Determinants of use and outcomes of invasive coronary procedures in acute coronary syndromes: results from ENACT
Philippe Gabriel Stega,*,
Bernard Iunga,
Laurent J Feldmana,
Aldo P Maggionib,
Ulrich Keilc,
Jaap Deckersd,
Dennis Cokkinose and
Keith A.A Foxf for the ENACT investigators
a Hôpital Bichat, 46 rue Henri Huchard, 75877 Paris Cedex 18, France
b ANMCO Research Center, Florence, Italy
c Institut für Epidemiologie und Sozialmedizin, Universität Münster, D-48149 Münster, Germany
d Cardialysis BV, Rotterdam, The Netherlands
e Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece
f Cardiovascular Research, Department of Medical and Radiological Sciences, The University of Edinburgh, Edinburgh, UK
* Corresponding author. Tel.: +33-1-4025-8668; fax: +33-1-4025-8865
E-mail address: gabriel.steg{at}bch.ap-hop-paris.fr
Received 18 October 2002;
accepted 23 October 2002
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Abstract
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Aims To explore the variations in the use of invasive coronary procedures after acute coronary syndromes.
Methods and results In the ENACT registry, use of invasive procedures was analyzed as a function of hospital type, country and patient characteristics among 2768 patients with acute coronary syndromes (731 with ST-segment elevation myocardial infarction (STEMI) within 12h of symptom onset, and 2037 with other acute coronary syndromes). Percutaneous coronary intervention (PCI) was more likely to be performed in teaching than in community hospitals, and in hospitals with, rather than without, catheterization facilities. There were marked country-to-country variations in the use of PCI during the index hospital stay, ranging from 8 to 67% after STEMI
and from 9 to 44% after other acute coronary syndromes
. The main independent predictors of the performance of PCI were the country rate of use of PCI and the hospital availability of PCI. For patients with other acute coronary syndromes, the risk of adverse events, assessed by the simplified TIMI-risk score, was not associated with PCI. Logistic regression analysis showed that lack of PCI was an independent predictor of in-hospital mortality (odds ratio (OR): 3.75,
) after other acute coronary syndromes, but not after STEMI.
Conclusions The use of PCI after acute coronary syndromes appears related more to local practice and hospital characteristics than to patients' characteristics or risk.
Key Words: Acute coronary syndromes Coronary angiography Percutaneous coronary intervention
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1. Introduction
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There is considerable variation in the use of angiography and percutaneous intervention amongpatients with acute coronary syndromes (ACS).15 This variation may be related not only to theheterogeneity of this condition, but also to hospital characteristics,6 as well as local or national variations.7,8 At present, there is little PanEuropean information available on the use of proceduresin ACS patients. The ENACT registry provides an opportunity to examine the use of procedures asa function of the type of patient, hospital and country.
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2. Methods
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The ENACT registry collected prospectively PanEuropean information on the relative frequency, diagnosis and management of patients admitted with suspected ACS. Data were collected from April to June 1999 for 3092 patients from 390 sites in 29 European countries. In this cohort, 324 patients were discharged with a final diagnosis of non-cardiac disease and were excluded from the analysis. Therefore the present study addresses 2768 patients, who were divided into 731 patientswith ST-segment elevation myocardial infarction (STEMI) within 12h of symptom onset, and 2037 patients with other ACS.
The methods and main results of the ENACT survey have been previously published.1,9 Briefly, participating hospitals were asked to collect information on the first 10 consecutive patients admitted to their coronary care units with symptoms of unstable angina or acute myocardial infarction (MI), during a 7-day period between April and June 1999. From the patient medical record, baseline clinical, ECG and biochemical characteristics of the patients, prior medical history, final diagnosis, management procedures, discharge therapy, as well as the duration of ICU/CCU and total hospital stay were collected. Information was also collected on each participating hospital regarding their management strategies and the facilities available for coronary intervention or cardiac surgery.
The data were examined in three different views: on the basis of hospital type (in whichhospitals were stratified on the basis of availability of on-site angiography, and of participation in a teaching program); on the basis of country ofenrollment; and on the basis of the procedures (coronary angiography and angioplasty) followed during the index hospital stay for each individual patient. A hospital with a catheterization laboratory was defined as one where the investigator undertook angiography on site. For patients withnon-STEMI or unstable angina only, risk stratification was done using the simplified risk stratification scheme developed by the TIMI group, using age, ST deviation on the admission electrocardiogram and the detection of elevated levels of serum cardiac markers.10 According to this scheme, patientswere stratified into three groups: low (score of 0/1), intermediate (score of 2), or high (score of 3) risk.
