Author + information
- Received October 24, 2016
- Accepted November 17, 2016
- Published online March 6, 2017.
- Damian Kawecki, MD, PhDa,∗ (, )
- Marek Gierlotka, MD, PhDb,c,
- Beata Morawiec, MD, PhDa,
- Michał Hawranek, MD, PhDb,c,
- Mateusz Tajstra, MD, PhDb,c,
- Michał Skrzypek, PhDc,d,
- Wojciech Wojakowski, MD, PhDe,
- Lech Poloński, MD, PhDb,c,
- Ewa Nowalany-Kozielska, MD, PhDa and
- Mariusz Gąsior, MD, PhDb,c
- a2nd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
- b3rd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
- cDepartment of Science, Training and New Medical Technologies, Silesian Center for Heart Diseases, Zabrze, Poland
- dDepartment of Biostatistics, School of Public Health in Bytom, Medical University of Silesia, Katowice, Poland
- e3rd Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
- ↵∗Address for correspondence:
Dr. Damian Kawecki, 2nd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland, M. Sklodowskiej-Curie 10, 41-800 Zabrze, Poland.
Objectives This study sought to assess the influence of direct admission versus transfer via regional hospital to a percutaneous coronary intervention (PCI) center on time delays and 12-month mortality in ST-segment elevation myocardial infarction (STEMI) patients from a real-life perspective.
Background Reduction of delays to reperfusion is crucial in a STEMI system of care. However, it is still debated whether direct admission to a PCI center is superior to interhospital transfer in terms of long-term prognosis. The authors hypothesized that compared with interhospital transfer, direct admission shortens the total ischemic time, limits the loss of left ventricular systolic function, and finally, reduces 12-month mortality.
Methods Prospective nationwide registry data of STEMI patients admitted to PCI centers within 12 h of symptom onset and treated with PCI between 2006 and 2013 were analyzed. Patients admitted directly were compared with patients transferred to a PCI center via a regional non–PCI-capable facility in terms of time delays, left ventricular ejection fraction (LVEF), and 12-month mortality. Data were adjusted using propensity-matched and multivariate Cox analyses.
Results Of the 70,093 patients eligible for analysis, 39,144 (56%) were admitted directly to a PCI center. Direct admission was associated with a shorter median symptoms-to-admission time (by 44 min; p < 0.001) and total ischemic time (228 vs. 270 min; p < 0.001), higher LVEF (47.5% vs. 46.3%; p < 0.001), and lower propensity-matched 12-month mortality (9.6% vs. 10.4%; p < 0.001). In propensity-matched multivariate Cox analysis, direct admission (hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.01 to 1.11) and shorter symptoms-to-admission time (HR: 1.03; 95% CI: 1.01 to 1.06) were significant predictors of lower 12-month mortality.
Conclusions In a large, community-based cohort of patients with STEMI treated by PCI, direct admission to a primary PCI center was associated with lower 12-month mortality and should be preferred to transfer via a regional non–PCI-capable facility.
- 12-month mortality
- acute myocardial infarction
- interhospital transfer
- primary PCI
- STEMI networks
- time delays
ST-segment elevation myocardial infarction (STEMI), the most unfavorable type of acute coronary syndrome, is associated with high risk of death and development of heart failure. Its prognosis depends on the infarct size, which is correlated with the time from the onset of symptoms to reperfusion. Consequently, constant efforts are exerted worldwide to maximally reduce the ischemic time and initiate appropriate treatment as early as possible. The main focus in this setting has been shifted from in-hospital to pre-hospital delays (1,2). Primary percutaneous coronary intervention (PCI) is the treatment with the highest level of recommendation for STEMI. However, despite the increasing number of PCI centers, regional, non–PCI-capable hospitals are often involved in the system of care. The influence of interhospital transfer and related time delays on outcomes in STEMI have been the focus of attention in Europe and the United States (3–5). Many doubts have arisen concerning interhospital transfers (6) and consequently, numerous national initiatives that address monitoring and reducing transfer-related delays have been introduced (7–11). Recently released results of the largest national program of STEMI care prove the efficacy of improving coordinated management protocols as a strategy to increase the proportion of patients treated within the preferred limits of time (12). However, efforts to constantly reduce delays to primary PCI centers remain a matter of debate (13), despite results showing that early versus late administration of thrombolysis results in a reduction in mortality (14). Although interhospital transfer accounts for a substantial postponement of reperfusion and subsequent myocardial damage (6,15), several trials showed no difference in the clinical outcomes of patients transferred between hospitals or admitted directly for PCI (4,16–18).
