Patient Transfer
Mark de Belder
The James Cook University Hospital
Middlesbrough
Current Management Strategies for ACS
ACS
No ST Elevation
Early
Invasive
Early
Conservative
ST
STElevation
Elevation
PRIMARY
Fibrinolysis
Primary
Fibrinolysis
Primary
Fibrinolysis
PCI
PCI
PCI
Guidelines for the management of non-STEMI
Acute Coronary Syndromes
Coping with ACS angiography
• Rapid turnover of patients required (pressure on ambulance
services)
• Organisation of diagnostic and revascularisation services
• Cath lab spaces required every day in interventional centres
• Referral to a specific cath lab slot rather than a specific Consultant
• Increased use of Cath ? Proceed slots (for elective work as well)
• Referring hospitals need to take some patients back after
revascularisation (?swaps)
• Weekend working?
• Elective work may have to slow pending an increase in the
infrastructure for angiography
• Clinical networks with appropriate support from commissioners
Patient Transfer
in the setting of
STEMI
Meta-analysis of 23 randomised trials
7739 patients: 4-6 week data
Keeley EC, Boura JA, Grines CL
The Lancet 2003;361:13-20
P=0.0002
P=0.0003
P<0.0001
P=0.0004
P<0.0001
14%
12%
10%
8%
PCI
Lysis
6%
4%
2%
0%
Death
Exc.Shock
Non-fatal MI
CVA
Combined
Meta-analysis of 8 randomised trials
Streptokinase trials - 1837 patients
Keeley EC, Boura JA, Grines CL
The Lancet 2003;361:13-20
0.53 (0.37-0.75)
0.11 (0.05-0.26)
0.32 (0.09-1.21)
0.40 (0.28-0.58)
18%
16%
14%
12%
10%
PCI
Lysis
8%
6%
4%
2%
0%
Death
Non-fatal MI
CVA
Combined
Meta-analysis of 15 randomised trials
Fibrin-specific trials - 5902 patients
Keeley EC, Boura JA, Grines CL
The Lancet 2003;361:13-20
0.80 (0.66-0.96)
0.42 (0.31-0.55
0.49 (0.31-0.77)
0.57 (0.48-0.69)
14%
12%
10%
8%
PCI
Lysis
6%
4%
2%
0%
Death
Non-fatal MI
CVA
Combined
Meta-analysis of 5 randomised trials
Transfer for PCI vs On-Site Lysis
2909 patients: 4-6 week data
Keeley EC, Boura JA, Grines CL
The Lancet 2003;361:13-20
P=0.057
P<0.0001
P=0.049
P<0.0001
16%
14%
12%
10%
PCI
Lysis
8%
6%
4%
2%
0%
Death
Non-fatal MI
CVA
Combined
Mortality by time to presentation
14%
12%
10%
8%
PCI
Lysis
6%
4%
2%
0%
<2 hrs
2-4hrs
>4hrs
Ziljstra EHJ 2002;23:556
30-day mortality by time from enrollment
to first balloon inflation
16%
14%
12%
10%
8%
PCI
6%
4%
2%
0%
<60mins 61-75mins 76-90mins >91mins No PTCA
Berger P et al, Circ 1999;100:14-20 (GUSTO-IIb)
Door-to-Balloon times in Primary PCI
outside of trials
N=27,080
Cannon CP, Gibson CM, et al. JAMA 2000
P=NS
1.8
P=NS
P=0.01
1.62
1.6
P=0.0003
1.61
1.41
1.4
1.14
1.15
0-60
61-90
91-120
121-150
151-180
>180
N=2,230
N=5734
N=6616
N=4461
N=2627
N=5412
1.2
1
P=0.0007
1
0.8
0.6
0.4
0.2
0
Corrected for age, anterior MI location & gender
CAPTIM
Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction
Bonnefoy E et al, The Lancet 2002;360:825-29
A trial of prehospital fibrinolysis plus selected PCI
840 randomised
419
pre-hospital
alteplase
5 primary PCI
14 no lysis
421
primary
PCI
16 had no angiography
41 no PCI
400
pre-hospital
alteplase
134 (33%)
unscheduled Urgent PCI
295 (70%)
unscheduled PCI within 30 days
364
primary PCI
16 (4%)
unscheduled urgent PCI
60 (14%)
unscheduled PCI within 30 days
CAPTIM
Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction
Bonnefoy E et al, The Lancet 2002;360:825-29
Physician-manned mobile emergency-care units
(Service d’Aide Medicale d’Urgence – SAMU)
