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ORIGINAL ARTICLE
Transfer for primary angioplasty in elderly patients withacute myocardial infarction
FRANCESCO LIISTRO, PAOLO ANGIOLI, KENNETH DUCCI, GIOVANNI FALSINI,
SILVIA BALDASSARRE, ROSSELLA BRANDINI & LEONARDO BOLOGNESE
Department of Cardiovascular Disease, San Donato Hospital, Arezzo, Italy
AbstractIntroduction: The aim of this study was the evaluation of an immediate transfer for primary angioplasty (PPCI) in elderly(age]75 years) patients with ST elevation acute myocardial infarction (STEMI). Methods and materials: All elderly patientswith STEMI admitted for PPCI from June 2002 to October 2005, were enrolled. Major Adverse Cardiac Events (MACE)were collected at 6 months. Results: 133 patients (group 1) were admitted directly and 154 patients (group 2) weretransferred from peripheral hospitals. Ischemia time was 2489146min in group 1 and 2769169 min in group two (PB0.001); door-to-balloon time was 60930 min in group 1 and 90945 min in group two (PB0.0001). At 6 months cardiacdeath occurred in 15 (11%) and 16 (10%) patients in group 1 and 2 respectively (P�NS), MI in 3(2%) and 2(1%)respectively (P�NS), clinically driven target lesion revascularization in 6(4%) and 5(3%) respectively, for an overall event-free survival rate of 82% in group 1 and 83% in group 2 (P�NS). Logistic regression analysis showed age (OR: 1.04.1; 95%CI: 1.0�1.2; P�0.049) Killip class ]2 (OR: 4.6; 95% CI: 1.3�16.4; P�0.01) to be the only independent predictors of6-month cardiac mortality. Conclusion: Systematic transfer of elderly STEMI patients for PPCI, with a door-to-balloon timeB1 h, leads to clinical results similar to those achievable in patients who present directly in hospital with cath.-lab. facilities.
Key Words: Primary angioplasty, elderly, STEMI, clinical outcome
Introduction
Elderly patients constitute approximately 30% of
patients requiring medical care for ST elevation
acute myocardial infarction (STEMI). As reported
in recent registries focusing on STEMI treatment,
less than 50% of these patients are treated with
reperfusion, and less than 30% with primary angio-
plasty (PPCI) (1,2). The reluctance to persecute a
reperfusion strategy in the elderly is probably due to
the higher incidence of co morbidities, the worse
coronary anatomy scenario and clinical conditions
which reduce the efficacy of such strategies and
enhance the incidence of complications (acute renal
failure, major bleeding) compared to younger popu-
lation (3,4). Older age is one of the key predictors of
failure to use reperfusion therapy in otherwise
eligible patients (5,6). The proportion of ‘ideal’
elderly patients receiving reperfusion therapy de-
creases as age increases (64.8%, 65 to 69 years;
60.1%, 70 to 74 years; 50.4%, 75 to 79 years;
35.4%, 80 to 84 years; 20.4%, ]85 years) (7). As
observed in younger patients, PPCI is the preferred
treatment strategy for elderly patients with STEMI,
due to the higher rate of reperfusion and the lower
rate of bleeding complications compared to throm-
bolysis (8�11). In reality, only a minority of patients
experiencing STEMI present directly to PCI cen-
ters, where perhaps the trial conclusions can be
applied. In ‘real’ life, the majority of patients, even in
well-resourced countries, initially present to their
emergency ambulance service and/or to local hospi-
tals rather than to an angioplasty centre. In this
situation, the clinical decision needs to be made
between early thrombolysis or transfer to a PCI
centre with delayed, but more complete, reperfu-
sion. Despite the greater incidence and risk of
STEMI among older patients (5,12,13), several
large randomized clinical trials evaluating reperfu-
sion therapy for the treatment of these patients or
the relative merits of mechanical versus chemical
reperfusion, have systematically excluded elderly
patients (14,15). Even trials that have included older
patients have substantially underrepresented them,
Correspondence: Francesco Liistro, Department of Cardiovascular Disease, San Donato Hospital, Arezzo, Italy. E-mail: [email protected]
(Received 6 December 2007; accepted 16 March 2008)
Acute Cardiac Care. 2008; 10: 152�158
ISSN 1748-2941 print/ISSN 1748-295X online # 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.1080/17482940802084986
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with only 10% to 15% of the populations being�75
years of age (7). Thus, much less is known about the
risk/benefits of reperfusion therapy or the optimal
reperfusion strategy among the elderly with STEMI.
