Keywords
INTRODUCTION
Non-ST segment elevation acute coronary syndrome (NSTEACS) is the principal cause of admission in patients with coronary heart disease.1,2 Numerous studies have established the efficiency of antithrombotic therapy for this condition as well as the importance of risk stratification at admission and prior to discharge.3-6 Despite this, marked differences continue to appear in the treatment and prognosis of patients with NSTEACS according to geographical area,1,7 country2,8, and hospital.9-11
In many hospitals, 2 of the greatest impediments to the correct treatment of patients with acute coronary syndrome are the lack of beds in specialized care units and the lack of cardiologists. Consequently, patients remain in emergency wards and internal medicine departments, which can condition diagnosis and treatment as well as prognosis.11-25 The objective of this study was to analyze the influence of department of initial admission on attention received by patients and prognosis.
PATIENTS AND METHODS
We analyzed data from the PEPA study (Proyecto de Estudio del Pronóstico de la Angina) (Project for the Study of Prognosis in Angina). A total of 18 Spanish centers voluntarily contributed hospital records to this non-randomized, prospective, multicenter study that included all patients with suspected NSTEACS presenting consecutively in emergency wards. All hospitals had a cardiology department and hemodynamic laboratory. Our methods and results have been published elsewhere.6,11 The study included patients presenting with chest pain or discomfort considered by a cardiologist, after initial assessment within 12 hours of admission, as probably due to ischemic heart disease. Patients with persistent ST-segment elevation were excluded as were those transferred from other centers for diagnosis or treatment.
To meet our objectives, patients were classified according to the clinical service to which they were admitted after initial exploration: coronary care unit (CCU), cardiology department (CAR), and internal medicine department (IM). A fourth group consisted of patients who remained in emergency ward (EW) until discharge.
Clinical Data
All clinical definitions were listed in a protocol available to EW clinicians in participating centers. Clinical data of patients were recorded during the first 12 hours after admission using specially designed charts. In each center, final diagnosis was established from information obtained during hospitalization and patients were classified as follows: Q wave AMI (acute myocardial infarction), non-Q wave AMI, unstable angina or non-specific chest pain. A diagnosis of AMI was recorded if creatine kinase (CK) levels were more than twice the normal upper limit, together with an elevation of the MB isoform (CK-MB). Telephone follow-up was carried out at 1 and 3 months when information and current vital status were obtained for 94% of patients. An independent company (Verum Itempharma) conducted quality control and checked data of all patients with an adverse event during follow-up as well as that of a 10% random sample.
Statistical Analysis
Qualitative variables are expressed as number and percentage and quantitative variables as mean ± standard deviation (SD) or median and interquartile interval if data did not follow normal distribution. Baseline patient characteristics and treatments received were compared by chi-square and linear regression analysis for qualitative variables, and ANOVA or Kruskal-Wallis for quantitative variables.
Accumulated incidence of our target variable (mortality or myocardial infarction at 3 months) was calculated from Kaplan-Meier survival curves compared by log rank test. Adjustments for possible confounding factors related to initial department of admission or prognosis were analyzed using a Cox proportional hazards model. We included variables measured on admission which in binary analysis showed a value of P<.10 when compared by initial department of admission and by analysis of 3-month prognosis. This analysis was repeated adjusting for PEPA6 and TIMI5 risk scores. For each group we calculated the adjusted hazard ratio (HR) with a confidence interval (CI) of 95%, taking the HR of CCU inpatients as our reference. Values of P<.05 were considered statistically significant. Data analysis was conducted with SAS statistical software.
RESULTS
We enrolled 4115 patients during the study period: 1086 (26%) were admitted to CCU, 2181 (53%) to CAR, 364 (9%) to IM, and 482 (12%) were discharged from EW.
Clinical Characteristics
Average age was 65±11 years: 33% were women, 26% had diabetes, 33% had a history of myocardial infarction, and 40% had a history of angina.
Baseline characteristics of patients in each group are compared in Tables 1 and 2.
Patients admitted to CCU had a high risk profile and those discharged from EW had a low risk profile. Patients in EW were younger with a higher frequency of women and lower frequencies of diabetes, current cigarette use and history of coronary heart disease. Moreover, presentation with typical coronary heart disease pain, heart failure, or electrocardiographic changes on admission were less frequent among EW patients, none of whom presented CK-MB elevation. In contrast, CCU inpatients had a high risk profile for these characteristics, especially frequency of diabetes (27%), prior myocardial infarction (38%), heart failure (including 2 patients in cardiogenic shock), ST-segment depression (63%), and CK-MB elevation (20%). We compared the seriousness of these characteristics on presentation among the 4 patient groups -- CCU, CAR, IM and EW--and found a statistically significant trend from more serious (CCU) through less serious (EW) (P<.001). These baseline differences were confirmed by calculating PEPA6 and TIMI5 risk scores (Figure 1). Moreover, 20% of CCU inpatients were diagnosed with AMI versus 7% of CAR inpatients, 6% of IM, inpatients, and 0% of EW patients. Final diagnosis of noncardiac chest pain was made for 5%, 19%, 24%, and 24%, respectively (P<.0001).