Planned for 1200 patients
Trial terminated early due to lack of funding
30 day
Composite
Death
Reinfarction
Death &
recurrent
ischaemia
Disabling Stroke
Pre-hospital
lysis n=419
34 (8.2%)
Primary PCI
n=421
26 (6.2%)
P value
16 (3.8%)
15 (3.7%)
57 (13.5%)
20 (4.8%)
7 (1.7%)
41 (9.8%)
0.61
0.13
0.06
4 (1%)
0
0.12
0.29
Pre-hospital lysis - ER-TIMI19
Morrow DA et al, JACC 2002;40:71-7
315 pts (65 cath’d) vs 650 in-hospital lysis pts
Pre-hosp
rPA
EMS
Arrival
0
90mins post-lysis
49%
>70% STres
13%
>70% STres
ED
Arrival
4.7% death
3.3% reMI
30
60
90
120
1% ICH
In-hospital
65
(21%)
cath’d
lysis
56 (18%) PCI
mins
150
90mins post-lysis
48%
>70% STres
33%
>70% STres
EMS
Arrival
0
30
60
90
120
150
mins
Why so little primary PCI in UK?
• Lack of evidence?
• Belief in pre-hospital lysis?
• Insufficient PCI centres?
• Too few cardiologists?
• (Interventional) cardiologists have too many other
things to do?
• Reluctance to take on nocturnal work?
• Competing demands for finances (statins, ACE-I,
DES, ICDs etc)?
• Lack of organisation?
Transferring patients for Primary PCI
Zijlstra F et al, Heart 1997;78:333-6
The Weezenlanden Hospital, Zwolle
Symptom-onset to
admission
Local admission to
WZL admission
WZL door-to-balloon
time
Total ischaemia time
Local patients
Transferred
N=416
129 (69) mins
N=104
90 (60) mins
-
70 (27) mins
67 (28) mins
39 (31) mins
196 (74) mins
200 (62) mins
Transfer patients (104)
10 in shock (1 died)
1 ventilated prior to transfer
1 intubated during transfer
1 VT – lignocaine
2 VF – defibrillated
2 required IV fluids
Helicopter vs Ambulance transfer for
Primary PCI
Straumann E et al, Heart 1999;82:415-9
Triemli Hospital, Zurich
Ambulance
N=54
8 (5-68)
Distance
(km)
Journey time 47 (15-126)
(mins)
Total transfer 50 (18-110)
time (mins)
Helicopter
N=14
42 (24-122)
Total
N=68
9 (5-122)
Sig
55 (18-115)
0.02
0.0001
37 (7-60)
63 (40-115)
3 patients died in shock prior to transfer
0 patients transferred died
8 patients were ventilated during transfer
0 defibrillation during transfer (15 resuscitated prior to transfer)
AIR PAMI
138 patients: 30 day data (trial stopped for poor recruitment)
Grines CL et al, JACC 2002;39:1713-9
P=0.46
P=1.0
P=0.11
P=0.33
P=0.007
35%
30%
25%
20%
PCI
Lysis
15%
10%
5%
0%
Death
Non-fatal
reMI
CVA
MACE
Ischaemia
79% ambulance transfer 26±28 miles; 21% Helicopter 57±50 miles
0 patients needed resuscitation during transfer, 0 patients died
ER to treatment times 174±80 for transfer vs 63±39 mins for local lysis
DANAMI-2
• 22 referring hospitals
• 5 PCI centres
• Serving two thirds of the Danish population
(5.4million)
• Plan for 1100 patients at referring hospitals and 800
patients at invasive centres
• Average distance 35 miles (56km)
• Up to 95 miles (153km)
• Halted by Safety & Efficacy Committee after 1129
patients enrolled because of clear efficacy in PCI
patients
DANAMI-2 Trial design
ST-elevation MI < 12 hours
Randomization (total planned 1900 pts)
* Referral Hospital: Planned 1100 pts at 24 sites
* Angioplasty Center: Planned 800 pts at 5 sites
Fibrinolysis
Accelerated tPA
(max. 100 mg)
Stent
Acute transfer for
1° PTCA + stent
Primary Endpoint:
Death, Reinfarction, or Disabling Stroke through
30 days
Anderson HR et al, ACC 2002; Oral Presentation
Lysis
DANAMI-2 - Time from Symptom Onset
to Admission and Time from Door to Rx
Hospital
Referral
Symptom to Hosp.