Considering this discrepancy in outcomes, we aimed to assess the influence of direct admission versus transfer via regional hospital to a primary PCI center on time delays, early outcomes and 12-month mortality from a real-life perspective in a large population of STEMI patients treated by PCI procedures. We hypothesized that compared with interhospital transfer, direct admission to PCI centers would substantially shorten the total ischemic time and, as a consequence, limit the loss of left ventricular systolic function and reduce 12-month mortality.
The PL-ACS registry
We analyzed the data of STEMI patients from the PL-ACS registry (Polish registry of Acute Coronary Syndromes), which is an ongoing, prospective, observational, nationwide registry of consecutive patients hospitalized with acute coronary syndromes (ACS) in Poland. It was a joint initiative of the Silesian Center for Heart Diseases and the Polish Ministry of Health. The registry’s methodology and analyses for STEMI patients concerning time delays have been previously published (19–21). In brief, all admitted patients with suspected ACS were screened for their eligibility to enter the registry, but they were not enrolled until ACS was confirmed. STEMI was defined as the presence of both: 1) ST-segment changes on electrocardiogram (ECG) consistent with an infarction, that is, an elevation of ≥2 mm in the contiguous chest leads and/or ST-segment elevation of ≥1 mm in 2 or more standard leads or new left bundle branch block; and 2) positive cardiac necrosis markers. The skilled physicians who were in charge of each individual patient collected the data. Internal checks for missing or conflicting data and values markedly out of the expected range were implemented using the registry software. In the Silesian Centre for Heart Diseases data management and analysis center, further checks were applied if necessary. If the patient was transferred via regional hospital to a primary PCI center and both hospitalizations were reported, they were combined into 1 record for the final data management.
The sample for the current analysis was patients hospitalized between January 1, 2006, and December 31, 2013. The inclusion criteria were STEMI presentation on admission and PCI as the final method of treatment. The exclusion criteria were non–ST-segment elevation ACS presentation on admission, time from onset of symptoms to admission to PCI center longer than 12 h or missing data on the time delays. The following time points (exact date and time) were available in the registry: onset of symptoms, admission to the PCI center, and first balloon inflation. For each patient, the time of the onset of symptoms was reported to the registry by the treating physician who obtained detailed information based on clinical interview with the patient, patient’s family, or medical staff members present at the first medical contact in case of communication problems with the patient. According to this, the following time delays were calculated: onset of symptoms to admission, admission to PCI, and onset of symptoms to PCI. According to the protocol, left ventricular ejection fraction (LVEF) was defined as the latest available measure, preferably just before discharge, from echocardiography. The vital status at 12 months was obtained from the official mortality records from the government databases and was available for all patients with an exact date of death.
Patients were stratified and analyzed in 2 groups: those directly admitted to a PCI center and those transferred from another non–PCI-capable facility to a PCI center. Directly admitted patients were those reaching a PCI center directly from the place of onset of symptoms by means of an emergency medical system or reaching a PCI center by themselves. Direct transfer to PCI center and interhospital transfer were identified according to a dedicated field in the registry dataset.
The main outcome measure considered was 12-month mortality. Secondary outcomes measures were pre-hospital, in-hospital, and total time delays; LVEF; and in-hospital and 30-day mortality.
