who were admitted during weekday versus weekend or holiday (64.0% vs. 44.7%). Conversely, early angiography was less common among patients who had prior myocardial infarction versus no myocardial infarction (52.3% vs. 59.6%), those with prior PCI versus no PCI (54.2% vs. 59.0%), and those with prior coronary artery bypass grafting versus no coronary artery bypass grafting (49.7% vs. 59.1%). Patients who underwent early angiography were more likely to receive acute and discharge P2Y12 receptor inhibitors than were patients who underwent delayed angiography (Online Table 1).
Factors associated with early angiography
After adjusting for patient and presentation characteristics and hospital characteristics, patients with weekend or holiday presentation, higher initial serum creatinine values (per 1 mg/dl increase for values ≥1 mg/dl), heart failure on presentation, and those of older age were less likely to undergo early angiography, whereas patients with higher initial troponin ratios were more likely to undergo early angiography (Table 2).
Hospital-level pattern of invasive strategies
For analysis of hospital-level variation in the use of early angiography, a total of 136,674 NSTEMI patients from 549 hospitals with >40 eligible NSTEMI patients during the study period were included. Median hospital-level use of early angiography was 58.5% (25th to 75th percentiles: 49.5% to 68.1%) with a wide range across hospitals (minimum of 21.7% to maximum of 100%) (Figure 2A). A sensitivity analysis that included hospitals submitting data for 12 consecutive quarters from 2012 to 2014 showed a similar pattern of variation with median hospital-level use of early angiography at 58.9% (25th to 75th percentiles: 50.7% to 68.2%) (Figure 2B).
Demographic and clinical characteristics summarized according to hospital tertiles of early angiography use are shown in Table 3. The proportion of patients presenting during a weekend or holiday was similar across tertiles. Patients in the highest hospital-level tertile of early angiography were more likely to be white, be male, and have health maintenance organization or private insurance compared with patients in the lowest tertile. Compared with patients in the lowest tertile, patients in the highest tertile were more likely to have cardiac arrest, cardiogenic shock, or new (or presumed new) ST-segment depression, and were less likely to have a Global Registry of Acute Coronary Events in-hospital mortality risk score >140 or heart failure on presentation.
Table 4 shows hospital characteristics according to tertiles of early angiography use. Hospitals in the highest tertile were the least likely to be academic centers and had lower annual volumes of NSTEMI patients. A higher proportion of hospitals in the Midwestern or Western regions of the United States were in the highest tertile of early angiography. Hospital-level defect-free scores increased across hospital tertiles with the highest values observed in the upper hospital tertile of early angiography use.
Characteristics of patients with longer delays to angiography
Online Table 2 shows characteristics of patients who underwent angiography ≤72 h versus >72 h of hospital presentation. A total of 8.1% (n = 11,286) patients underwent angiography >72 h after hospital admission; these patients had substantial differences in clinical characteristics compared with those who underwent angiography ≤72 h of presentation.
Among NSTEMI patients undergoing in-hospital angiography in contemporary U.S. practice, we found that only 58% underwent early angiography (≤24 h) and that high-risk clinical characteristics recommended by practice guidelines for triage to early angiography were associated with lower use of early angiography. There was wide variation in the hospital-level use of early angiography despite few differences in case mix across hospitals. Finally, there was an association between higher quality-of-care metrics among hospitals with higher utilization of early angiography.
