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European Heart Journal Advance Access published online on January 22, 2007
European Heart Journal, doi:10.1093/eurheartj/ehl471
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Effects of revascularization within 14 days of hospital admission due to acute coronary syndrome on 1-year mortality in patients with previous coronary artery bypass graft surgery

Claes Held1,*, Per Tornvall1 and Ulf Stenestrand2

1 Karolinska Institutet, Department of Medicine, Unit of Cardiology, Karolinska University Hospital, 171 76 Stockholm, Sweden
2 Department of Cardiology, University Hospital of Linköping, Sweden

Received 23 May 2006; revised 21 November 2006; accepted 21 December 2006.

* Corresponding author. Tel: +46 8 5177 9286; fax: +46 8 32 45 97. E-mail address: claes.held{at}karolinska.se


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusions
 Appendix A
 Acknowledgements
 References
 
Aims To determine whether revascularization within 14 days reduces 1-year mortality in patients with a previous CABG admitted for non-ST-elevation ACS. Current guidelines for patients with acute coronary syndrome (ACS) include early revascularization. The evidence is derived from studies, in which patients with previous coronary artery by-pass graft (CABG) surgery often were excluded and thus insufficient to support a similar strategy in these high-risk patients in whom coronary interventions are associated with lower success and higher complication rates.

Methods and results A cohort of 10 469 patients <80 years old from a national registry, admitted to coronary care units in Sweden, was studied. We obtained 1-year mortality data from the Swedish National Cause of Death Registry. Relative risk (RR) in patients undergoing revascularization within 14 days (n = 4269) of admission compared to those who did not (n = 6200) was calculated by using multivariable logistic regression analyses and propensity scores for the likelihood of early revascularization. At 1-year, unadjusted mortality was 5.4% in the revascularized group and 13.1% in the conservatively treated group. In multiple regression analyses, revascularization was associated with a reduction of 1-year mortality (RR 0.67; 95% CI, 0.56–0.81; P < 0.001).

Conclusion In patients with a previous CABG admitted for ACS, revascularization within 14 days of hospital admission was associated with a marked reduction in 1-year mortality, supporting an early invasive approach also in this subset of patients.

Key Words: Acute coronary syndrome • Invasive strategy • Revascularization


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusions
 Appendix A
 Acknowledgements
 References
 
During the last decade, great improvement has been made in the treatment of the acute coronary syndrome (ACS). Today, pharmacological treatment includes aspirin, clopidogrel, cardioselective beta-blockers, long-acting nitrates, low-molecular-weight heparin, and often glycoprotein IIb/IIIa inhibitors. Recently, three large randomized studies1–3 have been consistent in showing benefit of an early invasive strategy, in addition to the pharmacological treatment. The FRISC II study1 showed that patients treated invasively had a reduction in the combined endpoint of non-fatal myocardial infarction (MI) and death at 6 months. The RITA 33 and TACTICS-TIMI 18 studies2 showed reductions in rehospitalization for unstable angina pectoris (UAP), non-fatal MI, or death at 4 and 6 months, respectively. The benefit was consistent also after 2 years follow-up of the FRISC II patients.4 A recent meta-analysis of patients with ACS5 concluded that a selective invasive approach was beneficial in reducing non-fatal MI, degree of angina pectoris and all-cause rehospitalization, with trends towards lower mortality during follow-up, despite somewhat higher early in-hospital mortality. In contrast, the most recent randomized study (ICTUS) comparing early invasive strategy to selectively invasive management could not demonstrate a reduction in the primary outcome (death, non-fatal MI, or rehospitalization for angina) in patients with non-ST-elevation MI (NSTEMI).6

An increasingly common group of ACS patients are those with a previous coronary artery bypass graft (CABG) operation. However, in FRISC II and RITA 3, previous CABG was an exclusion criterion, and in the TACTICS-TIMI 18 and ICTUS trials, few patients in total were included. Thus, the evidence base for a clinical benefit of an invasive strategy in this subgroup is missing. Despite the lack of data, patients are often treated accordingly, including early coronary angiography often followed by a revascularization.

Coronary angiography of patients with a previous CABG operation is associated with an increased risk of complications. Selective angiography of the left internal mammary artery via the left subclavian artery might further increase the risk of stroke during catheterization. In addition, intervention on vein grafts is associated with decreased success rates, increased complications, and higher restenosis rates compared with angioplasty of native coronary arteries.7–9 Complication rates tend to increase with the time delay from the previous surgery.7–10 Thus, the risk–benefit ratio may differ in this high-risk subset of ACS patients.

