Impact of pre-hospital care in patients with acute myocardial infarction compared with those first managed in-hospital
T.P. Mathew,
I.B.A. Menown,
D. McCarty,
H. Gracey,
L. Hill and
A.A.J. Adgey*
Regional Medical Cardiology Centre, Royal Victoria Hospital, Belfast, Northern Ireland, UK
Received July 15, 2002;
accepted July 17, 2002
* Correspondence: Professor A. A. J. Adgey, Regional Medical Cardiology Centre, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland, U.K.
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Abstract
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Aims To compare prospectively the impact of pre-hospital care by a physician-staffed mobile coronary care unit with patients managed initially in-hospital, all with acute myocardial infarction.
Methods and results This was a single centre registry of consecutive patients (n=750) admitted with acute myocardial infarction to the coronary care unit and cardiology wards of the Royal Victoria Hospital, Belfast between 1998 and 2001. For the 750 patients, in-hospital mortality was 11% and was significantly lower for those managed pre-hospital (8% vs 13%, P=0.04): patients who received fibrinolytic therapy (n=474), the in-hospital mortality was significantly lower in the pre-hospital group (7% vs 13%, P=0.02). Those managed pre-hospital had significant reduction in the median delay times (25th, 75th percentiles) from onset of symptoms to call for help 1.0 (0.5, 2.2) vs 2.0 (0.9, 6.0) h, P<0.001, from call for help to receiving fibrinolytic therapy 1.0 (0.8, 1.5) vs 1.8 (1.2, 2.5) h, P<0.001 resulting in a shorter pain-to-needle time for fibrinolytic therapy 2.3 (1.5, 3.8) vs 4.0 (2.6, 7.2) h, P<0.001. For all patients, older age, haemodynamic indicators on admission (hypotension, higher heart rate, heart failure) and managed by the in-hospital route were significant independent variables for an adverse in-hospital mortality. Although for patients aged
75 years no statistical significant reduction in mortality occurred for those managed pre-hospital (P=0.051), nevertheless patients in this age group first treated pre-hospital who received fibrinolytic therapy had a significantly lower mortality than those first treated in-hospital (21% vs 43%, P=0.02).
Conclusions Consecutive patients with acute myocardial infarction seen and managed initially out-of-hospital by a physician-staffed mobile coronary care unit had significantly lower in-hospital mortality.
Key Words: Myocardial infarction pre-hospital care mortality fibrinolytic therapy
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Introduction
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The prompt delivery of high quality coronary care to patients following acute coronary syndromes is of paramount importance. This is especially so in acute myocardial infarction (AMI) with ST elevation on the presenting electrocardiogram, where the rapid restoration of patency of the infarct related artery improves survival.1 Early fibrinolytic therapy for many years has been the gold standard, with studies consistently showing reduced mortalityfollowing appropriate administration of these agents.2,3 However timing of treatment is of the essence with the greatest benefit in those patients in whom the pain-to-needle time is short.25
Delay in initiating treatment after AMI may be categorized into two phases: patient delay, i.e. the time between symptom onset and call for help and healthcare system delay which encompasses the response to patient call, transport to the institution, and the time to appropriate treatment following arrival at hospital. Over the years various methods have been proposed to reduce thesedelays.6 Provision of out-of-hospital mobile coronary care in the community with staff trained in the recognition and management of acute myocardial ischaemia/infarction reduces transport and hospital delay times. The efficacy and safety of such pre-hospital initiated treatment has been demonstrated in many early studies.7,8
Patients with ST segment elevation on the initial ECG and suitable for fibrinolytic therapy have been studied out-of-hospital.6,915 A small number of randomized trials have also compared the efficacy of pre-hospital initiated fibrinolytic therapy with therapy first commenced in-hospital.6,9,10,1214,16 These studies have demonstrated consistently a reduced pain to needle time with pre-hospital treatment, with an average gain of 1 hr.17,18
A physician-staffed pre-hospital coronary care unit in addition to providing early fibrinolytic therapy has the advantage of prompt identification and treatment of the early complications of acute myocardial ischaemia/infarction. We therefore compared prospectively the in-hospital mortality associated with pre-hospital coronary care where patients were initially managed out-of-hospital by a 24 h physician-manned mobile coronary care unit with those presenting in-hospital and managedinitially by the Emergency Department, otherhospital wards/departments e.g. Chest Pain Clinic before transfer to the hospital coronary care unit. All patients had a discharge diagnosis of AMI.
