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A quantitative analysis of the benefits of pre-hospital infarct angioplasty triage on outcome in patients undergoing primary angioplasty for acute myocardial infarction
Arnoud W.J. van 't Hof1,*,
Henri van de Wetering2,
Nicolette Ernst1,
Frans Hollak2,
Frank de Pooter3,
Harry Suryapranata1,
Jan C.A. Hoorntje1,
Jan-Henk E. Dambrink1,
Marcel Gosselink1,
Felix Zijlstra1,
Menko-Jan de Boer1 on behalf of the On-TIME study group
1Isala Klinieken, Department of Cardiology, Locatie Weezenlanden, Zwolle, The Netherlands
2Ambulance Service Region IJsselvecht, The Netherlands
3Region Noord West Veluwe, The Netherlands
* Corresponding author. Tel: +31 38 4242198; fax: +31 38 4243222. E-mail address: v.r.c.derks{at}isala.nl
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Abstract
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Primary coronary angioplasty has been shown to be a very effective
reperfusion modality in patients with acute myocardial infarction
(MI). However, the time from diagnosis to therapy is often very
long, often due to interhospital transfer of the patient. This
study evaluates the effect of improving logistics by early infarct
diagnosis in the ambulance (ambulance group) and subsequent
transportation to a percutaneous coronary intervention (PCI)
centre without visiting a nearby non-PCI clinic (referred group).
Pre-hospital infarct diagnosis and triage in the ambulance (
n=209)
were compared with triage at a referral non-PCI centre (
n=258)
in patients included in the On-TIME (Ongoing Tirofiban In Myocardial
infarction Evaluation) study. Baseline characteristics of the
two patient groups did not differ significantly, with the exception
of a higher prevalence of males in the ambulance group. The
ambulance group had a significantly shorter time to treatment
(177 vs. 208 min;
P<0.01), a higher initial patency
rate (44 vs. 35%;
P=0.045), a better extent of myocardial reperfusion
(myocardial blush grade 3: 59 vs. 47%;
P=0.02), a trend toward
a higher prevalence of aborted MI (15 vs. 10%;
P=0.08), and
a significantly lower rate of death or re-MI at 1 year of follow-up
(3 vs. 10%;
P=0.004). It was concluded that early, pre-hospital
infarct diagnosis in the ambulance with immediate transportation
to the nearest PCI centre is associated with a shorter time
to treatment and improved angiographic and clinical outcomes
compared with referral from a non-PCI centre in patients who
are candidates to undergo primary angioplasty for acute MI.
Key Words: Acute myocardial infarction • Primary angioplasty • Pre-hospital care • Reperfusion
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Introduction
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Primary coronary angioplasty has been shown to be a very effective
reperfusion modality in patients with acute myocardial infarction
(MI),
1,2 even when additional transport is necessary to a percutaneous
coronary intervention (PCI) centre.
3 The decision that a patient
is a candidate for transportation to a PCI centre, together
with the arrangement of ambulance transport (so called ‘indoor–outdoor’
time), often takes considerable time. In DANAMI 2 (Danish Trial
in Acute MI-2), it took a median of 45 min to decide and
arrange referral to the PCI centre, despite the ideal logistic
in which the presenting ambulance waited for the decision to
transfer.
4 This extra delay might be prevented by pre-hospital
infarct diagnosis and triage, in which patients who are candidates
for primary angioplasty are immediately transported to the PCI
centre.
This study compares pre-hospital infarct diagnosis and triage in the ambulance with triage at a referral non-PCI centre in patients included in the On-TIME (Ongoing Tirofiban In Myocardial Infarction Evaluation) study—a multicentre, placebo-controlled, randomized trial to address the issue of early initiation of tirofiban in patients transferred to undergo primary coronary angioplasty. Forty-one per cent of patients included in On-TIME was randomized in the ambulance after computerized infarct diagnosis.
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Methods
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The design, inclusion criteria, and exclusion criteria of the
On-TIME study have been described previously.
5 In brief, patients
were eligible if they had chest pain for >30 min, together
with >0.2 mV (anterior MI) or 0.1 mV (non-anterior
MI) of ST-elevation in two contiguous echocardiogram (ECG) leads.
Primary angioplasty could be performed within 6 h of the
start of symptoms. Patients aged >80, women aged <50,
patients who were treated with thrombolytic therapy in the previous
24 h, those receiving warfarin or acenocoumarol within
the last 7 days, and those with a contraindication to glycoprotein
(GP) IIb/IIIa blockade were excluded. Patients with severe heart
failure or cardiogenic shock (Killip class III or IV), and patients
who were on haemodialysis were also excluded. The protocol was
approved by each institution's Review Board or Ethical Committee.