By delineating factors associated with the use of early angiography, our findings highlight gaps in the implementation of the 2012 AHA/ACC Guideline for the Management of Patients with NSTE ACS that was released at the beginning of our analysis time period (18). Although certain high-risk features such as cardiac arrest and cardiogenic shock on presentation were associated with greater utilization of early angiography (as recommended by the 2012 American College of Cardiology Foundation/AHA Focused Update of the Unstable Angina/NSTEMI Guideline), other high-risk clinical characteristics such as older age, chronic kidney disease, and heart failure on presentation (risk factors in the Global Registry of Acute Coronary Events risk score) were inversely associated with early angiography (1,18). Physicians may expect higher complication rates with early angiography or PCI in this population and, therefore, may choose a more conservative approach. Importantly, weekend or holiday presentation, which is a factor previously associated with lower use of invasive cardiac procedures and higher mortality among patients with myocardial infarction, was also associated with a much lower likelihood of early angiography (29,30). These findings were observed despite the fact that one-third of patients consistently presented during weekends or holidays across the hospital tertiles of early angiography, thereby indicating that hospitals in the highest tertile may be better equipped to handle the logistical aspects of performing early angiography for NSTEMI patients during nonworking hours. Nevertheless, several factors that may have influenced angiography timing (e.g., patient preferences, contrast allergies that required medication pretreatment, and respiratory issues that required treatment before angiography could be safely performed) were not measured with the data collection process and, therefore, cannot be ascertained. Finally, although underutilization of invasive cardiac procedures has previously been reported among black patients, women, and those without health maintenance organization or private insurance, our results show that similar disparities persist in the use of early angiography for these patients (7,9–11,31). As a result, further analyses of factors that directly influence physician decision making in referring NSTEMI patients for early angiography are needed to evaluate the complex interplay of factors that contribute to the use (and nonuse) of early angiography.
We observed wide hospital-level variation in the use of early angiography, ranging from 22% to 100% of all NSTEMI patients who underwent in-hospital angiography; this finding was unique to our analysis, and was observed despite few differences in clinical characteristics across hospital tertiles of early angiography. Hospitals in the highest tertile of early angiography use were less likely to be academic, had lower annual NSTEMI volumes, and had fewer hospital beds, but had higher hospital-level defect-free quality scores. Such findings may reflect logistical challenges facing larger hospitals (that may be more likely to be within academic health systems) for performing early angiography for NSTEMI patients. Also, these findings highlight potential challenges surrounding the implementation of the more recent 2014 AHA/ACC Guideline for the Management of Patients with NSTE ACS revisions (1). Importantly, these updated guidelines designate hemodynamically unstable patients who should receive very early (vs. early) angiography (<2 h of presentation vs. ≤24 h), so these recommendations may place an even greater logistical demand on health care systems (18). Nonetheless, our findings highlight the challenges of meeting a less stringent time metric for early angiography for NSTEMI patients (≤24 h vs. >24 h), so the impact of the new 2014 guideline recommendations for the use of very early angiography will require further study as more data accrues over time.
Collectively, our results suggest that time-sensitive treatment algorithms similar to those used to accomplish timely reperfusion with primary PCI for STEMI are needed to promote the use of timely angiography within 24 h of hospital presentation for NSTEMI patients (21,32). Although the use of early angiography for NSTEMI patients is not yet recognized as a key quality metric for NSTEMI, incorporating the use of early angiography into the NSTEMI performance measures may have the downstream impact of improving adherence to all practice guideline recommendations for NSTEMI (25,33).
First, to fairly study patterns of early angiography use, we excluded patients who were transferred into ACTION registry hospitals, those who were included from ACTION registry participating hospitals without PCI capabilities, and those who had a documented contraindication for angiography. As a result, the population that we studied was highly selective and only included patients who actually underwent angiography at hospitals with revascularization capabilities; consequently, further studies are needed to evaluate patterns and timing of angiography use for NSTEMI patients who initially present to hospitals without revascularization capabilities. Second, a survival bias was present because we excluded patients who died soon after hospital arrival (before angiography could be performed). Third, our study was not designed to assess outcomes; therefore, we did not include outcomes data (e.g., survival or reinfarction). Because the association between adherence to guideline practices and improved outcomes has previously been shown, we have assumed that adherence to guideline practices is associated with improved outcomes (7,33). Finally, our results demonstrated unequal regional (geographic) participation in ACTION registry, which might have resulted from the voluntary nature of ACTION registry hospital involvement, but nonetheless might have biased the analyses of nationwide hospital-level patterns of early angiography use.