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Methods
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Consecutive patients admitted with chest pain to the coronary care unit and cardiology wards of the Royal Victoria Hospital between February 1998 and March 2001 and who had an ultimate diagnosis of AMI were reviewed. Patients transferred from other hospitals after AMI for further investigations were excluded. The Royal Victoria Hospital serves a population of approximately 600 000 people. A 24-h mobile coronary care unit (MCCU) has been operational from this hospital since 1966. A junior doctor and a coronary care nurse staff the MCCU. The ambulance is equipped with a defibrillator which can also record the 12-lead ECGs. In addition there are facilities for transmitting ECGs digitally to the ward. Requests for attendance by MCCU can come directly from a member of the public, from a family Practitioner or an attending ambulance crew or via the ambulance control from a 999 (emergency) call. The median response time of the MCCU has been shown to be 10 min.19
Data were collected prospectively and entered into a database (Microsoft Access) by a research nurse. Patients were followed until hospital discharge. The diagnosis of AMI was based on a suggestive history of rest ischaemic chest pain with serial ECG changes (ST elevation, ST depression, T wave inversion or left bundle branch block) or elevated cardiac markers (CK-MB>2x upper limit of normal or cTnI
1.0 µg.l1(Dade and Behring and Johnson and Johnson)). Patients were deemed eligible for fibrinolytic therapy up to 12 h from onset of symptoms. Contraindications included hypertension, prior haemorrhagic stroke, recent major surgery/trauma, prolonged cardiopulmonary resuscitation, active bleeding, oral anticoagulation or haemorrhagic diathesis. Age was not a contraindication to fibrinolytic therapy. Killip class was defined as: class I-absent rales and S3, class II-rales <50% lung fields, class III-rales >50% lung fields, class IV-shock.
Invasive investigations and interventional treatment were at the discretion of the consultantcardiologist. As the unit participates in many international multicentre fibrinolytic trials, varyingfibrinolytic regimens were used during the study period. However these were administered equally to patients admitted by the MCCU or from other sites.
Statistical analysis
Continuous variables were expressed as mean (±SD) or median (25th and 75th percentiles). Continuous variables were tested by an independent samples t-test or Mann-Whitney U test as appropriate. The P values for comparison of categorical variables were determined by the Pearson chi-square test for proportions with appropriate degrees of freedom. P<0.05 was taken as significant. Multivariate analysis used forward stepwise (likelihood ratio) logistic regression. All calculations were carried out with SPSS 10.0 software package.
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Results
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Of the seven hundred and fifty patients, there were 510 (68%) men and 240 (32%) women with a mean age of 65±12.6 years (range 26104) (Table 1). One hundred and ten (15%) of patients were
50 years, 465 (62%) aged 51 to 74 years and 175 (23%) were
75 years. ST elevation on the admission ECG was present in 578 (77%) patients. Of the remaining 172, ST segment depression occurred in 72, T inversion in 58 and normal, bundle branch block or paced rhythm in 42. The ultimate electrocardiographic site of infarction was determined as anterior in 272 (36%), inferior in 354 (47%), lateral in 56 (8%) and indeterminate in 68 (9%) patients. The mediandelay time from onset of symptoms to call for help was 1.5 (0.62, 4.0) h.