The data are presented as counts and percentages, mean ± SD, or medians and interquartile ranges (IQRs) and were compared between the groups with the Student t test, the Mann-Whitney U test, or the chi-square test with respect to data type and its distribution. Long-term survival was analyzed with the Kaplan-Meier method and compared with the log-rank test. Multivariate logistic regression and Cox proportional hazard regression models were used to analyze the influence of admission strategy (direct or transfer) on in-hospital and 12-month mortality. Two models were defined. The baseline model (baseline and clinical characteristics on admission) included the following variables: type of admission (direct or transfer), year of admission, age, sex, smoking, hypertension, diabetes, obesity, prior acute myocardial infarction (AMI), prior PCI, prior coronary artery bypass grafting, anterior STEMI (versus other ECG localizations), pre-hospital cardiac arrest, Killip class 3, Killip class 4 on admission, and initial ECG pattern (sinus rhythm, atrial fibrillation, pacing, and right or left bundle branch block). The second model included all variables from the baseline model plus the time from the onset of symptoms to admission to a PCI center.
Furthermore, for better control of selection and clinical bias, a propensity score method was used to match the groups for the year of admission and all baseline characteristics and parameters listed in Table 1. The package MatchIt, available in R (R Foundation for Statistical Computing, Vienna, Austria), was used for the nearest neighbor matching method with the distance option set to “logit” and caliper to 0.1. All analyses were then recalculated for the propensity-matched cohorts.
A p value <0.05 was considered the level of significance for all analyses. Statistics were calculated with STATISTICA 10 (Statsoft, Tulsa, Oklahoma), IBM SPSS Statistics version 22 (SPSS, Chicago, Illinois), and R statistical package, version 2.15.3 (R Foundation, Vienna, Austria).
Of the 132,715 STEMI patients from the PL-ACS registry, 70,093 were included in the analysis on the basis of the inclusion and exclusion criteria (Figure 1). From the studied population, 39,144 (55.8%) patients were admitted directly to a primary PCI center, and 30,947 (44.2%) were transferred to a primary PCI center via a regional non–PCI-capable facility. The proportion of direct admissions increased significantly over time and reached 68% in 2013 (Figure 2). There were no sex or age differences between the groups. Patients transferred from non–PCI-capable facilities had higher rates of cardiovascular risk factors (hypertension, diabetes, obesity), prior AMI, and worse clinical presentations, with more frequent pre-hospital cardiac arrest, anterior AMI, and Killip classes 3 or 4 on admission. Despite being statistically significant, these differences in the clinical and baseline characteristics were small in absolute numbers (Table 1). Transferred patients were admitted to primary PCI centers with significantly longer delays (absolute difference of median onset of symptoms to admission time was 44 min; p < 0.001); however, they had a shorter median admission-to-PCI time than patients admitted directly, by 4 min (Table 1, Figure 3). This resulted in a significantly longer median time from the onset of symptoms to PCI (270 min [IQR]: 180 to 420 min] compared with 228 min [IQR: 156 to 378 min] in the direct admission group; p < 0.001). Among patients admitted directly, 13.6% had PCI performed in <2 h from the symptom onset, compared with 9.0% of patients transferred from regional hospitals.
Data on the major medications used during the hospital stay and PCI procedures are shown in Table 2. Glycoprotein IIb/IIIa receptor inhibitors were more frequently used in patients admitted directly, whereas P2Y12 receptor antagonists, beta-blockers, angiotensin-converting enzyme inhibitors and statins were administered more often to transferred patients. The need for diuretic administration in the acute phase was similar in both groups (18% of patients; p = 0.62). Total or subtotal occlusion of the infarct-related artery on initial coronary angiogram was present more frequently among patients admitted directly; however, the reperfusion success measured by final Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was achieved with equal frequency in both groups and was approximately 92%.