Before transportation, oral informed consent was obtained from
all patients by either a physician or a specialized ambulance
nurse. The day after the angioplasty procedure, written informed
consent was requested. Patients were randomized to either early
(before transportation) or late (in the catheterization laboratory)
initiation of tirofiban.
Emergency transportation was performed after pre-information of arrival of the patient at the catheterization laboratory. Enrolling PCI centres were experienced interventional cardiology centres. Recruitment and randomization in the ambulance were initiated only after a period of training in pre-hospital infarct diagnosis and care for at least 6 months. Computer diagnosis in the ambulance was made on the basis of a fixed algorithm, which has been described previously.6,7
Time to diagnosis was defined as the time from symptom onset to infarct diagnosis (first ECG); transportation delay was defined as the time from randomization to arrival at the PCI centre; and total ischaemic time was defined as the time from symptom onset to first balloon inflation.
All angiographic and electrocardiographic parameters were analysed by an independent core laboratory (Diagram Zwolle, The Netherlands) and scored by one observer who was unaware of randomization or outcome data. Cumulative ST-segment deviation was defined as the sum of ST-elevation and depression from all 12 ECG leads, as measured 60 ms after the J-point. ST-segment elevation resolution was calculated as described previously.8
Before transportation, all patients received 500 mg of aspirin and 5000 IU of unfractionated heparin intravenously. Post-PCI, all patients were treated with clopidogrel (300 mg loading dose followed by 75 mg daily for 1 month), aspirin, beta-blockade, statin therapy, and angiotensin-converting enzyme inhibition.
Follow-up was assessed via a planned 30-day visit at the outpatient department and a planned telephonic interview at 1 year. Total death from all causes was recorded. Aborted MI was defined as prolonged chest pain with typical evolutionary ECG changes, coupled with an unstable coronary lesion on the angiogram but without a rise in creatine kinase (CK) of >3 times the upper limit of normal (ULN). Recurrent MI was defined as a new increase in the CK-myocardial bound fraction of more than three times ULN, whether accompanied by chest pain and/or ECG changes, and present in two separate blood samples.
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Statistical analysis
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Statistical analysis was performed with the SPSS 10.0 statistical
package. All non-continuous angiographic variables were analysed
using the
2 test or Fisher's exact test. Continuous variables
were analysed using the analysis of variance or Mann–Whitney
U test (time variables). Risk stratification was based on the
previously described thrombolysis in MI (TIMI) risk criteria.
9 Because of the small number of patients with myocardial blush
grade (MBG) 3 pre-PCI, the combined incidence of MBG 2 and 3
was reported.
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Results
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In the On-TIME study, 40 patients (8%) were randomized at an
emergency room of one of the PCI centres, 258 patients (51%)
were transported from referral hospitals (referred group), and
209 patients (41%) were diagnosed in the ambulance (ambulance
group). The latter two groups form the basis of this report.
Baseline characteristics did not differ significantly between
the groups with the exception of a greater proportion of males
in the ambulance group (
Table 1). Total ischaemic time
was significantly shorter in patients recruited in the ambulance.
The percentage of patients who underwent balloon inflation within
2 h of the onset of symptoms was significantly higher in
patients after triage in the ambulance (
Table 2).
Patients recruited in the ambulance more often had a patent
(TIMI 2 or 3 flow) infarct-related vessel at initial angiography
and a higher rate of coronary bypass grafting as initial reperfusion
modality. Angiographic and clinical outcomes are described in
Table 3. The rate of TIMI 3 flow after PCI did not differ
between the two groups, but the percentage of patients with
MBG 3 was significantly higher in patients recruited in the
ambulance than those in the referred group (59 vs. 47%;
P=0.02).
Aborted MI was present in 15% of the ambulance group and in
10% of the referred group (
P=0.08). The combination of death/recurrent
MI or stroke at 30 days of follow-up occurred in 4.0% of the
referred group, when compared with 2.0% of the ambulance group.
At 1 year of follow-up, death or recurrent MI occurred in 10.4%
of referred patients vs. 3.4% of patients recruited in the ambulance
(
P=0.004).
Table 4 shows the effect of early initiation
of tirofiban in the two different groups. In patients recruited
in the ambulance, a significantly higher initial patency was
found in patients pre-treated with tirofiban. The effect on
thrombus reduction was also most evident in patients who received
tirofiban early in the ambulance.
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Discussion
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This study showed that patients in whom infarct diagnosis and
triage are made in the ambulance and who are immediately transferred
to the PCI centre have a shorter time to treatment and a more
favourable outcome than patients who are triaged and referred
from a non-PCI centre. It shows that further streamlining of
logistics, in which an unnecessary visit to a non-PCI centre
is prevented, saves time and may lead to improved patient outcome.