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Table 1 Baseline, clinical characteristics, angiography and intervention in patients according to source of admission
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Three hundred and twenty six (43%) patients were first treated pre-hospital (PH) by theMCCU and the rest treated first in-hospital (IH) i.e. Emergency Department (259) or other hospital wards/departments (165) e.g. Chest Pain Clinic, Outpatient Clinic, Treadmill Room or directly from GPs (Fig. 1). PH and IH patients were comparable with regard to history of hypertension (32% vs 32%), current smokers (40% vs 38%), anterior MIs (37% vs 36%), Killip class II and III (Killip II rales <50% lung fields and Killip class III rales >50% lung fields) 27% vs 29%, admission heart rales (77±24 vs 79±18, (n=746)) and hypotension on admission (defined as systolic blood pressure (SBP)
80 mmHg) 8% vs 5% (n=749) (Table 1). Cholesterol or knowledge of prior statin therapy was available in 712 of the750 patients with a similar incidence for PH andIH patients (68% vs 68%). For family history of ischaemic heart disease (n=739) pre-hospital vs in-hospital groups was 63% vs 57%, P=0.07. Pre-hospital patients compared with IH patients were younger (64±12 vs 66±13, P=0.05), more likelyto be male (73% vs 64%, P=0.01), had a shorter median delay time from symptom onset to call for help 1.0 (0.5, 2.2) vs 2.0 (0.9, 6.0) h, P<0.001 (n=720), were more likely to have ST elevationon the admission ECG (85% vs 71%, P<0.001), and history of ischaemic heart disease (angina, MI or revascularization; 39% vs 28%, P=0.001) or previous MI only (34% vs 23%, P<0.001), but less likelyto have diabetes mellitus (12% vs 19% P=0.01) (Table 1).

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Figure 1 Percentage of patients according to source of admission. MCCU=mobile coronary care unit (pre-hospital group); A&E=accident and emergency; Ward Tr=transfer from other wards; Others=patients admitted from other sources (chest pain clinic, outpatient clinic, treadmill room or directly by the GP).
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Fibrinolytic therapy was administered to 474 (63%) patients. Pre-hospital patients compared with IH patients received fibrinolytic therapy more frequently (79% vs 51%, P<0.001). In these patients, the baseline characteristics were comparablebetween the PH and IH groups except for anincreased incidence of previous ischaemic heart disease and a trend for more males in the PH group (Table 1). The median delay time from onset of symptoms to call for help was 1.0 (0.5, 2.0) for the PH group and 1.9 (0.9, 4.3) h for the IH group, P=<0.001 (n=467). There was a significant reduction in the median delay time from call for help to receiving fibrinolytic therapy 1.0 (0.8, 1.5) vs 1.8 (1.2, 2.5) h, P<0.001 in the PH group resulting in a shorter pain-to-needle time (time from symptom onset to administration of fibrinolytic therapy) 2.3 (1.5, 3.8) vs 4.0 (2.6, 7.2) h, P<0.001 compared to the IH group. Thus there was a saving of 1.7 h (median) in the administration of fibrinolytic therapy from symptom onset for the PH groupcompared to the IH patients.
Analysis of those with ST elevation (n=578) showed similar results to those receiving fibrinolytic therapy (Table 1). The differences in age, sex, diabetes, systolic BP
80 mmHg reached statistical significance when analysed by ST elevation.
Sixty six percent of patients seen by the MCCU received fibrinolytic therapy within 3 h of symptom onset, whereas only 30% of patients admitted to hospital were treated within the same time (Fig. 2). Coronary angiograms and percutaneous coronary interventions (PCI) were carried out more commonly in the PH group during the hospital stay (60% vs 48% and 36% vs 25%, P=0.001) (Table 1). This was also so for those who received fibrinolytic therapy (63% vs 49%, P=0.002 and 38% vs 26%, P=0.007) (Table 1).
In-hospital mortality for the 750 patients was 11% (n=82) and was significantly lower for the PH compared to IH group (27/326: 8% vs 55/424: 13%, P=0.04) (Fig. 3, Table 2). Similarly for patients who received fibrinolytic therapy, the in-hospital mortality was significantly lower in the PHgroup (17/257: 7% vs 28/217: 13%, P=0.02) (Fig. 3, Table 2).