LVEF was significantly higher in patients admitted directly than in transferred patients (47.5 ± 10.2% vs. 46.3 ± 10.4%, respectively; p < 0.001). Comparison of in-hospital adverse events revealed higher rates of target vessel revascularization in transferred patients, with similar incidence of stroke, major bleeding complications, and resuscitated cardiac arrest in both groups (Table 3). In-hospital mortality was slightly higher in patients admitted directly (by 0.3%). Later, after 30 days, 6- and 12-month mortality was higher among transferred patients with an absolute difference at 1 year of 0.9% in favor of direct admissions (Table 3, Figure 4).
In multivariate models regarding the in-hospital period, interhospital transfer was significantly associated with lower mortality after adjustment for baseline and clinical characteristics, and for the onset of symptoms to admission time (Table 4). Conversely, in both multivariate models of 12-month mortality, it was a significant predictor of higher mortality.
In a 1:1 match, 76% of patients admitted directly (29,624 from 39,144 patients) were matched with 96% of patients transferred (29,624 from 30,947 patients). The baseline characteristics in the matched cohort were well-balanced between the groups admitted directly and transferred, with no statistically significant differences (Table 1, Figure 2). The in-hospital and 12-month outcomes and the multivariate models for the matched cohort are presented in Tables 3 and 4 and Figures 3 and 4. The results achieved for the matched cohort were similar to those described for the entire cohort of patients.
The main finding of this study from the real-life registry is a 12-month mortality benefit after direct admission to PCI center as compared with interhospital transfer in an unselected cohort of STEMI patients undergoing primary PCI. Interhospital transfer to PCI was identified as a predictor of higher 12-month mortality after adjustment for baseline characteristics and time from onset of symptoms to reperfusion in the entire cohort and additionally after propensity-score matching. By contrast, direct admission to a primary PCI center was associated with shorter time delays to PCI, higher LVEF, and lower rates of 1-year mortality. Longer time to reperfusion was previously described as a risk factor for adverse outcome independent of admission strategy (22). We have shown that both factors, interhospital transfer and longer time to reperfusion, might contribute independently and additively to higher mortality, most probably via diminished preservation of left ventricular systolic function.
The contrary results of equal rates of mortality in patients admitted directly and transferred were reported previously in randomized controlled trials (4,15–18). It was postulated that no difference in outcome between patients admitted directly or transferred could be explained by late presentation, exceeding the optimal 60 to 120 min from onset of symptoms, when time to reperfusion is critical for outcome (15,23). During this time window, the mortality benefit decreased with time (24). In the PL-ASC registry, time delays to primary PCI are still prolonged despite a constant increase in the density of catheter laboratories in the STEMI network, which doubled between 2006 and 2013 from 1.7 to 3.9 per million inhabitants in a country with a population of approximately 38 million. As a result, in more than 90% of cases, the distance to the nearest primary PCI center is <90 km, and 748 primary PCI procedures per million inhabitants were performed in Poland in 2013. Regardless of the continuous optimization of invasive treatment and the high incidence of AMI (25), transport to a primary PCI center remains one of the major phases and concerns of STEMI care because the majority of patients in both groups in the current analysis were treated outside the timespans required for the greatest impact of reperfusion on myocardial salvage. However, the adjusted data indicate that even over these timespans, a shorter time to reperfusion results in better outcomes, according to the hypothesis of LVEF preservation with the shortening of total ischemic time.
The lower in-hospital mortality of patients transferred via regional hospital to a PCI center requires a brief comment. This outcome measure was studied previously in regard to interhospital transfer and was found to be equal in patients transferred and admitted directly (22,26). In our cohort, patients transferred to a PCI center had better in-hospital survival despite a worse baseline clinical profile and also after adjustments. Of note is the lower rate of initial TIMI flow grade 0 or 1 among transferred patients; however, PCI was equally successful in both groups, as measured by the final TIMI flow grade 3. This paradoxical finding of lower in-hospital mortality in transferred patients could be affected by the bias caused by the longer delay of reaching the PCI hospital, causing a higher proportion of patients to die before PCI could be performed compared with patients admitted directly. As a result, the transferred group may be positively pre-selected. Nevertheless, the rates of mortality were inverted in the post-discharge period, with a higher mortality in transferred patients at 30 days and at 12 months.