Fig. 1. PEPA and TIMI risk scores mean (and Standard error) of the 4 groups studied. A progressive reduction in baseline risk profile occurs when comparing patients admitted to coronary care units (CCU) with those in cardiology (CAR), internal medicine (IM), and those discharged from emergency ward (EW); P<.05 for differences between groups.
Treatment
Treatment received and number of diagnostic tests and therapeutic procedures practiced also showed substantial differences according to department of initial admission. Patients in CCU received more intensive treatment and this diminished progressively across the other three groups. This occurred with treatments proven to reduce incidence of death or myocardial infarction in NSTEACS, such as antiplatelet agents (96%, 93%, 91%, and 89%, respectively; P<.0001), heparin (64%, 46%, 27%, and 9%; P<.0001), and beta-blockers (50%, 45%, 27%, and 21%; P<.0001).
We found greater differences on analyzing diagnostic and therapeutic procedures (Figure 2). Exercise tests were used with 34% of patients in CCU, 44% in CAR, 35% in IM, and 12% in EW (P<.0001). Coronary angiography was performed on 46%, 34%, 19%, and 0% of patients respectively (P<.0001), and coronary revascularization on 22%, 12%, 9%, and 0%, respectively (P<.0001). These differences did not parallel patient risk profiles (Figure 1).
Fig. 2. Diagnostic procedures and therapies performed during hospitalization. The greatest differences appear in the performance of coronary angiographies and percutaneous revascularization. Only 12% of emergency ward patients underwent an exercise test prior to discharge. CCU indicates coronary care unit; CAR, cardiology department; IM, internal medicine department; EW, emergency ward.
Clinical Course
Median hospital stay was 10 days (range, 7-16) in CCU, 9 days (range, 6-14) in CAR, 7 days (range, 3-14) in IM, and 0 days (range, 0-1) in EW (P<.0001). In EW, 37% of patients were hospitalized for >24 hours. During hospitalization, incidence of death or myocardial infarction was 8% in CCU, 5% in CAR, 3% in IM, and 0% in EW (P<.0001; Figure 3).
Fig. 3. Incidence of mortality or myocardial infarction on admission (left) and at 3 months (right) of the 4 groups studied. P<.05 for all intergroup comparisons of clinical course at 3 months except coronary care unit (CCU) versus internal medicine (IM) (P=.08) and IM versus cardiology department (CAR) (P=.09) after log rank test.
The number of coronary angiographies performed after discharge was the same in all 4 groups (6%). However, the rate of angioplasties was 6% in CCU, 5% in CAR, 1% in IM, and 2% in EW (P<.0001), whereas the rate of heart surgery was 5%, 5%, 2%, and 1%, respectively (P<.0001). Clinical course at 90 days paralleled risk profiles of CCU inpatients and EW patients, but not those of CAR and IM inpatients. Mortality was 7.5% among CCU inpatients, 3.5% among CAR inpatients, 5.5% among IM inpatients and 2.4% among EW patients (P<.0001) and mortality or AMI rates were 12% and 2% (CCU), 6% and 4% (CAR), 8% and 7% (IM), and 3% and 8% (EW) (P<.0001; Figure 3).
Multivariable analysis conducted after risk-adjustment for differences in profile (age, diabetes, peripheral vascular disease, 2 or more angina crises during 24 hours prior to admission, heart failure on admission, ST-segment depression, and elevated necrotic markers) did not yield significant differences among the 4 groups. Compared with CCU inpatients, hazard ratios (HR) for mortality or myocardial infarction, were: 0.84 (95% CI, 0.68-1.04) among CAR inpatients; 1.24 (95% CI, 0.90-1.66) among IM inpatients; and 0.70 (95% CI, 0.46-1.02) among EW patients. No significant changes appeared when data were adjusted for PEPA or TIMI risk scores.
Although patients with a final diagnosis of noncardiac pain were excluded, differences between those in CCU, CAR and EW were maintained and differences for patients admitted to IM increased. The 90 day mortality or AMI rate was 12.7% among CCU inpatients; 7.4% among CAR inpatients; 11.5% among IM inpatients, and 4.1% among EW patients (P<.00001). Compared to CCU inpatients, these differences were not statistically significant in multivariable analysis. Hazard ratios were 0.87 (95% CI, 0.70-1.09) for CAR inpatients; 1.36 (95% CI, 0.98-1.84) for IM inpatients and 0.72 (95% CI, 0.52-1.02) for EW patients.
DISCUSSION
Our study shows that department of initial admission of patients with NSTEACS conforms adequately to baseline risk profile. However, the department does substantially influence medical management in ways that cannot be fully explained by differences in risk profile, although these differences are not significant to 3-month prognosis.