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Table 2 Univariate predictors and risk estimates (odds ratio (OR) with 95% confidence interval) of in-hospital mortality for categorical variables
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The mean age of patients who died in-hospital was significantly higher compared to patients who survived (76±9.1 vs 63±12.2 years, P<0.001). The univariate predictors and risk estimates of categorical variables for in-hospital mortality are shown in table 2. For the total patients, comparing those who died with those who survived, age
75 years, female gender, non-smoking status, anterior MI, and indicators of haemodynamic disturbance (higher admission heart rate, Killip class II&III and hypotension (SBP
80 mmHg)) were significant univariate predictors of in-hospital mortality (Tables 2 and 3). Admission type was also a significant univariate predictor of mortality, i.e. patients admitted by the MCCU had a lower risk of dying than patients admitted through other routes (8% vs 13%, P=0.04) (Table 2).
For the patients who received fibrinolytic therapy (n=474), age
75, female gender, non-smoking status, non-ST elevation AMI, haemodynamic indicators (admission heart rate, Killip class II & III and hypotension), initial admission first in-hospital and longer delay time (call to fibrinolytic therapy) were significant univariate predictors of in-hospital mortality (Tables 2 and 3).
All significant univariate predictors (P<0.05) were included in a multiple logistic regression model to examine their independent influence on mortality after adjusting for other variables. For all patients, older age (OR 8.5, 95% CI 4.914.7, P<0.001), haemodynamic indicators on admission (hypotension: OR 11.5, 95% CI 5.026.1, P<0.001, higher heart rate: OR 1.02, 95% CI 1.011.03, P=0.001, heart failure: OR 1.8, 95% CI 1.023.0, P=0.04) and site of first treatment (in-hospital: OR 1.9, 95% CI 1.043.3, P=0.04) were significant independent variables for an adverse in-hospital mortality. For those patients who received fibrinolytic therapy, older age (OR 13.6, 95% CI 6.030.6, P<0.001), haemodynamic indicators on admission (hypotension: OR 12.5, 95% CI 3.939.6, P<0.001, higher heart rate: OR 1.03, 95% CI 1.011.04, P=0.001, heart failure: OR 2.3, 95% CI 1.15.1, P=0.04), delay from call for help to administration of fibrinolytic therapy (OR 1.1, 95% CI 1.0041.2, P=0.04) and managed by in-hospital route (OR 2.4, 95% CI 1.15.4, P=0.04) were significant forin-hospital mortality adjusting for other variables.
To adjust for the significant differences noted in the baseline characteristics (Table 1) between the two groups, we performed a further regression analysis including these variables (age, gender, smoking status, admission type, presence orabsence of ST elevation on admission ECG, diabetes and previous history of IHD, haemodynamic indicators on admission such as heart rate, systolic blood pressure and heart failure, delay factors: call to fibrinolytic therapy and onset to fibrinolytic therapy and whether PCI was performed or not). Admission by in-hospital route was still an independent predictor of mortality for all patients (n=750) (OR 1.8, 95% CI 0.9973.3, P=0.051, P out=0.046) and for those 474 patients whoreceived fibrinolytic therapy, in hospital OR 2.4, 95% CI 1.15.5, P=0.04.