Another general point emerging from the study is the high proportion of direct admissions, exceeding 50%, compared with approximately one-third reported in previous trials and registries (6,15,16). Starting with a 70% rate of fibrinolysis in the late 1990s (27), consistent efforts to increase the quality of STEMI care in Poland, increase in the density of PCI-capable centers, well-established education of invasive cardiologists, subsequent increase in PCI centers working in a 24/7 system, and finally introduction of pre-hospital ECG transfer directly from an ambulance to a PCI center, resulted in the current marginal rates of thrombolysis and high rates of primary PCI. Mainly the latter (ECG transfer) is responsible for high percentage of direct admissions to PCI canters in our country. As a result, the crude rates of 30-day and 12-month mortality in our registry are comparable to or even lower than those reported world-wide, either in real-life studies or randomized controlled trials, taking into account that high-risk patients were not excluded from our study (6,16,28,29).
The major aim of all initiatives to improve STEMI care is to maximally shorten the delay from the onset of chest pain to reperfusion because there is a correlation between a longer delay to reperfusion and the subsequent increase in infarct size (6) and mortality (30). Our study, based on this hypothesis, shows the importance of the pre-PCI strategy in shortening the ischemia time. The between-groups difference in admission-to-PCI time was significant but accounted for only a 4-min longer median delay in patents admitted directly than in those that were transferred. Therefore, the calculated difference in total ischemic time may be attributable exclusively to the pre-PCI center delay. Considering this, direct admission for primary PCI seems to be the preferred strategy for reduction of total time delays in STEMI. If direct admission is unavailable, efforts should be focused on maximal shortening of the delay related to peripheral hospitals (door-in door-out time) as an alternative target to reduce delays (31).
For the current analysis, we attributed longer delays in the transferred groups entirely to the fact that the patient was transferred, whereas patient-related delays, unavailable for the analysis, could balance the difference in time to arrival at the primary PCI center. Additionally, considering transfer from a peripheral hospital as a risk factor, we cannot provide insights into the partial influence of its components in the worsening of outcomes. Information on the time of the first medical contact, time of arrival to peripheral hospital, the door-in door-out time, and delay related to transport service were unavailable for the analysis. Finally, the data on the clinical course of patients from the pre-primary PCI period were unavailable for the analysis and resulted in blanking of a subset of patients who died in a peripheral hospital before reaching a PCI center. This could result in additional selection bias in the transfer group, making this group rather positively than negatively pre-selected. Therefore, it should not influence the obtained results.
In a large, community-based cohort of patients with STEMI treated by PCI, direct admission to a primary PCI center was associated with lower 12-month mortality and should be preferred to transfer via a regional non–PCI-capable facility.
WHAT IS KNOWN? Reduction of delays to reperfusion is crucial in a STEMI system of care. However, it is still debated whether direct admission to a PCI center is superior to interhospital transfer in terms of long-term prognosis.
WHAT IS NEW? Direct admission to a primary PCI center seems to be better than involvement of a regional hospital and subsequent transfer for primary PCI and should be considered the preferred strategy in all STEMI cases.
WHAT IS NEXT? Transfer for primary PCI from regional hospitals cannot be eliminated from the STEMI system of care in the near future. Therefore, further analyses focused on patients being transferred should address the opportunities for maximal shortening of delays at the level of regional hospitals and transport services.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- acute coronary syndrome(s)
- acute myocardial infarction
- interquartile range
- left ventricular ejection fraction
- percutaneous coronary intervention
- ST-segment elevation myocardial infarction
- Thrombolysis In Myocardial Infarction
- Received October 24, 2016.
- Accepted November 17, 2016.
- American College of Cardiology Foundation
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