The results show that, in particular, presentation delay is shorter in patients who are diagnosed in the ambulance. Of the ambulance patients, 23% underwent angioplasty within 2 h of the onset of symptoms compared with only 7% of patients who were referred from other centres (P<0.001). In addition, the ambulance group showed a higher initial patency. This shorter time to treatment, together with a higher initial recanalization rate, is probably the reason for the higher number of patients with an aborted MI in the ambulance group.
Initial patency
The finding that patients diagnosed and triaged in the ambulance have a higher initial patency than those transferred from a non-PCI centre was also reported in a previous study.7 The very early administration of aspirin and heparin might be the reason for the higher recanalization rate in these patients. From Table 4, it is also clear that the early administration of tirofiban is more effective in patients recruited in the ambulance, possibly because the occlusive thrombus is less organized when the patient is treated early after the onset of symptoms. In thrombolytic trials, the concept of increased effectivity with shorter duration of symptoms is well recognized and is known as the ‘golden hour’; this concept might explain the better outcome seen in patients treated with pre-hospital thrombolysis than in those given thrombolysis in hospital.10
Myocardial reperfusion
With regard to epicardial reperfusion, no difference in post-PCI TIMI 3 flow was seen between the two groups. However, the rate of normalized myocardial blush (MBG 3) was significantly higher in the ambulance group than in the referred group, suggesting that, in particular, myocardial reperfusion was better in this group of patients. This is probably due to the shorter time to treatment in this group, as previous studies have shown that ischaemic time is an independent predictor of the extent of myocardial reperfusion.11,12
Clinical implications
The most recent version of the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the treatment of patients with ST-elevation acute MI (STEMI) state that a pre-hospital 12-lead ECG should be made by Advanced Cardiac Life Support providers in all patients suspected of STEMI (class IIa, level of evidence B) and that all patients with a high risk of dying should immediately be transferred to the PCI centre (class IIa, level of evidence B).13 The study reported here shows that the implementation of these guidelines might further improve outcome, merely by reducing time to treatment, especially in those patients at high risk of adverse events. These high-risk patients, in particular, might benefit from a further reduction in time to treatment.14
Limitations
This study is not a randomized comparison between triage in the ambulance and triage at a referral centre. It would no longer be ethical to conduct such a trial as this would mean that treatment delay would deliberately be increased in one arm. In the ambulance group, total ischaemic time was significantly shorter than in the referred group, but the shorter transportation time in this group could have been a contributory factor. Referred patients travelled a median of 41 km to the PCI centre, whereas ambulance patients were transported a median of 24 km. It is difficult to differentiate which part of this reduced transportation distance is due to improved logistics and which is due to a possible shorter distance to the PCI centre.
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Conclusions
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In patients who are candidates for primary angioplasty for acute
MI, pre-hospital infarct diagnosis and triage is associated
with shorter time to treatment, a higher initial patency, and
better angiographic and clinical outcomes after PCI compared
with triage and referral from a non-PCI centre. All efforts
should, therefore, be made to implement pre-hospital infarct
diagnosis, triage, and therapy in the care of patients with
an acute MI.
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Acknowledgement
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This study was supported by an unrestricted grant from Merck
& Co., USA. We wish to thank all ambulance personnel for
their contribution to this study.
Conflict of interest: The On-TIME trial was supported by an unrestricted grant from Merck & Co., USA. Dr van 't Hof has received speaker fees for various presentations about the results of the trial.
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Appendix I
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Members of the On-TIME study group
Steering Committee: M.J. de Boer, E. Boersma, A.J. van Boven,
R. Buirma (non-voting member), J. Dille, A.W.J. van't Hof, R.J.
de Winter.
Ambulance Coordinators: F. Hollak (Ambulance Dienst
Regio IJssel Vecht), F. de Pooter (Ambulance Dienst Regio Noord
West Veluwe).
Referral Centre Coordinators: T. Bouwmeester (Winschoten),
R. Brons (Meppel), R. Dijkgraaf (Harderwijk), W. Jap (Apeldoorn),
M.J. de Leeuw (Assen), A. Mosterd (Amersfoort), C. Oei (Heerenveen),
J. Saelman (Hoogeveen).
PCI Centre Coordinators: The Netherlands:
J.M. ten Berg (Nieuwegein), A.J. van Boven (Groningen), J.H.E.
Dambrink (Zwolle), R.J. de Winter (Amsterdam); Italy: S. Petronio
(Pisa).
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References
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Abstract
Introduction