Invasive
Symptom to Hosp.
Door to t-PA
Door to t-PA
1° PCI
Average Door to Balloon
(jncludestransfer) < 120 minutes
Referral
Symptom to Hosp.
Invasive
Symptom to Hosp.
0
60
admit to transfer transfer
Door to PCI
Door to PCI (Balloon)
120
minutes
180
ACC 2002; Oral presentation
240
DANAMI-2
Transfer problems
• AF in 2.5%
• VT in 0.2%
• VF 1.4%
• 2/3 heart block in 2.3%
• 0 intubations
• 0 deaths
DANAMI-2: 30 day Primary Endpoint
All Patients
20
Accel. t-PA (n=782) PCI (n=790)
% of Patients
p = 0.0003
15
13.7
p = 0.35
10
8.0
7.6
p < 0.001
6.6
6.3
5
1.6
0
Combined*
Death
*Primary Endpoint: Death, Reinfarction, or Stroke
Reinfarction
p = 0.15
2.0
1.1
Disabling
Stroke
ACC 2002; Oral presentation
DANAMI-2: 30 day Primary Endpoint*
Referral vs. Invasive Hospitals
20
% of Patients
p=0.0003
15
p=0.002
p=0.048
14.2
13.7
Accel. t-PA PCI
12.3
10
8.5
8.0
6.7
5
0
All patients
(n=1572)
Referral hospitals Invasive Centers
(n=1129)
(n=443)
*Primary Endpoint: Death or Reinfarction or Stroke
ACC 2002; Oral presentation
DANAMI 2: Time to treatment
30 day results
20%
18%
16%
14%
12%
10%
8%
6%
4%
2%
0%
PCI
tPA
<1.5hrs
1-5-2.5hrs
2.5-4hrs
>4-12hrs
Combined end-point - All significant
DANAMI 2: Results by age group
30 day results
30%
25%
20%
PCI
tPA
15%
10%
5%
0%
<55yrs
55-64
65-74
75+
Combined end-point - All significant
PRAGUE 2
421
T'lysis
Time to treatment
245 minutes
429
Transport
425 transported
2 died and 3 VF
in transit
1.2% complications
4 stayed
Early Shock
T'lysis
3 died
Time to treatment
277 minutes
(+32 minutes)
Widimsky P et al, ESC 2002
PRAGUE 2: 30 day mortality
16%
P=0.12
P=NS
P<0.02
14%
12%
10%
PCI
SK
8%
6%
4%
2%
0%
Death
0-3hrs
3-12hrs
Widimsky P et al, ESC 2002
Trial stopped early because of reluctance to enrol patients >3 hours
Shock patients
Hochman JS et al, NEJM 1999;341:625-34
Transfer patients
Thrombolysis
IABP
PCI
CABG
PCI or CABG
Revascularisation
patients n=152
55.3%
49.3%
86.2%
54.6%
37.5%
86.8%
Medical Therapy
patients n=150
55.3%
63.3%
86%
14%
11.3%
25.3%
Ambulance transfer
Strategy for centres with door-to-balloon
times >120 mins?
• Send anyway for primary PCI?
• Make do with best lysis strategy?
• As above and select out patients for rescue?
• Conventional lysis and send for rescue on
arrival if required?
• Half-dose lysis ± GP IIb/IIIa inhibitor and
send?
