SCIENCE VOLUNTEER WARNING SIGNS DONATE

This site uses cookies. By continuing to

browse this site you are agreeing to our use
of cookies. × ×
Click here for more information.

% & Sections
AboutACCESS ' Tools (
" FREE | RESEARCH ARTICLE

Association of Anemia With

Outcomes Among ST-Segment–
Elevation Myocardial Infarction
Patients Receiving Primary
Percutaneous Coronary Intervention
Nima Moghaddam#, MD Graham C. Wong, MD, MPH
John A. Cairns, MD Shaun G. Goodman, MD, MSc
Michele Perry-Arnesen, MHA, RN Wendy Tocher, RN
Martha Mackay, PhD, RN Joel Singer, PhD Terry Lee,
PhD Sunil V. Rao, MD Christopher B. FordyceMD,
MHS, MSc
Originally published 14 Dec 2018
https://doi.org/10.1161/CIRCINTERVENTIONS.118.007175
Circulation: Cardiovascular Interventions. 2018;11

This article is commented on by the following: $

Abstract
Background:
Anemia may confer a poor prognosis among
patients with the acute coronary syndrome.
However, few data exist on the association of
anemia with in-hospital outcomes, including
bleeding, among ST-segment–elevation
myocardial infarction patients receiving primary
percutaneous coronary intervention.

Methods and Results:

We identified 1919 ST-segment–elevation
myocardial infarction patients who had
undergone primary percutaneous coronary
intervention within the Vancouver Coastal
Health Authority (2007–2016) of whom 322
(16.8%) had anemia on admission. Between-
group differences in (unadjusted) in-hospital
outcomes, including heart failure, cardiogenic
shock, major bleeding, and death were
examined. Spearman correlation (rs) and
multivariate logistic regression were used to
evaluate the relationship of anemia on
admission with clinical outcomes. Compared
with nonanemic patients, anemic patients were
more likely to have preexisting hypertension,
diabetes mellitus, and prior myocardial
infarction. Anemic patients had higher
unadjusted rates of in-hospital death (8.1%
versus 3.7%; P<0.001), bleeding (18.2% versus
9.4%; P<0.001), and were more likely to
develop heart failure (odds ratio [OR], 1.62; 95%
CI, 1.19–2.22), shock (OR, 2.35; 95% CI, 1.62–
3.40), or cardiac arrest (OR, 1.94; 95% CI, 1.10–
3.40) during their hospital stay. Baseline anemia
was independently associated with major
bleeding (OR, 1.78; 95% CI, 1.25–2.56) but not)
all-cause mortality (OR, 0.99; 95% CI, 0.57–
1.73). There was no significant correlation
between anemia and overall reperfusion times
(OR, 0.95; 95% CI, 0.74–1.22).

Conclusions:
In a contemporary ST-segment–elevation
myocardial infarction cohort receiving primary
percutaneous coronary intervention, nearly 1 in
5 patients were anemic. Anemia was associated
with increased comorbidities and higher-risk
features on presentation and was independently
associated with subsequent major in-hospital
bleeding but not all-cause mortality. These
results suggest that anemic ST-segment–
elevation myocardial infarction patients may
safely receive timely primary percutaneous
coronary intervention but with particular
consideration for bleeding avoidance strategies.

WHAT IS KNOWN
Anemia is common among patients
with the acute coronary syndrome,
but its association with reperfusion
times and adverse clinical outcomes
among ST-segment–elevation
myocardial infarction patients
undergoing primary percutaneous
coronary intervention is unclear.

Reperfusion therapy may be lower in

the anemic patients.

Earlier studies suggest that the

presence of anemia may deter
interventionalists from performing
percutaneous coronary intervention
given trends in public reporting of
acute coronary syndrome outcomes.

WHAT THE STUDY ADDS

Our results confirm that anemia is
associated with greater comorbidities
and higher-risk features on hospital
presentation.

Anemia was not associated with

prolonged overall reperfusion times
compared with nonanemic patients.

Anemia was independently

associated with major bleeding but
not all-cause mortality suggesting
that anemic ST-segment–elevation
myocardial infarction patients can
safely receive timely primary
percutaneous coronary intervention.