2.1. Statistical methods
Quantitative variables were expressed as mean±standard deviation. Comparisons between groups and univariate analysis of the predictive factors of in-hospital percutaneous coronary intervention (PCI) and in-hospital mortality used one-way analysis of variance for quantitative variables and chi-square test for qualitative variables. Length of stay was censored for in-hospital death, i.e. it was taken into account only for patients who were discharged alive.
Univariate analysis included 24 variables: three variables related to the type of hospital (teaching vs. community, presence of catheterizationlaboratory and of on-site PCI), 10 variables related to the patient including the simplified TIMI score (shown in Table 1), seven variables related to the drugs used during hospitalization (use of aspirin, heparin, beta-blockers, calcium-channel blockers, nitrates, ACE inhibitors), the performance of coronary angiography, PCI and bypass grafting during hospitalization, and the type of country. Countries were classified into three groups according to the use of PCI in centers participating in the present study:
- High use (
40%): Austria, France, Germany, Poland;
- Intermediate use (20 to 40%): Belgium, Croatia, Cyprus, Czech Republic, Egypt, Hungary, Ireland, Israel, Italy, Lithuania, Netherlands, Portugal, Spain, Sweden ,Turkey; and
- Low use (<20%): Bulgaria, Denmark, Finland, Greece, Latvia, Norway, Romania, Slowak Republic, Switzerland, United Kingdom.
The type of country and the simplified TIMI score were recorded using dummy variables.
Variables with
were entered in a logistic regression and selected by a backward procedure with a significance level of
, except for the simplified risk stratification TIMI score, which was systematically maintained in the models predicting the use of PCI. Adjusted odds-ratios were derived from the coefficients of the final multivariate logistic model. The fit of the models was assessed by comparing the predicted and observed numbers of good and inadequate immediate results for different classes of predicted probability of good results, according to the method described by Hosmer and Lemeshow. All analyses were performed with SAS statistical software.
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3. Results
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3.1. Analysis by hospital type
The baseline characteristics of patients, stratified according to the type of hospital, are summarized in Table 1. Although there were some statistically significant differences, the main baseline characteristics overall appeared similar between thepatients admitted in teaching as opposed to the community hospitals, and in the patients admitted to hospitals with catheterization laboratories as opposed to admitted in without catheterization laboratories. Patients with other ACS, admitted to teaching hospitals, had very similar risk scoresregardless of the type of hospital they wereadmitted in.
For both, patients with STEMI as well as those with other ACS, there were far more interventional procedures performed during the index hospital stay among patients admitted in teaching hospitals rather than in community hospitals, both as regards to coronary angiography and PCI. Likewise, patients enrolled in hospitals with catheterization laboratories underwent an invasive procedure far more frequently than patients enrolled in hospitalswithout catheterization laboratories. AmongSTEMI patients, this large difference in the useof procedures during the index hospital stay was not associated with a statistically significant improved in-hospital outcome, whether measured by in-hospital death, occurrence of congestive heart failure or length of stay, as all data for all three were very similar between the groups.
Likewise, among patients with other ACS, short-term outcomes were quite similar between the groups, with low death rates (Table 1). There were, however, some differences in short-term outcome, with a less frequent occurrence of congestiveheart failure in patients admitted to hospitals with catheterization laboratories. The length of staywas similar in community and in teaching hospitals, but was reduced in hospitals with, compared to without, catheterization laboratories.
3.2. Analysis by country
There appeared to be major geographical variations in the use of procedures for management of ACS. The baseline characteristics of patients in the three groups are summarized in Table 2. Overall, patients treated in countries with low rates of use of coronary interventions tended to have more severe baseline characteristics than patients treated in countries with intermediate or high rates of use of interventions.