Among NSTEMI patients undergoing angiography in contemporary U.S. practice, only 58% underwent early angiography within 24 h of presentation and wide variation in early angiography use was observed across hospitals. Composite quality-of-care measures were higher among hospitals that more frequently utilized early angiography, which suggests that increased use of early angiography for appropriate NSTEMI patients should be an aspirational goal for quality improvement interventions at the local, regional, and national levels. Further analyses of factors that directly influence physician decision making in referring NSTEMI patients for early angiography are needed to evaluate the complex interplay of factors that contribute to the use (and nonuse) of early angiography.
WHAT IS KNOWN? Practice guideline updates have progressively shortened the recommended angiography time interval in NSTEMI patients with high-risk characteristics to within 24 h of presentation.
WHAT IS NEW? Our study found that high-risk clinical characteristics were inversely associated with the use of early angiography for patients with NSTEMI. Furthermore, hospital-level use of early angiography varied widely despite few differences in case-mix across hospitals. Hospitals that most commonly utilized early angiography also had higher quality of care metrics; therefore, our findings highlight opportunities to improve NSTEMI guideline adherence.
WHAT IS NEXT? Treatment algorithms similar to those used in STEMI care may be necessary to ensure that NSTEMI patients receive timely angiography within at least 24 h of hospital presentation. Finally, recognizing the use of early angiography, along with other performance measures, may promote greater adherence to all NSTEMI practice guideline recommendations.
The authors would like to thank Erin Campbell, MS, for her editorial contributions to this manuscript. Ms. Campbell did not receive compensation for her assistance, apart from her employment at the institution where this study was conducted.
This project was funded by the American College of Cardiology’s National Cardiovascular Data Registry. The views expressed in this manuscript represent those of the author(s), and do not necessarily represent the official views of the National Cardiovascular Data Registry or its associated professional societies identified at CVQuality.ACC.org/NCDR. The ACTION registry is an initiative of the American College of Cardiology and the American Heart Association, with partnering support from Society of Cardiovascular Patient Care, and the American College of Emergency Physicians. Dr. Malta Hansen has received research grants from TrygFonden, Helsefonden, and the Laerdal Foundation. Dr. Wang has received research funding from AstraZeneca, Gilead, Eli Lilly, The Medicines Company, Pfizer, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Regeneron, and Canyon Pharmaceuticals; participated in educational activities or lectures (generating money for Duke) for AstraZeneca (modest); and served as a consultant for Medco (modest) and American College of Cardiology (significant). Dr. Bhatt has served on the advisory board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the Board of Directors of the Boston VA Research Institute and Society of Cardiovascular Patient Care; has served as the chair of American Heart Association Quality Oversight Committee; has served on the data monitoring committees of the Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), J Am Coll Cardiol (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); has served as the Deputy Editor for Clinical Cardiology; has served as the chair of the NCDR-ACTION Registry Steering Committee and VA CART Research and Publications Committee; has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Eli Lilly, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald Heart Disease); has served as a site co-investigator for Biotronik, Boston Scientific, and St. Jude Medical (now Abbott); has served as a trustee of American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Roe has received research funding from Eli Lilly, Sanofi, Daiichi Sankyo, Janssen Pharmaceuticals, Ferring Pharmaceuticals, Myokardia, AstraZeneca, the American College of Cardiology, the American Heart Association, the Familial Hypercholesterolemia Foundation; and has served as a consultant for or received honoraria from PriMed, AstraZeneca, Boehringer Ingelheim, Merck, Actelion, Amgen, Myokardia, Eli Lilly, Novartis, Daiichi Sankyo, Quest Diagnostics, and Elsevier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- American College of Cardiology
- acute coronary syndrome(s)
- American Heart Association
- non–ST-segment elevation myocardial infarction
- percutaneous coronary intervention
- ST-segment elevation myocardial infarction
- Received June 12, 2017.
- Revision received October 30, 2017.
- Accepted December 5, 2017.
- 2018 American College of Cardiology Foundation
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