Since randomized studies are lacking and subgroup analyses of the published ACS studies are likely to be underpowered, it is important to evaluate other available data. Data from the GRACE registry11 on patients with previous CABG surgery indicated that an early invasive approach (<48 h) did not improve outcome in terms of in-hospital or 6-month post-discharge death, rehospitalization for heart disease, or non-fatal reinfarction. Conversely, it was associated with increased risk of major bleeding, including haemorrhagic stroke.

Results from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admission (RIKS-HIA) have previously confirmed that patients with ACS benefit from an invasive strategy including revascularization within 14 days of admission.12 The hypothesis of the present study was that revascularization <14 days in patients with a previous CABG operation admitted for UAP or NSTEMI might not be associated with a mortality benefit. We therefore evaluated the clinical outcome of revascularization within 14 days of hospital admission in comparison with no or later (>14 days of admission) revascularization, in a large cohort from the RIKS-HIA registry.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusions
 Appendix A
 Acknowledgements
 References
 
RIKS-HIA includes all patients admitted to the coronary care units of participating hospitals (~95% of all hospitals in Sweden). Information is reported on case record forms including 100 variables, which have been described elsewhere.13 The full protocol is available at www.riks-hia.se. Data verification was performed by comparing entered data in RIKS-HIA with hospital records of 3020 randomly chosen patients at 63 different hospitals, showing an average agreement of 95%. Previous history of stroke, dementia, renal failure, congestive heart failure (HF), peripheral artery disease, chronic pulmonary disease, or cancer were obtained by merging with the National Patient Registry, which includes diagnoses on all patients hospitalized in Sweden from 1987 and forward. One-year mortality data were obtained by merging the RIKS-HIA database with the National Cause of Death Registry, including the vital status of all Swedish citizens in 1991 through 2005. The cause of death had only been updated until last of December 2003. All patients for whom data were entered into the RIKS-HIA were informed of their participation in the registry (patients could request to be excluded from the registry). The registry and the merging with the registries were approved by an ethics committee and the National Board of Health and Welfare. After merging the registries, all patient identifications were removed from the data file. Only data from patients in the RIKS-HIA registry between 1991 and 2004, with a history of previous CABG, and a discharge diagnosis of NSTEMI or UAP and age below 80 years were included in the study. The criteria for the diagnosis of MI were standardized and identical for all participating hospitals.14,15 The diagnosis of unstable angina pectoris required typical symptoms and ST-segment fluctuation on ECG or elevation of biochemical markers above the normal limit. The primary endpoint was all cause mortality at 1 year. Secondary endpoints were all-cause mortality at 30 days, cardiac death at 1 year and re-admission for MI within 1 year.

Statistics
The two patient groups were compared by {chi}2 tests for categorical variables and by t-test for continuous variables, all tests were two-sided. A propensity score16,17 was calculated for each patient to estimate the probability of belonging to the early revascularization group (compared with not having revascularization performed within 14 days) given the background characteristics and treatments received. Adjusting for the propensity score in the analysis aimed to balance the groups regarding differences in background characteristics, which also leads to a simpler model with higher precision of parameter estimates. A multiple logistic regression model was fitted to estimate the propensity score, where initially 45 variables were tested including multiple interactions. Variables that were clinically judged to have little influence and did not affect the likelihood of early revascularization in the statistical test models were excluded. The final model included 26 covariates: age (as a second degree polynomial), sex, current smoker, history of percutaneous coronary intervention (PCI), previous MI, history of diabetes mellitus, history of stroke, HF, peripheral artery disease, renal insufficiency, chronic pulmonary disease, dementia, cancer within 3 years, medications before study entry (including beta-blockers, diuretics, lipid-lowering drugs, and long-acting nitrates), circulatory arrest at arrival, Killip class on arrival, early interventions in hospital (including intravenous or subcutaneous heparins, intravenous beta-blockers, intravenous nitroglycerin), symptoms of HF during hospital stay, admission year, in-house catheterization laboratory, and teaching hospital status. Different models of multivariable logistic regression analyses were used to identify if revascularization <14 days of admission was associated to 1-year mortality. The first model (A) was used mainly to study the association of early revascularization to early in-hospital mortality and included the propensity score as the only covariate. The second logistic regression model (B) included the propensity score and discharge prescriptions (oral anticoagulants, aspirin, thienopyridines, beta-blockers, diabetes medication, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, calcium-channel blockers, digitalis, diuretics, lipid-lowering drugs, and long-acting nitrates). Stratification was done for clinically relevant subgroups and the logistic regression model was tested in each subgroup, including inclusion from different survival points. The main models were based on 14-day survivors. In addition, models with all patients, including those who died before day 14 were used to confirm that revascularization was not associated with early excess in-hospital mortality. For patients who had a missing value in one of the variables included in the propensity score, a separate sensitivity analysis by logistic regression analysis was performed including age, gender, previous MI, history of diabetes mellitus, history of stroke, HF, peripheral artery disease, renal insufficiency, chronic pulmonary disease, dementia, and cancer within 3 years.