There was a sharp contrast in the use of coronary angiography between groups of countries during the index hospital admission (Table 2), ranging from 9 to 84%
after STEMI and 19 to 66%
after other ACS. Likewise, the use of PCI during the index hospital stay, ranged from 8 to 67% after STEMI
and from 9 to 44% after other ACS
. Yet, despite this sharp contrast in use of invasive procedures, there was no clear difference in-hospital mortality between the groups. Congestive heart failure appeared to occur less frequently in patients from countries withintermediate rates of use of interventions. Length of stay was shortest in countries using fewerinterventions.
3.3. Analysis by use of procedures
The patient population was divided according to the use of interventional procedures (i.e. use of PCI, coronary angiography or neither). Patient groups differed by a number of baseline characteristics: the main differences were that patients undergoing intervention were younger, more frequently males, had a more frequent history of prior percutaneous intervention and received more lipid-lowering drugs than patients who underwentneither angiography nor PCI. There were also fewer high-risk patients in the groups, which underwent intervention than in those who did not (Table 3). Among patients with STEMI, there was no significant difference in death or congestive heart failure between the patients who underwent invasive procedures and those who did not (Fig. 1;comptd;;center;stack;;;;;6;;;;;width> ). The latter had a shorter length of stay. Conversely, among patients with other ACS, patients who did notundergo invasive procedures fared consistently worse than patients who did, with a higher riskof death and in-hospital congestive heart failure, albeit with a shorter length of stay (Fig. 2;comptd;;center;stack;;;;;6;;;;;width> ).

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Fig. 1 Outcomes as a function of use of procedures for STEMI. CHF, congestive heart failure; LOS, length of stay (in days); PCI, percutaneous coronary intervention.
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Fig. 2 Outcomes as a function of use of procedures for other ACS. CHF, congestive heart failure; LOS, length of stay (in days); PCI, percutaneous coronary intervention.
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3.4. Determinants of use of invasive procedures
Multivariate analysis showed that the main predictors of the use of PCI during the index hospital stay for both STEMI patients and other ACS patients were the country rate of use of PCI, and admission to a hospital performing PCI. Some other patient characteristics, such as younger age were weaker predictors of the use of PCI, but the patients' risk for adverse events, as measured by the simplified TIMI-risk score, was not associated with the performance of PCI, even when forced into the logistic model (Table 4).
3.5. Impact of invasive procedures on outcomes
Logistic regression analysis, adjusting for the baseline characteristics of the patients, the treatments received, the type of hospital and countryshowed that there was no association between the performance of PCI during the index hospital stay and survival for patients with STEMI (Table 5). Conversely, for patients with other ACS, theindependent predictors of in-hospital mortality were the simplified TIMI-risk score and the lack of in-hospital PCI (OR: 3, 75;
).
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4. Discussion
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The role of invasive procedures in ACS has been the subject of intense debate. Several clinical trials in non-STEMI have yielded conflicting results, related largely to methodological differences.11,12 Recently; two large-scale trials comparing early intervention with initial medical management13,14 provided unequivocal results demonstrating that in the current era of improved pharmacological and interventional therapies, routine use of early intervention is associated with superior 6-month and 1-year clinical outcomes15 compared to initial medical management, especially among high-risk patients. In STEMI, the optimal rates of use of coronary angiography and PCIs remain unknown. Several clinical trials have shown no benefit of systematic angiography and revascularization over initial medical management following thrombolysis.12,16,17 However, with improved percutaneous techniques and adjunctive therapies, there is atrend towards increasing early use of coronaryintervention in that setting.18
However, regardless of the outcomes of clinical trials, the actual use of interventional procedures in real practice is still markedly heterogeneous, due to differences in the availability of catheterization facilities, differences in coverage andreimbursement and healthcare organization (e.g. fee for service as opposed to per capita spending), and international differences.
This analysis from the ENACT registry uses recent PanEuropean data to explore these wide variations in the use of interventional procedures. The results show the major impact of the type of hospital and the availability of catheterization facilities on the use of invasive procedures for all types of ACS patients. In addition, geographic variations (and presumably preferences in each participating center) appear to account for even more striking differences in the use of invasive procedures.Although our analysis should be interpreted with caution, as it focused only on in-hospital outcomes, it is disturbing that a four-to eight-fold difference in the use of PCI between participating centers was not associated with reduced mortality.