Patients
75 years
Among the 750 patients, 175 (23%) were
75 years. In-hospital mortality was 31%. There was an absolute risk reduction of 14% in mortality for patients first seen and managed by the MCCU in comparison to those first managed in-hospital (OR for PH 0.497, 95% CI 0.21.01, P=0.051). There was no significant difference in mortality in patients whoreceived fibrinolytic therapy (n=99) compared to those who did not receive fibrinolytic therapy (n=76; 32% vs 29%, P=0.63) (Table 4). In those with ST elevation on admission ECG (n=135), again there was no difference in the in-hospital deaths in those who received fibrinolytic therapy compared to those who did not receive fibrinolytic therapy (33% vs 33%, P=0.9). The average admission heart rate for those who died was 86±27.9 and for those who survived 79±19.5, P=0.046. Multivariateregression analysis in this group (n=175) identified hypotension on admission (OR 22.8, 95% CI 4.8108.9, P<0.001), admission heart rate (OR 1.02, 95% CI 1.01.03, P=0.05) and anterior MI (OR 2.3, 95% CI 1.14.7, P=0.02) as significant independent variables for higher mortality for all patients. For the group who received fibrinolytic therapy (n=99), hypotension on admission (OR 10.0, 95%CI 1.855, P=0.008) and admission type (IH: OR 3.2, 95% CI 1.28.4, P=0.02) were significant for mortality adjusting for other variables.
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Table 4 Univariate predictors and risk estimates (odds ratio (OR) with 95% confidence interval) of in-hospital mortality for categorical variables in patients 75 years
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Discussion
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Pre-hospital care for AMI was first introduced in the 1960s to manage the early complications of AMI, in particular ventricular fibrillation.7,8 In the fibrinolytic era, trials have consistently demonstrated the benefit of early therapy.2,3,20 In GISSI I, if fibrinolytic therapy was given within 1 h of symptom onset, the mortality was approximately half compared with a mortality reduction of approximately one fifth if therapy was delayed to between 3 and6h from pain onset.2 However conventional care patterns appear to result in marked delay to therapy.20 In 1997 only 14.5% of patients in the U.K. received fibrinolytic therapy within 60 min of the call for help.21
In the early 1980s the 12-lead ECG guided administration of fibrinolytic therapy commenced in our pre-hospital MCCU with the aim of reducing onset of symptoms to fibrinolytic therapy. The findings from this and other studies show that use of pre-hospital care does reduce the call-to-needle time.17 In the European Myocardial Infarction Project (EMIP), a multicentre double-blind study, patients seen within 6 h of the onset of symptoms and a qualifying 12-lead ECG were randomlyassigned to receive either anistreplase beforeadmission, followed by placebo in the hospital(pre-hospital group, n=2750), or placebo before admission, followed by anistreplase in the hospital (hospital group, n=2719).9 Those in the pre-hospital group received fibrinolytic therapy amedian of 55 min earlier than those in the hospital group. In the GREAT study, a randomized double-blind parallel-group trial, 311 patients with suspected AMI were seen by their general practitioners within 4 h of symptom onset and were given intravenous anistreplase (30 U) either at home or later, after arrival in the hospital.13 Home and hospital administration times were 101 and 240min(median) respectively, after symptom onset. The median time saved by pre-hospital administration was 130 min.22 In the Myocardial Infarction Triage and Intervention (MITI) Trial, 360 patients with AMI and symptoms for 6 h or less were randomized to pre-hospital-initiated vs hospital-initiated fibrinolytic therapy.16 Initiating treatment before hospital arrival decreased the interval from symptom onset to treatment from 110 to 77 min (P<0.001).16
In this study, we found patients receiving pre-hospital care had a lower in-hospital mortality compared to those first seen and managed in the hospital (8% vs 13%, P=0.04). For those receiving fibrinolytic therapy, pre-hospital administration compared to in-hospital administration was associated with a lower in-hospital mortality (7% vs 13%, P=0.02). Similarly in the GREAT study, 3 month mortality was 8% for the 163 patients givenanistreplase at home compared with 15.5% for the 148 patients who received anistreplase in the hospital (P=0.04).13 However the findings of other studies is less clear. In the EMIP trial, while death from cardiac causes at 30 days was significantly less frequent in the pre-hospital group than in the hospital group (8.3% vs 9.8%; reduction in risk, 16%; 95% CI 029%; P=0.049), there was only a trend to a reduction in overall mortality at 30 days in the pre-hospital group (9.7% vs 11.1% in the hospital group; reduction in risk, 13%; 95% CI 1 to 26%; P=0.08).9 In the MITI trial, pre-hospital compared with in-hospital treatment only showed a non-significant trend to reduction in mortality (5.7% vs 8.1%).16 However the overall reduction in symptom onset to needle time was more modest (33 min), and treatment given within 70 min of symptom onset compared with later treatment was associated with a reduction in mortality (1.2% vs 8.7%; P=0.04).16