The Senior PAMI trial (16) demonstrated a super-
iority of PPCI over thrombolysis in elderly STEMI
patients on 30-day incidence of combined end-point
of death-stroke-reinfarction. However, few data are
available regarding elderly patients transferred from
peripheral hospitals for PPCI.
The hypothesis that was tested in this registry is
that primary PCI in elderly patients transferred from
peripheral hospital with a mean door to balloon
delay B1 h could lead to similar clinical results
obtained in elderly patients with AMI admitted
directly in hospital with cath.-lab. facilities.
Materials and methods
All elderly STEMI patients eligible for PPCI ad-
mitted in our cath.-lab. from June 2002 to October
2006 where enrolled in a registry and followed
prospectively. Cardiac care in the Arezzo district
(Tuscany, Italy, 350,000 inhabitants) is provided
largely via 5 hospitals. The Department of Cardiol-
ogy in the S. Donato Hospital, Arezzo, offers a 24-h
PPCI service on a routine basis (on-call) for patients
with acute STEMI, and central triage for STEMI
patients by the Emergency Ambulance Service was
implemented according to a hub-and-spoke model.
All hospitals participating to the network dist no
more than 35 Km from the hub hospital, with a
mean transport time from all district hospitals to
cath.-lab. of approximately 30 min. The primary
diagnosis of acute STEMI and triage of patients to
PPCI was performed by physicians of the Emer-
gency Ambulance Service or of the five hospitals for
prompt organization of transfer to the catheteriza-
tion laboratory. At the same time, a prospective
registry was established for quality control purposes.
Relevant data (patient characteristics, risk markers,
ECG parameters, time intervals, therapeutic ap-
proaches, and clinical follow-up) were collected
and entered into a computer database.
Patients were considered eligible for PPCI if
presenting within 12 h from symptom onset with
persistent elevation of ST segment �1 mm in two
contiguous leads, free from other life treating disease
(advanced cancer, dementia) and if they provided
signed informed consent. Patients in cardiogenic
shock were included in the analysis.
Ischemia time was defined as the time between
symptoms onset and balloon angioplasty. Door-to-
balloon time was defined as the time between
hospital admission and balloon angioplasty. In
transferred patients, this time interval is the time
from admission in the local hospital to balloon
angioplasty at the PCI center. Patients transferred
from local hospitals or directly from home to the PCI
center always skipped the PCI center emergency
ward and were directly transported to the cath.-lab.
Aspirin (bolus of 325 mg per os 500 mg ev the
day of admission followed by 100 mg per os daily)
and unfractioned heparin (bolus of 70 UI/kg body
weight ev followed by infusion 10 UI/kg/h) were
administered in the emergency department or di-
rectly in the cath.-lab.
IIb�IIIa inhibitors were used according to physi-
cian’s choice in relation to patient’s bleeding risk.
Heparin was adjusted to achieve an activated clot-
ting time of �350 s in patients not receiving IIb�IIIainhibitors and 200 to 300 s in IIb�IIIa inhibitors-
treated patients. Abciximab was given as a 0.25-mg/
kg intravenous bolus followed by a 0.125-mg/kg
per min infusion for 12 h. Tirofiban was given as a
25 mcg/kg followed by a 0.15 mcg/Kg/min.
Treatment with clopidogrel (300 mg bolus) or
ticlopidine (500 mg daily) was started either in the
emergency department or directly in the cath.-lab.
and continued for at least one month in case of bare
metal coronary stent implantation.
Coronary revascularization
PCI was performed according to standard techni-
ques. In case of multivessel disease, only the culprit
lesion (according to the ST-segment elevation on
ECG and wall motion abnormalities on Echocardio-
graphy) was treated. The remaining coronary ste-
nosis was treated thereafter according to clinical
status. Procedure was defined successful if TIMI 3
flow and residual stenosis B50% were achieved.
Measurement of cardiac enzymes was performed
in all patients before coronary angioplasty and every
six hours after myocardial revascularization until the
values normalized.
Major adverse cardiac events (MACE) were
defined as follows:
. Death was considered of cardiac origin except
for those of a known different origin.
. Reinfarction was diagnosed by the presence of
either of the following: (1) elevation of CK or
its isoform to at least twice the upper limit of
the normal reference range; (2) development
of a new Q wave on the ECG in at least two
contiguous leads.
. Ischemic driven target lesion revascularization
(IDTLR) was defined as any repeat percuta-
neous coronary intervention or aorto-coron-
ary bypass surgery due to lumen re-narrowing
within the stent or in the 5 mm distal or
proximal segments associated with symptoms
or objective signs of ischemia
MACE were collected at 30-day and on long-
term outcome. Follow-up was obtained by patient’s
visit or telephone interview.