Facilitated PCI
• Studies such as PACT, SPEED, TIMI-14 and
GUSTO V suggest that
– combination pharmacotherapy may improve
effects of fibrinolysis, and
– pharmacotherapy combined with a PCI
strategy may improve results of PCI
• FINESSE and ASSENT IV ongoing
• High risk patients who cannot be treated with
early PCI
Current Process for Infarct
Angioplasty
MI
Ambulance
Centre
MI Centres
MI
Ambulance
Centre
Lysis
DANAMI-2 - Time from Symptom Onset
to Admission and Time from Door to Rx
Potential impact of MI centres
Hospital
Referral
Symptom to Hosp.
Invasive
Symptom to Hosp.
Door to t-PA
Door to t-PA
1° PCI
Could reduce time
by 50-60 mins
Referral
Symptom to Hosp.
Invasive
Symptom to Hosp.
0
60
transfer
Door to PCI
Door to PCI (Balloon)
120
minutes
180
Paradox: referral patients might get more rapid reperfusion!
240
MI Centres
MI
Ambulance
Centre
Ambulance
Centre
As per C-PORT
MI
Emergency Ambulance Service
Hartlepool
3
Stockton
3
Carlton How
1
Redcar
3
Middlesbrough 3
Coulby Newham 1/2
Blue light trained 1
Government policy
Is there one?
• Get the best out of the old treatments before looking at new
ones
• Pilot studies of pre-hospital lysis
– But data already available from Scotland, N. Ireland,
France, Holland, Germany, Belgium, USA and Israel!
A better approach?
• Get the best out of the old treatments and look at new ones
• Look at studies of pre-hospital lysis and allow (ie fund)
introduction (?via NICE)
• Look at studies of primary PCI and allow (ie fund) introduction
(?via NICE)
Conclusions
If clinical investigators can
organise trials, then governments,
commissioners and clinical
cardiologists should be able to
organise an infarct angioplasty
service
Conclusions
Patient transfer in AMI
• Feasible
• Cardiovascular events are uncommon
• Need paramedics, ALS trained nurses or doctors
• Appropriately equipped ambulances
– Continuous ECG monitoring
– Defibrillation
– Mechanical ventilation
– Thrombolytic agents
– IV fluids
– Resuscitation drugs
– Ability to transfer IABP
• Need new law to oblige rapid ambulance response to AMI
transfer requests (<8 minute response time)
Conclusions
Primary PCI vs Fibrinolysis
• If hospital fibrinolysis is local strategy, change to primary PCI,
at least for all patients presenting >3 (?>2) hours after symptom
onset
• If pre-hospital fibrinolysis is local strategy, need appropriate
numbers of appropriately equipped and staffed ambulances
• Such a strategy requires a PCI strategy
– Contraindication to lysis
– Early shock
– High risk rescues
– Re-infarction
• If such ambulance crews exist, then use them for transfer for
primary PCI (as the PCI team exists anyway)!
Conclusions
• For PCI centres (on-site surgery) with 4 or
more interventionists –
– primary PCI should be preferred treatment
for STEMI
– ??offer fibrin-specific lysis to patients
presenting in first 3 hours at night)
• For PCI centres with off-site surgery Local arrangements needed for surgical
candidates.
Conclusions
• For centres that cannot offer PCI but transfer possible
within 3 hours – transfer patients to local PCI centre for primary
PCI
– ??offer fibrin-specific lysis to patients presenting
in first 3 hours – but respond to ongoing
problems).
• For centres that cannot offer PCI, when transfer within
3 hours not possible – use fibrinolysis but consider protocol for
immediate transfer of patients to PCI centre
(?all-comers or selective).
• Role of facilitated PCI to be determined
DANAMI 2: 30 day results
P<0.0001
25%
20%
15%
reMI
No reMI
10%
5%
0%
Death
DANAMI-2
600 day data (6months-4 years)
End-point
Combined All patients
Combined Referral
hospitals
Mortality All patients
Mortality Referral
hospitals
Fibrinolysis
24.2%
PCI
17.8%
P value
0.002
NNT
18
23.3%
16.9%
0.004
15
16%
13.4%
0.26
40
15.3%
11.9%
0.1
30
Anderson HR et al, XIVth World Congress of Cardiology 2002
Is simple primary PCI still going to be best?
Vermeer et al, Heart 1999;82:426-31
16%
14%
12%
10%
Conservative
Rescue
Primary PCI
8%
6%
4%
2%
0%
In-hospital mortality