The large number of missing data regarding glycoprotein IIb/IIIa-inhibitors is due to the fact that they were not introduced in Sweden until 1998. Thus, this variable was not included in the propensity score or the logistic regression analyses. For the same reason, left ventricular ejection fraction was excluded from the propensity score, as it was introduced in 1999 in the protocol. Statistical analyses were performed with the statistical program SPSS version 14 (SPSS Inc., Chicago, IL, USA).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Conclusions
 Appendix A
 Acknowledgements
 References
 
Patients and baseline characteristics
A history of CABG was present in 10 837 (8.9%) of all patients in the registry younger than 80 years old and admitted with an index discharge diagnosis of NSTEMI or UAP during the study period. The proportion of revascularization (PCI and CABG) within 14 days and corresponding 1-year mortality rates for the individual years 1995–2004 are shown in Figure 1. The 14-day mortality was 55/4324 (1.3%) among patients treated with revascularization compared with 313/6513 (4.8%) in patients treated conservatively. After adjusting for the propensity score for having a revascularization, the relative risk (RR) was 0.52 [95% confidence interval (CI) 0.38–0.73; P < 0.001] of dying within 14 days if revascularized during this time period. The remaining 10 469 patients, alive at day 14 and fulfilling the inclusion criteria constituted the main study population.


Figure 4711
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  		Figure 1 Development over the years 1995–2004 of the proportion of revascularization within 14 days by PCI and CABG, respectively, and corresponding 1-year mortality rates for revascularization <14 days vs. no or later revascularization.

 
Baseline characteristics differed between the two groups on several aspects. Those who underwent revascularization within 14 days of hospitalization were 2 years younger. The cardiovascular risk profile was more favourable, with less prevalence of active smoking, diabetes mellitus, hypertension, previous MI or stroke, and renal failure. Patients undergoing revascularization <14 days were more likely to have no or mild signs of congestive HF, i.e. Killip class I or II at admission. In addition, they were more often treated with aspirin and other platelet inhibitors, beta-blockers, calcium-channel blockers, lipid-lowering drugs, and long-acting nitrates and less often with oral anticoagulants or medication indicative of HF prior to admission. There was no difference in mean total cholesterol, LDL or HDL-cholesterol levels at baseline between those who underwent revascularization <14 days and those who did not.

To compensate for differences in baseline characteristics due to the non-randomized design, the population was stratified into propensity score quartiles (Table 1). The baseline characteristics then became almost equally distributed except for quartile 1, e.g. those with the lowest propensity to have revascularization performed within 14 days, according to their baseline profile.


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  		Table 1 Baseline characteristics and interventions in patients with NSTEMI/UAP age <80 years old and with history of a previous CABG operation and alive at day 14 divided into propensity score quartiles

 
Among surviving patients undergoing revascularization within 14 days of admission, PCI was predominant and was performed in 3962 cases (92.8%), a CABG in only 163 cases (3.8%), and both PCI and CABG in 140 cases (3.3%). In the control group, 1560 patients (25.2%) underwent subsequent revascularization during day 15–365, [PCI 1228 (78.7%), CABG 197 (12.6%), and both PCI and CABG 135 (8.7%), respectively].