Transfer for primary PCI in the elderly 153
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Statistical analysis
Nominal Variables were compared by using Fisher
exact test; continuous variables were compared with
t-test. A P value B0.05 was considered statistically
significant. Kaplan-Meyer analysis was performed to
assess event free survivals and cardiac death at six
months. Logistic regression was performed to ad-
dress independent predictors of six-month cardiac
mortality on the two separate groups; all variables
reported in Tables I and II were considered in the
analysis. All statistical computations were performed
with the SPSS 10.0 statistical package.
Results
Baseline clinical characteristics
During the study period, 1102 patients with STEMI
were admitted in our Department. Among these
patients, 360 were elderly (32%), 73 of whom were
not eligible for reperfusion and were treated con-
servatively and 287 (80%) patients underwent PPCI
and constituted the study population. 133 patients
(group 1) were admitted directly in the hospital with
cath.-lab. facilities and 154 patients (group 2) were
transferred from peripheral Hospitals. Overall, 20
patients, 11 in group 1, and 9 in group 2 (P�0.3)
were in cardiogenic shock.
Basic clinical characteristics of the two patient
populations is reported in Table I. No significant
differences were noted between the two groups
except for previous percutaneous coronary interven-
tion (PCI) that was higher in group 1.
Treatment and time delay
Time between symptoms onset and balloon angio-
plasty (ischemia time) was 2489146min in group 1
and 2769169 min in group two (PB0.001). Time
between hospital admission and balloon angioplasty
(door-to-balloon time) was 60930 min in group 1
and 90945 min in group two (PB0.0001). No
adverse events occurred during ambulance transpor-
tation among patients of group 2. Glycoprotein IIb�IIIa inhibitors were used in 158 patients (55%), 64
(48%) of group 1 and 94 (61%) of group 2 (P�0.049). Among patients of group 2 who received
IIb�IIIa inhibitors, the drug was administered before
transportation in 58 (38%). Angiographic analysis
and myocardial revascularization data are reported
in Table II. Coronary angiography showed multiple
vessel disease in 92(69%) patients of group 1 and
111 (72%) of group 2 (P�NS). No significant
differences in terms of baseline TIMI 0�1 flow;
vessel diameter and final minimal lumen diameter
(MLD) were observed. Coronary stents were im-
planted in more than 90% of patients in both
groups. Procedure was successful in 91 (95%)
patients of group 1 and 108 (95%) of group 2.
Clinical outcome
Thirty-day and six-month clinical outcome is re-
ported in Table III. At 30 days, death occurred in 13
(10%) patients of group 1 and 16 (10%) of group 2
(P�0.9). Patients in cardiogenic shock had a �50%
in-hospital mortality in both groups, while patients
not in cardiogenic shock showed a cardiac mortality
rate of 6.5% in group 1 and 7.5% in group 2, P�0.8. Reinfarction due to stent thrombosis occurred
in 1 (0.8%) patients of group 1 and 1(0.6%) of
group 2 (P�0.9), all treated with successful re-
angioplasty. One patient underwent successfully
cardiac surgery for inter ventricular septum rupture.
2 patients treated with abciximab, 1 in each group,
suffered from retroperitoneal bleeding which was
treated medically with blood and fluid transfusion
Table I. Baseline clinical characteristics.
Group 1
133 patients
Group 2
154 patients P
Male sex n (%) 70 (52) 78 (51) 0.9
Age (m9SD) 8194.8 8094.7 0.8
Current smoker n (%) 18 (13) 13 (8) 0.2
Diabetes n (%) 18 (13) 28 (18) 0.1
Family history of CAD n (%) 17 (13) 21 (14) 0.5
Hypertension n (%) 55 (40) 66 (43) 0.7
Hypercholesterolemia n (%) 9 (7) 18 (12) 0.07
History of CAD n (%) 18 (13) 18 (12) 0.2
Previous PCI n (%) 7 (5) 3 (2) 0.07
Creatinine �1.3mg/dL n (%) 28 (20) 25 (16) 0.3
PAD n (%) 7 (5) 11 (7) 0.4
Ischemia Time (min9SD) 2489146 2769169 0 B001
Door-to-balloon time (min9SD) 60930 90945 0 B0001
LVEF 44910 46910 0.2
Cardiogenic shock 11 (8) 9 (6) 0.3
2b3a inhibitors n (%) 65 (48) 91 (59) 0.049
CAD, coronary artery disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; PAD, peripheral artery disease; LVEF,
left ventricle ejection fraction.