Introduction
See Editorial by Dauerman and Bhatt

Anemia is prevalent among patients with the

acute coronary syndrome (ACS) and has been
associated with poor clinical prognosis.1,2
Although some studies have found that lower
hemoglobin level on admission is an
independent predictor of in-hospital, short-term,
and long-term mortality in patients with ST-
segment–elevation myocardial infarction
(STEMI),3,4 others have shown no such
association.5,6 There is a similarly inconsistent
association of anemia with adverse clinical
outcomes among STEMI patients undergoing
primary percutaneous coronary intervention
(pPCI).7–9 Clinical guidelines do not provide
definitive recommendations for the
management of anemia in STEMI patients
undergoing pPCI,10 and the optimal transfusion
threshold remains controversial.11–13 There is
also recent concern in some regions that public
reporting of acute MI outcomes may create
disincentives to provide PCI in patients with
greater severity of illness, including those with
anemia.14,15 Furthermore, although some
studies have reported differences in care
processes (such as duration or choice of
antiplatelet agents and revascularization
strategies16) between anemic and nonanemic
patients, data on the association of anemia with
reperfusion times remain scarce.17,18

The aims of the present study are to (1)

determine the relationship between admission
hemoglobin level and clinical presentation
among a large regional STEMI cohort
undergoing pPCI; (2) describe the association of
baseline hemoglobin concentrations with major
adverse cardiac events post-pPCI; and (3)
investigate the association between anemia and
reperfusion times for pPCI.

Methods

Study Population
The data, analytic methods, and study materials
will not be made available to other researchers
for purposes of reproducing the results. This
was a retrospective analysis of the prospective
Vancouver Coastal Health Authority STEMI
registry.19 We included all 2031 patients with
STEMI who underwent successful pPCI at
either of the 2 quaternary hospitals within the
Vancouver Coastal Health Authority region
between June 26, 2007, and March 31, 2016.
We excluded patients with missing admission
hemoglobin data (n=21) and those with STEMI
complicated by an out-of-hospital cardiac arrest
(n=91) because out-of-hospital cardiac arrest is
independently associated with higher in-
hospital mortality.20 After exclusions, the final
sample size was 1919 patients (Figure 1).

Download figure | Download PowerPoint

Caption $

Definitions
Anemia was classified in accordance with the
World Health Organization definitions:
hemoglobin <130 g/L in men and <120 g/L in
women.21 Laboratory values were recorded
from the blood collected before the pPCI. Heart
failure (HF) was defined as clinical symptoms,
examination findings (Killip class 2–4), or
imaging evidence of pulmonary edema on
admission. In-hospital mortality was defined as
death from any cause. Cardiogenic shock was
characterized as cardiac index <2.2 mL/min per
m2 or systolic blood pressure <90 mm Hg
persisting for >30 minutes. Major bleeding was
identified as a bleeding event during the index
hospitalization that was associated with
significant blood loss (hematocrit drop of at
least 10% or a hemoglobin drop of at least 30
g/L) requiring transfusion of whole blood,
packed red blood cells, or use of a surgical or
procedural intervention to manage the bleeding.
The composite end point comprised HF,
cardiogenic shock, major bleeding, or death.
First medical contact (FMC) was defined as the
time at which a health care provider was at the
patient’s side; this would be the time of triage at
the first emergency department for patients who
transported themselves to the hospital or the
time of arrival of a paramedic at the side of the
patient for emergency medical services users.
The optimal FMC-to-device times were
obtained from the 2015 Canadian
Cardiovascular Society consensus document
on quality indicators for PCI which endorses a
reperfusion time goal of <90 minutes for
patients presenting to PCI centers and <120
minutes for patients presenting to PCI
noncapable hospitals.22 A prolonged
reperfusion time was defined as FMC-to-device
time of >90 and >120 minutes in PCI-capable
and PCI-noncapable facilities, respectively.

Statistical Analysis
The data, analytic methods, and study materials
will not be made available to other researchers
for purposes of reproducing the results. All data
were analyzed with Statistical Analysis System
(SAS) software version 9.2 (SAS Institute, Cary,
NC). Patients were grouped according to the
presence of anemia at admission. Continuous
variables were measured as medians with
interquartile range or means±SDs, and
categorical variables were measured as
percentages. Comparisons between the anemic
and nonanemic groups were performed using
the Kruskal-Wallis test or ANOVA for continuous
variables and the χ2 or Fisher exact test for
categorical variables as appropriate. Baseline
hemoglobin levels were considered as both
categorical (ie, anemic versus nonanemic) and
continuous in our analysis. Spearman
correlation (rs) was used to measure the
strength and direction of association between
admission hemoglobin concentration and
relevant ranked variables. Unadjusted and
adjusted odds ratios were calculated using a
logistic regression model. Adjustment variables
included the following prognostically important
clinical characteristics: age, sex, hypertension,
diabetes mellitus, HF on presentation, territory
of infarct, prolonged reperfusion times, initial
heart rate, and systolic blood pressure.23 The
clinically important adjusted variables were
selected a priori. As a sensitivity analysis, a
regression analysis based on propensity score
adjustment was conducted. The propensity
scores were derived using the same set of
variables as stated above. The statistical
models were not adjusted for multiple
comparisons. Statistical significance was
determined as a P value of <0.05. This study
was approved by the clinical research ethics
board of the University of British Columbia.