The length of hospitalization did not differ; the median stay was 5 days for both groups with an inter-quartile range of 3–8 days and 3–7 days, respectively. Re-infarction rate during the initial hospital stay was greater (2.3 vs. 1.8%: P = 0.05), but re-admission due to MI during the first year was significantly less frequent (10.4 vs. 15.6%; P < 0.001) among those undergoing revascularization <14 days compared with those who did not. In patients surviving the first 14 days after hospital admission, the unadjusted mortality was significantly lower at 30 days (0.8 vs. 1.4%; P = 0.004) and at 1 year (5.4 vs. 13.1%; P < 0.001) among patients undergoing revascularization within 14 days of admission. The cause of death between days 14 and 365 did not differ between the two groups (P = 0.254), with cardiac death (67.8 vs. 70.4%), stroke (3.8 vs. 3.6%), cancer (5.1 vs. 5.2%), and other causes (13.3 vs. 18.1%) in the revascularization <14 days and control group, respectively.

Multivariable logistic regression analyses
Propensity score was used as a covariate in the multivariable logistic regression analyses. The association between the included variables and the likelihood of early revascularization is shown in Figure 2. It is of note that a more recent admission year, university hospital status, and need for i.v. or s.c. heparins or i.v. nitroglycerin increased the likelihood of a new revascularization. Conversely, older age, dementia, renal insufficiency, and previous HF were the strongest deterrents for early revascularization. The propensity score overall was strongly associated with improved survival both in model A (propensity score as covariate) with an RR of 0.06 (95% CI 0.04–0.08; P < 0.001) and in the main model (B, propensity score and discharge medication as covariates) with an RR of 0.13 (95% CI 0.08–0.21; P < 0.001), thus identifying patients with lower risk. The goodness of fit of the propensity score was evaluated by c-statistics (area under the receiver operating characteristic curve: 0.76).


Figure 4712
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  		Figure 2 Association between the covariates included in the propensity score and the likelihood of early revascularization (<14 days).

 
Patients undergoing revascularization <14 days had a lower unadjusted mortality 93/4324 (2.2%) vs. 394/6513 (6.0%) at 30 days, and the propensity score adjusted RR for death between days 0 and 30 was 0.72 (95% CI 0.56–0.94), indicating lower mortality associated to revascularization within 14 days when all patients were included. Since patients who died too quickly to undergo revascularization could burden the group without revascularization within 14 days, analysis of only 14-day survivors was performed. Whereas unadjusted 30-day mortality favoured early revascularization 38/4269 (0.9%) vs. 81/6200 (1.3%), the propensity score and discharge medication adjusted 30-day mortality was increased RR 1.62 (95% CI 1.01–2.60; P = 0.045). However, among 14-day survivors, the RR of death at 1 year was significantly reduced with an RR of 0.67 (95% CI 0.56–0.81; P < 0.001) among patients undergoing revascularization within 14 days. Table 2 shows the crude 1-year mortality by quartiles of propensity scores and the fully adjusted RR (model B) in 14-day survivors. The reduction in 1-year mortality was most pronounced within propensity score quartiles 1 and 2 (Table 2, Figure 3).


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  		Table 2 One-year mortality by propensity score quartiles in patients revascularized <14 days vs. no or later among survivors at day 14

 

Figure 4713
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  		Figure 3 Cox survival curves adjusted for propensity score and discharge medications and stratified by patients undergoing revascularization within 14 days of admission (dotted line) vs. no or later revascularization (full line), by quartiles of propensity score.

 
When the analysis was restricted to cardiac death among 14-day survivors, the mortality was 135 (3.1%) for revascularization within 14 days compared with 470 (7.5%) and adjusted cardiac death (by model B) RR was 0.73 (95% CI 0.57–0.92; P = 0.009) at 1 year.

In a sensitivity analysis including all patients between days 0 and 365, the propensity score adjusted RR for death within 1 year was 0.59 (95% CI 0.51–0.68; P < 0.001). A sensitivity analysis of the 837 patients who had a variable missing, prohibiting calculation of a propensity score, revealed that the patients revascularized within 14 days had an RR of 0.46 (95% CI 0.26–0.82; P = 0.009) of death within 1 year when adjusted for age, gender, and comorbidity. We could not establish any relation between timing of revascularization and 1-year mortality when all patients were included; revascularization within 48 h of admission RR was 0.62 (95% CI 0.47–0.82; P < 0.001), and within days 3–14, the RR was 0.62 (95% CI 0.52–0.73; P < 0.001) compared with no or later than 14 days revascularization.