Incidence of NSTEACS is high and it is the principal cause of admission among patients with ischemic heart disease.1,2 Moreover, the entity is potentially serious, prognosis is uncertain, and adequate infrastructure is needed for correct diagnosis and treatment.3,4 In our study, 25% of patients were admitted to a coronary care unit and 50% to cardiology departments. In contrast, an earlier Spanish study21 found only 40% of patients with a final diagnosis of unstable angina were admitted to CCU or CAR, 42% to IM, and 17% transferred to other centers. This contrasts with data from the Euro Heart Survey of Acute Coronary Syndromes,2 which reports 50% of patients admitted to CCU and 30% to CAR. Our data reflect the lack of beds in CCUs in Spain and explain why these are reserved for high-risk patients.22
Several publications show how clinical approaches to treating patients with NSTEACS vary by geographical area,1,7 country,2,8 and hospital.9-11 We found substantial differences in intrahospital management of patients by department of initial admission. The application of treatments of known efficacy was much more frequent in CAR and CCU than in IM and EW. Consequently, although 72% of IM and EW patients were diagnosed on discharge with unstable angina or myocardial infarction, both pharmacological treatment and clinical course and treatment were clearly less intensive than for CAR and CCU inpatients. Moreover, they did not parallel differences in risk profile and were well below clinical care guideline recommendations.
Some studies of patients with acute coronary syndrome have shown cardiologists follow clinical care guidelines more closely, administer drugs proven to be efficient in randomized clinical trials more frequently, and perform a greater number of diagnostic and therapeutic procedures.12-21,23 In keeping with these differences in treatment, some studies of patients with NSTEACS20,24 show a comparatively better clinical course in patients treated by cardiologists. Schreiber et al20 report 1.8% mortality among patients treated by cardiologists versus 4% among those treated by non-cardiologists; analysis of the American CRUSADE national registry24 shows treatment by cardiologists is associated with a 25% reduction in intrahospital mortality or AMI rates, in comparison with treatment by primary care physicians or internists. However, these results were not adjusted for baseline patient characteristics. In reality, in the global population of patients with acute coronary syndrome these differences in management have not been definitively linked to substantial differences in prognosis even though it has been suggested that patients treated by non-specialist physicians tend to have a worse risk profile and greater comorbidity.18,19,21 The present study contradicts this as CAR or CCU inpatients had a worse risk profile than those admitted to IM and, like patients in the aforementioned studies, they were more frequently administered drugs of proven efficacy, underwent a greater number of clinical care guideline recommended diagnostic procedures and therapies, and showed a non-significant tendency to suffer fewer events during follow-up once data had been adjusted for baseline differences. However, we cannot ignore the fact that the limited number of patients admitted to departments other than cardiology and the short follow-up period may have hidden differences in clinical course.
Overcrowding in emergency wards together with the high incidence of NSTEACS and limited availability of beds for acute patients may lead to missed diagnosis, incorrect early discharge, and outpatient treatment for patients requiring hospitalization. These are recurring problems that have received little attention. In our study, 482 patien ts with suspected NSTEACS were attended and discharged from EW even though 76 % had a final diagnosis of unstable angina and only 12% underwent exercise tests. Although prognosis for these patients was better than for the other groups, as would be expected from their lower risk profile, incidence of mortality or myocardial infarction at 3 months was 4%. Some studies have highlighted the high level of readmission among these patients. Pope et al25 report that 50% of patients diagnosed with unstable angina and discharged from EW were readmitted within the first month. Our results confirm once more that NSTEACS is not limited to the first 24-48 hours evolution but, rather, is of variable duration and can last 1-6 months,1,2,26 requiring intensive hospital treatment with adequate risk stratification on admission and prior to discharge. In this context, chest pain units have proven highly useful in diagnosis, initial risk stratification, and correct application of treatment.27
Limitations of the Study
In this study, centers participated on a voluntary basis rather than being randomized, which limits the interpretation of results. All centers had a cardiology department, CCU and hemodynamic laboratory, so differences reported here might be more marked in centers that do not have this infrastructure. This study took place some years ago and did not consider troponin level measurement on admission, which could influence diagnosis and lead to improved prognostic stratification as well as conditioning the department of initial admission and management of patients. Decisions on discharge or admission in the different departments might be influenced by a multitude of factors in addition to those of a strictly medical nature. Patients who presented complications during the first hours might have been admitted to CAR and CCU, which would make the corresponding results more serious and explain the null incidence of complications in EW during hospitalization. Finally, patients discharged from EW and IM and diagnosed with NSTEACS might have been referred to CAR as outpatients leading to changes in treatment; the number of coronary angiographies performed after discharge was identical in all 4 patient groups suggesting this may well have happened. However, the number of revascularization procedures performed was 3 times fewer among EW and IM patients than among CAR and CCU inpatients.
CONCLUSION
Patients with NSTEACS admitted to CCU or CAR have a higher risk clinical profile than those admitted to IM. They more frequently undergo treatment, diagnostic procedures and therapies of proven efficacy that do not parallel their particular level of risk, although these do not significantly determine clinical course at 3 months. More studies are needed to determine whether these differences persist now that the measurement of troponin levels in patients with chest pain has become widespread, and to identify their long term influence on clinical course differences.
Correspondence: Dr. X. Bosch.
Institut de Malalties Cardiovasculars. Hospital Clínic.
Villarroel, 170. 08036 Barcelona. España.
E-mail: xbosch@medicina.ub.es