Results

Distribution of Hemoglobin Values

There were 1919 patients who met the inclusion
criteria, of whom 322 (16.8%) had anemia. The
mean initial hemoglobin of the study population
was 141.0±17.6 g/L with a mean hemoglobin of
146.5±12.5 g/L in the nonanemic cohort and
113.7±12.9 g/L in the anemic patients. A
histogram representing the distribution of the
admission hemoglobin concentrations in the
entire study population is shown in Figure 2.

Download figure | Download PowerPoint

Caption $

Baseline Clinical Characteristics

Table 1 displays the baseline demographics and
clinical characteristics of the STEMI patients
referred for pPCI. Anemia was more common in
females, patients aged ≥65 years, and those
with hypertension, diabetes mellitus, and prior
cerebrovascular or cardiovascular events.
Anemic patients presented more often in
cardiogenic shock or HF on arrival to hospital.
Infarct location was not different between the 2
groups. In terms of antithrombotic use during
index hospitalization, anemic patients were less
likely to receive unfractionated heparin.
Although aspirin administration was not
different between patients with and without
baseline anemia, anemic patients were less
frequently prescribed ticagrelor and more likely
to receive clopidogrel instead (Table 2).

Table 1. Baseline Characteristics and Clinical

Features on Presentation

Anemia
Patient P
Characteristics No Value
Yes (n=322)
(n=1597)

Baseline comorbidities

62.5
72.6 (62.8,
 Age, y (54.7, <0.001
82.2)
74.2)

 Age ≥65, n 681

221 (68.6) <0.001
(%) (42.6)

26.5
24.3 (22.0,
 BMI, kg/m2 (23.9, <0.001
27.1)
29.0)

 Female sex, n 321

115 (35.7) <0.001
(%) (20.1)

 Dyslipidemia, 668
148 (46) 0.182
n (%) (41.9)

 Hypertension, 808
208 (64.9) <0.001
n (%) (50.7)

 Diabetes 306
78 (24.2) 0.040
mellitus, n (%) (19.2)

 
468
Current/recent 79 (24.5) 0.085
(29.4)
smoker, n (%)

 Peripheral
vascular 43 (2.7) 15 (4.7) 0.060
disease, n (%)

 Prior heart
27 (1.7) 21 (6.5) <0.001
failure, n (%)

203
 Prior MI, n (%) 67 (20.9) <0.001
(12.8)

 Prior PCI, n 161

39 (12.1) 0.275
(%) (10.1)

 Prior CABG, n
31 (1.9) 13 (4) 0.022
(%)

 Prior stroke, n
80 (5) 41 (12.8) <0.001
(%)

Clinical features on presentation

 Heart failure
on presentation, 70 (4.4) 30 (9.4) <0.001
n (%)

 Cardiogenic
shock on 67 (5.7) 27 (12.6) <0.001
arrival, n (%)

 Initial heart 75.5 (62,

75 (60, 90) 0.786
rate (bpm) 88)

 Initial systolic 141

132.5 (110,
blood pressure (122, <0.001
152)
(mm Hg) 162)

 Initial
92 (78,
creatinine, 92 (76, 123) 0.167
109)
mmol/L

  96±26.9 113.4±101.9

 Anterior 840
186 (57.8) 0.090
infarct, n (%) (52.6)

 Initial
presentation to 1162
261 (81.1) 0.002
PCI hospital, n (72.8)
(%)

Values for continuous variables are presented

as medians with interquartile variables in the
parentheses and mean±SD. BMI indicates
body mass index; CABG, coronary artery
bypass grafting; MI, myocardial infarction;
and PCI, percutaneous coronary intervention.

Table 2. Antithrombotic Therapies at

Presentation and Discharge

Medication, n P
Nonanemia Anemia
(%) Value

Within 24 h of presentation

311
 Aspirin 1561 (98.4) 0.245
(97.5)

 P2Y12
<0.001
inhibitor

   234
1123 (70.9)
Clopidogrel (73.4)

69
  Ticagrelor 432 (27.3)
(21.6)

 
273
Unfractionated 1420 (89.8) 0.027
(85.6)
heparin

45
 Enoxaparin 261 (16.5) 0.287
(14.1)

 
2 (0.1) 1 (0.3) 0.428
Fondaparinux

46
 Bivalirudin 214 (13.5) 0.678
(14.4)

 Glycoprotein
166
IIb/IIIa 926 (58.7) 0.028
(52.0)
inhibitors

At discharge

293
 Aspirin 1525 (99.2) 0.684
(99.0)

 P2Y12
0.051
inhibitor

  Prasugrel 4 (0.5) 0 (0.0)

65
  Ticagrelor 468 (59.3)
(47.4)

   62
266 (33.7)
Clopidogrel (45.3)