Subgroup analyses
The effects of revascularization within 14 days of admission because of ACS on 1-year mortality in pre-planned selected subgroups are shown in Table 3. There was no indication of heterogeneity in risk reduction according to gender, age, smoking habits, diabetes, peripheral artery disease, or the presence of ST-segment depression. Furthermore, there was a significant risk reduction in patients with elevated biomarkers (CKMB or troponin) indicative of myocardial injury and among those with HF. Conversely, among patients with normal biomarkers and/or a discharge diagnosis of UAP, revascularization tended to be associated with an increased mortality.


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  		Table 3 Early revascularization and 1-year mortality in selected subgroups of ACS patients alive at day 14

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Conclusions
 Appendix A
 Acknowledgements
 References
 
Current European and American guidelines recommend early revascularization in addition to pharmacological therapy for patients with ACS,18,19 in high-risk individuals, and in situations where medical therapy failed. In recently published guidelines on PCI, these recommendations were underlined.20 However, for patients with a history of previous CABG, the evidence for these recommendations is lacking, since such patients were almost entirely excluded from the available studies. The main finding from this registry study is that revascularization within 14 days of hospital admission for ACS is supported also in these patients, with a significant reduction in 1-year mortality by 30%. This was despite a higher risk of peri- and post-procedural complications, indicated in our study by a higher 30-day mortality. Patients undergoing revascularization were younger and had a less advanced cardiovascular risk profile. However, the clinical benefits of this strategy remained after multiple adjustments for confounders and propensity scores. Furthermore, we noted a reduction in the re-admission rate for MI during the first year.

Data from other studies are scarce. In both the FRISC II and RITA 3 trials, patients with previous CABG were excluded. In the GUSTO IV study, evaluating the effects of abciximab, administered early in patients with ACS and NSTEMI, revascularization within 30 days was associated with an improved 1-year survival21 with an RR of 0.53 (CI 0.37–0.77) after multivariable adjustments. However, only 9% of the study population had a history of a previous CABG. Results from this subgroup were not presented. Similarly, no separate outcome data for patients with history of a previous CABG in the TACTICS-TIMI 18 and ICTUS trials are available.

Two registry studies have shown conflicting results regarding the benefit of early revascularization of ACS patients.22,23 However, these studies investigated effects of very early (<6 h) invasive vs. early conservative strategy. The latter23 did not confirm a benefit of very early compared with no revascularization. There are relevant arguments favouring a time period for medical stabilization24 and the most recent guidelines advocate angiography within 48 h for high-risk patients with NSTEMI.20 In the present study, we demonstrate a mortality reduction when interventions are performed within 14 days of hospital admission. Indeed, this benefit was consistent whether revascularization was performed in the early or later phase of this period. However, our study was not designed to evaluate the optimal timing of intervention within this time frame.

A propensity score17 was calculated to estimate the likelihood of revascularization within 14 days in our study (see Methods). The rationale for dividing the study cohort into quartiles was to simulate a randomized study by creating groups with the same likelihood of revascularization within 14 days,16 and similar baseline characteristics. This goal was well achieved in quartiles 2–4, although there still remained differences between the two groups in quartile 1. On the basis of included variables, patients within each quartile should have had the same probability to receive a revascularization <14 days. Since the baseline characteristics were not perfectly matched in quartile 1 with the lowest likelihood of revascularization (14.0%), there is a risk of overestimating the benefit of revascularization. This quartile has the highest mortality risk and the physicians have selected patients with better prognosis for a repeated revascularization. Quartiles 2 and 3 are well matched and the indicated relative reduction in 1-year mortality is most likely reliable. The patients in quartile 4 had the lowest mortality but the highest proportion of revascularization <14 days (67.6%). Both the unadjusted and the model B adjusted 1-year mortality favoured early revascularization among these lower risk patients. However, the absolute risk reduction was only a few per cent as indicated by Figure 3. This reflects a well-known selection bias to intervene in patients with a greater chance of surviving.