Ideally, interventions should be targetedtowards high-risk patients, while patients in whom non-invasive risk stratification identifies a low risk of adverse events are unlikely to derive a major clinical benefit from invasive interventions. In that context, it is important to note that the two most important factors, which predicted the performance of in-hospital PCI were the country habitsas measured by the overall rate of interventionsin participating centers from that country andthe availability of PCI facilities. The risk scoreof the patients, defined using the simplified modelderived from the TIMI11B trial, was not anindependent predictor of PCI, confirming previous reports that the patient's risk does not drive the use of PCI.5 This is a disturbing finding indicating that, despite availability of clinical, ECG and biochemical tools, risk stratification is not currently implemented to select candidates for PCI.
When logistic regression analysis of predictors of in-hospital survival is performed, allowing to adjust for differences in patients baseline characteristics, prior medical history, pre-hospital and in-hospital therapy, hospital and country characteristics, the results differ between patients with STEMI and patients with other ACS: after STEMI, the performance of PCI during the index hospital stay has no apparent impact on hospital survival. Although short-term follow-up may be inadequate to identify the benefits of PCI, this is consistent with previous randomized trials examining the impact of routine PCI following thrombolysis, which suggested that the routine or indiscriminate use of PCI in this setting is probably unnecessary and may even be harmful, regardless of the fact whether it is performed on an urgent basis1921 or as an elective procedure.17,16 From the currently available trials, it would appear that PCI in this setting is beneficial mostly in patients with persistent occlusion of the infarct related artery where rescue PCI can be implemented in a timely fashion in the acutesetting22,23 or in the patients with evidence of inducible or spontaneous ischemia.24 It is likely that the rest of the patients, who presumably represent the majority of patients with STEMI, are at a lower risk of adverse events and therefore it explains as to why these patients do not appear to derive an obvious early benefit from routine PCI.
Conversely, among patients with other forms of ACS, logistic regression analysis indicates that the performance of in-hospital PCI is an independent predictor of survival. Again, this is consistent with the current evidence13,14 suggesting the benefitof early revascularization in this subset of ACS patients, despite the fact that in ENACT the rate of use of intravenous GpIIb/IIIa receptor blockers was low (7%). Yet, the very wide geographical variations in use of PCI in these patients with non-ST-segment elevation ACS, with a range of 14, suggest that while there is an overall benefit of PCI in this population, there is likely to be an important role for risk stratification in trying to identify the best candidates for PCI, rather than performing indiscriminate and often, possibly, unnecessary procedures. The use of simple clinical scores25,26 aswell as biochemical markers27 may be useful in ensuring more homogenous and standardized criteria for performing procedures in ACS patients,28 thereby ensuring a more efficient use of economic resources.
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5. Limitations of the study
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The present analysis suffers from several limitations: voluntary participation in this registry may have resulted in recruitment bias; only a limited number of baseline variables were collected and are available for adjustment of the potential differences between hospitals or countries. Considering the limited number of participating sites percountry, rates of use of interventions in participating centers may not reflect accurately those of the whole country. However, the marked differencesin the use of procedures between participating centers do reflect very different practice patterns, which cannot be ascribed to actual differences in patient risk profile. Finally, the ENACT registry did not incorporate information regarding outcomes, following hospital discharge. It is quite likely that the clinical benefit associated with interventional procedures is most apparent several weeks or months after the index hospital stay, as was the case in several trials comparing intervention with medical management.13,14 Therefore it is conceivable that the current analysis may underestimate the clinical benefit of early intervention on medium or long-term clinical outcomes.
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6. Conclusions
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There is considerable variation in the use ofangiography and PCI among patients with ACS. In ENACT, these differences appeared related more to geographical variations in practice patterns andto hospital type (in particular availability of PCI facilities) rather than to patient type, risk or outcome. Among patients with STEMI, the indiscriminate use of PCI during the index in-hospital staydid not appear to be associated with improved in-hospital survival. Conversely, among patients with other ACS, PCI was an independent predictor of in-hospital survival. These results emphasize the need for further research to optimize resource utilization and outcomes in this patient population. In particular, it would appear important to promote the use of risk stratification, and there is a need for more unified criteria, across hospitals as well as across countries in Europe, for selecting candidates for procedures.
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Acknowledgments
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The authors are indebted to the participants9of the ENACT Survey. In addition, the authorsare grateful for logistical support from Medical Action Communications-UK, and specificallyChristine Drewienkiewicz. ENACT was supportedby an educational grant from ScheringPloughpharmaceuticals.
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