154 F. Liistro et al.
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without relevant clinical sequel. The cumulative
MACE-free survival rate was 89% in both groups.
At 6 months, overall mortality rate was 13% (18
patients) in group 1 and 12% (19 patients) in group
2 (P�0.8). Cardiac death occurred in 15 (11%) and
16 (10%) patients in group 1 and 2 respectively (P�0.9). MI in 3 (2%) and 2 (1%) respectively, IDTLR
in 6 (4%) and 5 (3%) respectively (P�0.7), for an
overall event-free survival rate of 82% in group 1 and
83% in group 2 (P�0.9). Kaplan-Meyer analysis for
event free survival and cardiac death is reported in
Figures 1 and 2 respectively. Logistic regression
analysis showed age (OR: 1.04.1; 95% CI: 1.0�1.2;
P�0.049) Killip class ]2 (OR: 4.6; 95% CI: 1.3�16.4; P�0.01) to be the only independent predic-
tors of six-month cardiac mortality.
Among patients that received IIb�IIIa inhibitors,
cardiac mortality was 10% (16 patients) versus 12%
(15 patients) in those who did not receive the
medication (P�0.3)
Discussion
As reported in previous studies (2,17), our results
confirm that elderly patients represent a significant
portion (approximately 30%) of the total population
requiring urgent coronary revascularization for
STEMI. The clinical value of PPCI emerged clearly
in our series with six-month cardiac mortality as low
as 10%, which was most influenced by the high
mortality rate (50%) observed in patients with
cardiogenic shock. The data compare favorably
with those reported in the literature concerning the
use of thrombolysis as primary strategy in these
clinical settings. In the GRACE registry (18), in-
hospital mortality was 27% in elderly STEMI
patients who did not receive any reperfusion and
24% in those receiving thrombolysis. Same results
appeared in a large meta-analysis of thrombolysis
trials in the elderly with a 30-day mortality of 26%
(19). The clinical advantage of PPCI versus throm-
bolysis in the elderly was also demonstrated in the
MITRA-MIR registries (11). However, a recent
randomized trial comparing PPCI vs. thrombolysis
in patients older than 70 years, reported a 30-day
mortality in the lytic arm of only 13% versus 10% in
the PCI arm (P�NS), and the interventional
strategy was superior to lyses only if the combined
endpoint of death-reMI-cerebrovascular accident
was considered (16). It has to be underline that the
age cut-off of 70 years adopted in this study differs
Table III. Clinical outcome.
Group 1
133 patients
Group 2
154 patients P
30 day
Death 13 (10) 16 (10) 0.8
Patients in shock 5/11 (45) 5/9 (55) 0.9
Patients not in shock 8/122 (6.5) 11/145 (7.5) 0.8
Re-MI 1 (0.8) 1 (0.6) 0.8
IDTLR 1 (0.8) 1 (0.6) 0.8
Patients free from MACE 119 (89) 137 (89) 0.5
6 months
Overall mortality 18 (13) 19 (12) 0.9
Cardiac death 15 (11) 16 (10) 0.9
MI 3 (2) 2 (1) 0.8
IDTLR 6 (4) 5 (3) 0.7
Patients free from MACE 109 (82) 126 (83) 0.9
MI, myocardial infarction; IDTLR, ischemia driven target lesion revascularization; MACE, major adverse cardiac event; PCI, percutaneous
coronary intervention.
Table II. Procedural characteristics.
Group 1
133 patients
Group 2
154 patients P
Multivessel disease n (%) 92 (69) 111 (72) 0.9
Left main significant stenosis n (%) 9 (7) 10 (6) 0.8
LAD as IRA n (%) 66 (50) 78 (50) 0.6
Lesion length (mm) (M9SD) 13.395.5 13.294.5 0.9
RVD (mm) (M9SD) 2.9790.44 2.9790.38 0.9
Basal MLD (mm) (range) 0 (0�0.67) 0 (0�0.79) 0.6
Final MLD (mm) (M9SD) 2.890.6 2.990.4 0.1
Stented patients 122 (92) 143 (93) 0.7
Complete revascularization n (%) 44 (33) 64 (41) 0.2
Baseline TIMI-0-1 n (%) 106 (79) 111 (72) 0.1
Final TIMI 3 n (%) 127 (95) 148 (96) 0.8
LAD, left anterior descending artery; IRA, infarct related artery; RVD, reference vessel diameter; MLD, minimal lumen diameter.