In-Hospital Outcomes
The unadjusted outcomes by anemia status are
recorded in Table 3. Anemia was associated
with increased rates of adverse outcomes,
including in-hospital cardiac arrest (13.1%
versus 7.3%; odds ratio [OR], 1.94; CI, 1.10–
3.40), congestive HF (19.4% versus 12.9%; OR,
1.62; CI, 1.19–2.22), cardiogenic shock (14.4%
versus 6.7%; OR, 2.35; CI, 1.62–3.40), and
death (8.1% versus 3.7%; OR, 2.29; CI, 1.42–
3.69). Both instrumented and noninstrumented
major bleeding events occurred more frequently
in patients with baseline anemia (8.8% versus
5.6% and 9.4% versus 3.8%, respectively; OR,
2.14; CI, 1.54–2.98). Compared with nonanemic
patients, anemic patients were less likely to
have access site bleeding and more likely to
have to bleeding from gastrointestinal tract and
other sources (Table I in the Data Supplement).
This is despite slightly more use of femoral
access site (86.3%) in the anemic compared
with nonanemic patients (83.2%; Table II in the
Data Supplement). Anemic patients had longer
hospitalizations (median: 3.3 versus 3.0 days;
P<0.001), with an inverse relationship observed
between hemoglobin values and hospital length
of stay (rs=−0.6; P=0.006). Neither baseline
anemia nor hemoglobin concentration was
significantly associated with predischarge left
ventricular ejection fraction (rs=−0.01; P=0.793).

Table 3. Unadjusted In-Hospital Outcomes of

Patients With pPCI

Anemia
OR
Outcome (95%
No Yes CI)*
(n=1597) (n=322)

LVEF (mean %) 47.8±10.9 46.8±12.1 …

Hospital length
3.0 (2.5, 3.3 (2.6,
of stay, median …
4.0) 5.1)
days, (IQR)†

In-hospital 1.94
5/786 18/137
cardiac arrest, n (1.10–
(7.3) (13.1)
(%) 3.40)

1.62
Heart failure, n
205 (12.9) 62 (19.4) (1.19–
(%)
2.22)

2.35
Cardiogenic
106 (6.7) 46 (14.4) (1.62–
shock, n (%)
3.40)

2.14
Major bleeding,
149 (9.4) 58 (18.2) (1.54–
n (%)
2.98)

 Instrumented 89 (5.6) 28 (8.8) …

 
60 (3.8) 30 (9.4) …
Noninstrumented

2.29
All-cause
59 (3.7) 26 (8.1) (1.42–
mortality, n (%)
3.69)

2.05
Composite
332 (20.9) 112 (35.1) (1.58–
outcome,‡ n (%)
2.65)

Plus-minus values are mean±SD.

*Odds ratios are only applicable to binary

outcomes.

†Among the nondeceased patients.

‡Composite outcome: HF, cardiogenic shock,

major bleeding, or death.

After multivariate adjustment, there was no

significant association between anemia and
development of HF or cardiogenic shock (OR,
0.96; CI, 0.65–1.40 and OR, 1.43; CI, 0.93–2.2,
respectively) after pPCI in STEMI patients.
However, anemia both as a threshold (ie,
hemoglobin <120 g/L females, <130 g/L males)
and range of severity was independently
associated with increased rates of major
bleeding (OR, 1.78; CI, 1.25–2.56 and OR, 1.09;
CI, 1.04–1.14, respectively; Figure 3). Although
in-hospital mortality was not influenced by
baseline anemia after adjusting for various
cofounders (OR, 0.99; CI, 0.57–1.73), lower
hemoglobin levels remained independently
associated with the composite adverse
outcome (OR, 1.43; 95% CI, 1.06–1.93;
P=0.02). In a sensitivity analysis in which
propensity score adjustment was used, the
estimated effect of anemia on adverse
outcomes was similar (Table III in the Data
Supplement). The predictive accuracy of the
logistic regression model was assessed through
concordance statistic (C statistics) yielding
strong performance across the selected
adverse outcomes (Table IV in the Data
Supplement).

Download figure | Download PowerPoint

Caption $

Reperfusion Times
Among STEMI patients receiving pPCI and
presenting directly to a PCI-capable hospital,
there was no significant difference in median
reperfusion times between anemic and
nonanemic patients (97 versus 95 minutes;
P=0.772). There was a delay in FMC-to-device
time in anemic STEMI patients transferred from
PCI noncapable hospitals compared with those
without anemia (median reperfusion time 140
versus 125 minutes; P=0.048). After adjustment
for age and sex, the presence of baseline
anemia did not affect reperfusion times overall
or in the PCI-capable hospitals. However, lower
hemoglobin levels were again associated with a
longer FMC-to-device time in STEMI patients
presenting to PCI noncapable hospitals
(rs=−0.14; P=0.002; Figure 4).