A key aspect of our study is the incorporationof real world practice. In previous randomizedstudies, patients randomized at pre-hospitalpresentation to in-hospital treatment were brought to hospital by the same ambulance, with thesame staff, and given treatment very early onarrival.6,9,10,13,14,16 Hence the hospital delay time was negligible. However in routine clinical practice, patients not receiving pre-hospital care (or in hospitals without a MCCU) are usually admitted to the coronary care unit from the emergency department or from a medical observation ward with the associated inherent delays. This may also explain why many of the previous pre-hospital studies with the notable exception of the GREAT trial, did not individually show a significant reduction in mortality,6,9,14,16 The time saving in these trialsbecause of the artificial reduction in hospital delay may have masked the benefit of pre hospital initiation of therapy. The time saving achieved in the GREAT trial is the longest (130 min) of all the previous randomized pre-hospital fibrinolytic trials and is probably because hospital personnel were not involved in pre-hospital care.22 Our study looked at the benefit of MCCU pre-hospital care by a physician-staffed unit rather than a paramedic or other personnel. It is possible that initial ECG evaluation by non-cardiologists may result in failure to recognize minor or subtle ECG abnormalities and thus a delay in treatment.
The finding of lower mortality in the pre-hospital group in this study is likely to be multifactorial.All delay timings were significantly less in thepre-hospital group with call to needle time an independent variable associated with adversein-hospital mortality. Patients admitted via the MCCU were more likely to receive fibrinolytic therapy (79% vs 51%, P<0.001). The presence of a physician at the pre-hospital presentation may also enable the earlier identification and appropriate management of AMI complications and thus pre-hospital care was an independent predictor ofsurvival. Our mortality evaluation was limited to in-hospital duration. However findings from the GREAT study suggest that a mortality reduction may still be seen at 1 year.22
Age was the most significant univariate and multivariate variable associated with in-hospital mortality in this study. Patients
75 years had 68 times higher risk of death compared to those aged less than 75 (Table 2). Whilst concerns have beenexpressed from observational data that fibrinolytic therapy increases mortality in the elderly with AMI,23 nevertheless in this study pre-hospital care independently reduced the in-hospital mortality in this high risk group who received fibrinolytic therapy, and in addition there was a strong trend (P=0.051) to reduction in in-hospital mortality for the total group (Table 4). Although there was no significant difference in mortality between those patients who received fibrinolytic therapy from those who did not, nevertheless in those whoreceived fibrinolytic therapy pre-hospital the benefit of PH administration would also include prompt and appropriate management of early complications of AMI by trained staff. The importance ofage has also been seen in this study where there was a higher in-hospital mortality for femalepatients and non-smokers: smokers tend to first present with ischaemic heart disease at a younger age (Table 2).24,25
In summary, our study has confirmed that a 24 h physician-staffed MCCU provides pre-hospitalassessment and early administration of fibrinolytic therapy. It has been shown that patients receiving pre-hospital care have a lower in-hospital mortality which is independent of other variables. It also results in a significant reduction in call to needle time for those receiving fibrinolytic therapy. If targets for early administration of fibrinolytic therapy are to be met, methods to enable pre-hospital administration of fibrinolytic therapy by paramedic, nursing or medical personnel are likely to be required.
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Acknowledgments
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Our grateful thanks to Boehringer Ingelheim for a grant to run the AMI Registry, to Dr Gordon W, Cran (Department of Epidemiology and public health, Queens University of Belfast) for advise on statistical analysis and to Mary O'Neill for secretarialassistance.
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