Transfer for primary PCI in the elderly 155
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from the one accepted worldwide (75 years) for the
definition of elderly patients and therefore any
comparison with this study is potentially biased
due to the importance of increasing age on the
outcome of acute coronary syndromes in the elderly
(17). In addition, this trial excluded elderly patients
in cardiogenic shock who experience the highest
mortality rate (50% in our registry). The role of
PPCI in elderly STEMI patients in cardiogenic
shock is controversial: the SHOCK trial (20) did
not showed any benefit associated with PPCI in the
elderly while elderly STEMI patients enrolled in the
SHOCK (21) registry (44) who undergone PPCI
had a 50% mortality reduction compared to patients
who were treated conservatively.
Our study faced the problem of the clinical
decision-making concerning the transfer for PPCI
or immediate reperfusion by thrombolysis in elderly
patients presenting in hospitals without cath.-lab.
facilities. Although several randomized trials and
subsequent meta-analysis demonstrated a clinical
benefit of transfer STEMI patients for PPCI com-
pared to on-site thrombolysis strategy (22�24),
elderly patients were significantly underrepresented
in those studies and an important bias would appear
when applying to them the overall results. Systema-
tic transfer for PPCI in elderly STEMI patients
appeared feasible in our registry with an acceptable
delay in terms of door-to-balloon time, entirely due
to patient’s transportation with a mean value of 90
min. In addition, the transfer strategy appeared to be
safe and no adverse event occurred during transpor-
tation. Myocardial revascularization was successful
in 95% of patients in both groups. This rate of
reperfusion is much higher than 60% reported in
trials with thrombolysis (19).
Age and Killip class ]2 were the only indepen-
dent predictors of 6-month cardiac mortality. There
was no significant relation between cardiac mortal-
ity, door-to-balloon time, and ischemia time. This
observation might be explained by the small differ-
ence (mean 30 min) in door-to-balloon time and in
ischemia-time between the two patients cohorts, and
suggest that PPCI in elderly patients transferred
from peripheral hospitals may lead to same clinical
results obtained in patients directly admitted in
hospital with cath.-lab. facilities if the transfer delay
is less than 1 h. The small difference in door-to-
balloon time between patients admitted directly and
those transferred from local hospitals was probably
due to the constant availability of ambulance service
(which foreshortened the patient turn-around at the
local hospital), short distances (�35 km) and direct
transport to the cath.-lab., skipping the PCI center
emergency ward. Accordingly, the time difference
between the two groups is mainly due to the actual
patient transportation. The use of glycoprotein IIb�IIIa receptor antagonists appeared safe in our
registry among elderly patients, with a very low
incidence of major bleeding and no occurrence of
intra-cerebral hemorrhage. However, the use of GP
IIb�IIIa was not associated with a mortality reduc-
tion. This observation was also reported by Gua-
gliumi et al. (25).
The clinical benefit of coronary stenting in PPCI
is reported in the CADILLAC study (26) including
a sub-analysis in the elderly (25). Accordingly, the
rate of coronary stenting in our registry was 90% and
the clinical value of this strategy seems to be
supported by the very low clinically driven TLR
rate (3%) observed at six months. Our results are in
contrast with those reported by De Luca et al. (27)
who sustained that coronary stenting in elderly MI
patients do not provide any advantages compared to
balloon angioplasty.
Study limitations
The present study suffers all the limitations of
observational and registry studies. Thus, some
biases may invalidate the observed rate of cardiac
events between the two groups. However, the study
has the advantage of providing data that are a
reflection of therapeutic strategy and outcomes in
the entire community and that might be moreFigure 2. Kaplan-Meyer curve for patients free from cardiac
death at six months.
Figure 1. Kaplan-Meyer curves for patients free from major
adverse cardiac events (MACE) at six months.
156 F. Liistro et al.
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generalizable than those from the more selected
population entered into randomized trials. The out-
come results, however, reflect those of patients
admitted to a Cardiovascular Department, and
may not apply to all of the elderly patients with a
final diagnosis of myocardial infarction admitted to
non-cardiological units. In addition, restriction of
the registry to patients who are admitted to the
Cardiovascular Department may have resulted in
the exclusion of patients who died early on arrival in
the emergency department.
Conclusions
The results of this study show that a systematic
transfer of elderly STEMI patients for PPCI is
feasible and leads to clinical results similar to those
achievable in patients who present directly in hospi-
tal with cath.-lab. facilities, at least for distances
which determine an increase in door-to-balloon time
B1 h.
Declaration of interest: The authors report no
conflicts of interest. The authors alone are respon-
sible for the content and writing of the paper.
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