The reduction in mortality in our study was present across most traditional subgroups not indicating any heterogeneity. Since the reduction in 1-year mortality was more or less pronounced among these subgroups, we can identify subsets of patients who would benefit more from early revascularization: patients over 70 years, patients with diabetes, current smokers, and patients with HF. Patients with elevated biochemical markers for myocardial injury and/or ST-segment depression had a greater risk reduction from revascularization than the overall result. Patients without biochemical indication of myocardial injury seemed to have a worse outcome if revascularized, which supports the results from the FRISC II trial.25 Our analysis also confirmed that early revascularization was beneficial both in patients with and without combination therapy of ASA and thienopyridines, and thus the survival benefit from early revascularization could not be attributed to dual antiplatelet therapy.26

Limitations and strengths
Our results are based on retrospective analyses of non-randomized patients in a large cohort from a national registry. Clearly, there were differences between the groups on admission, with younger age and a more benign cardiovascular risk profile among those undergoing revascularization, reflecting a selection bias. Although we used rigorous efforts to adjust for baseline differences between patients, including propensity score matching and multivariable regression analyses, the retrospective nature of the study cannot replace a prospective randomized controlled trial. Other variables not registered, but of potential importance, such as inflammatory diseases, degree of coronary artery disease, and left ventricular ejection fraction, might have influenced the clinician's decision on revascularization, which could have affected the long-term results. Furthermore, taking the broad time window of enrolment of patients into account, the pharmacological therapy changes, which may have had an impact on outcome. However, the outcome of the disease and the benefits of treatment in real life are better estimated when all consecutive patients from a whole country are included without using the restrictive eligibility criteria of a randomized trial. Our study has the advantage of providing such a population, with a high validity in data and a complete follow-up on mortality. The homogenous results across the quartiles of propensity score and consistent findings in the subgroup analyses, comparable to other evidence-based results in patients without a previous CABG operation, strengthen the validity of our results.


   Conclusions
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
Appendix A
 Acknowledgements
 References
 
In the absence of randomized trials, our findings lend support to a strategy of revascularization within 14 days, in patients with ACS and previous CABG history, despite a higher risk of peri-procedural complications. The optimal timing of angiography and revascularization after admission still remains uncertain. Patients at higher risk seem to have the greatest long-term benefit of ~30% relative reduction in 1-year mortality. Patients with few risk indicators have minimal benefit of repeated revascularization and should not routinely be considered for revascularization. They are more likely to benefit from aggressive secondary preventive medication and lifestyle modification as the first line of therapy.


   Appendix A
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
 Appendix A
Acknowledgements
 References
 
Participating centres
Alingsås, Arvika, Avesta, Bollnäs, Borås, Danderyd, Eksjö, Enköping, Eskilstuna, Fagersta, Falun, Finspång, Gävle, Halmstad, Helsingborg, Hudiksvall, Härnösand, Hässleholm, Jönköping, Kalix, Kalmar, Karlshamn, Karlskoga, Karlskrona, Karlstad, Karolinska Huddinge, Karolinska Solna, Katrineholm, Kristianstad, Kungälv, Köping, Lidköping, Lindesberg, Linköping, Ljungby, Ludvika, Lund, Lycksele, Malmö, Mora, Motala, Mölndal, Norrköping, Norrtälje, Nyköping, Oskarshamn, Sahlgrenska Göteborg, Sala, Sandviken, Simrishamn, Skellefteå, Skene, Skövde, Sollefteå, St Görans Stockholm, Sundsvall, Säffle, Södersjukhuset Stockholm, Trelleborg, Trollhättan, Uddevalla, Umeå, Uppsala, Varberg, Visby, Värnamo, Västervik, Västerås, Växjö, Ystad, Ängelholm, Örebro, Örnsköldsvik, Östersund, Östra Sjukhuset Göteborg.


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
 Appendix A
 Acknowledgements
References
 
The RIKS-HIA registry has been supported by grants from the Swedish Association of Local Authorities and Regions, National Board of Health and Welfare, and the Swedish Heart-Lung Foundation. We would like to thank all the participating hospitals in Sweden for their help and co-operation to contribute with data to RIKS-HIA. U.S., C.H., and P.T. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of interest: none declared.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
 Appendix A
 Acknowledgements
 References
 

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A. Hirsch, F. Windhausen, J. G.P. Tijssen, A. J.M. Oude Ophuis, W. J. van der Giessen, P. M. van der Zee, J. H. Cornel, F. W.A. Verheugt, R. J. de Winter, and for the Invasive versus Conservative Treatment in
Diverging associations of an intended early invasive strategy compared with actual revascularization, and outcome in patients with non-ST-segment elevation acute coronary syndrome: the problem of treatment selection bias
Eur. Heart J., March 2, 2009; 30(6): 645 - 654.
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