Literature Scan
New and noteworthy research from the
medical literature landscape
Restrictive Transfusion Therapy Safe for
Cardiac Surgery Patients
Setting higher hemoglobin (Hb)
thresholds for red-cell transfusion
therapy in patients undergoing
cardiac surgery with a moder-
ate to high risk of death was
noninferior to using traditional
thresholds in reducing the risk
of death, myocardial infarction
(MI), stroke, and new-onset renal
failure at six months, according
to results from a study published
in the New England Journal of
Medicine.
“[Our results] show that a
restrictive transfusion policy can
safely be used and accordingly
reduces the unnecessary exposure
of patients to blood products and
risks secondary to transfusion,
which range from mild to life
threatening,” principal investiga-
tor Nadine Shehata, MD, of the
University of Toronto, told ASH
Clinical News.
This report updates previ-
ous research from the random-
ized, noninferiority Transfusion
Requirements in Cardiac
Surgery (TRICS) III trial, which
“A restrictive
transfusion
policy ...
reduces the
unnecessary
exposure
of patients
to blood
products
and risks
secondary to
transfusion.”
—NADINE SHEHATA, MD
22
ASH Clinical News
demonstrated that a restrictive
strategy (transfusion threshold of
Hb <7.5 g/dL) was noninferior to
a liberal strategy (Hb <9.5 g/dL
intraoperatively or postoperatively
while in the intensive care unit
[ICU], or <8.5 g/dL when the
patient was in the non-ICU ward)
in terms of patient morbidity and
mortality at 28 days after cardiac
surgery.
The TRICS III trial included
5,243 patients who were sched-
uled to undergo cardiac surgery
and were at moderate to high risk
of death, defined as a European
System for Cardiac Operative
Risk Evaluation I score of ≥6.
People who were unable to receive
blood products, declined blood
products, were participating in
a preoperative autologous blood
donation program, were under-
going heart transplantation, or
were having surgery solely for the
insertion of a ventricular assist
device were excluded from the
analysis.
This primary per-protocol
analysis included 4,860 partici-
pants who were assigned to either
a restrictive transfusion strategy
(n=2,430) or a liberal transfu-
sion strategy (n=2,430). The
primary composite outcome at
six months included the following
components:
• death from any cause
• myocardial infarction
• new focal neurologic deficit
(stroke)
• new-onset renal failure with
dialysis
A secondary composite outcome
included these factors, as well
as emergency department visit,
hospital readmission, or coronary
revascularization.
The primary outcome, for re-
strictive versus liberal transfusion
strategies, was 11.4 percent versus
12.5 percent (odds ratio [OR] =
0.90; 95% CI 0.76-1.07; p<0.001
for noninferiority).
At six months postsurgery, the
primary composite outcome was
observed in 402 patients in the
liberal threshold group and 402
patients in the restrictive thresh-
old group (17.1% vs. 17.4%;
OR=1.02; 95% CI 0.87-1.18;
p=0.006 for noninferiority).
Mortality rates also were
similar between the groups: 6.4
percent for liberal threshold vs.
6.2 percent for restrictive thresh-
old (OR=0.95; 95% CI 0.75-1.21).
In addition, the investigators
observed no difference between
the two groups in terms of the
expanded secondary compos-
ite outcome (43.8% vs 42.8%;
OR=1.04; 95% CI 0.93-1.17; p
value not reported).
In a subgroup analysis, the in-
vestigators found that the restric-
tive strategy actually was superior
in patients aged ≥75 years, but
in patients aged <75 years, the
liberal strategy was associated
with a lower risk of the primary
composite outcome (p=0.004).
“The findings in patients 75
years of age or older appear to
contradict the current practice,
in which a liberal transfusion
strategy is used in older patients
undergoing cardiac or noncardiac
surgery who thus receive more
red-cell transfusions than do
younger patients,” the researchers
noted. “One could hypothesize
that older patients may have
unacceptable adverse effect re-
lated to transfusion (e.g., volume
overload and inflammatory and
infectious complications) or that
there may be age-related differ-
ences in the adverse-effect profile
of transfusion or anemia. … The
mechanisms underlying any po-
tential differential effect of age on
outcomes of transfusion must be
further studied within the cardiac
surgery population.”
Dr. Shehata also noted that
the study’s findings could have
implications for health-care
costs. “Transfusion is costly,
and although each unit of red
blood cells is approximately
$300 to $400 [in Canada],
this cost does not account for
nursing administration costs
and potential adverse events that
could prolong hospitalization,”
she stated. “Some estimate the
cost to be well over $1,000 per
unit when administration costs
are considered, so a restrictive
strategy would reduce those
costs.”
Adopting a restrictive strategy
also would alleviate some of the
strain on the nation’s blood supply.
“Donors are donating their blood
for patients needing life-saving
transfusions,” she added. “Using
higher thresholds for a transfusion
reduces the unnecessary use of
blood products, so that they can be
directed to those in need.”
The study’s findings were
limited by the lack of required
follow-up of patients after 28 days
or hospital discharge and the fact
that outcomes data were obtained
from a variety of sources (tele-
phone contact, databases, hospital
records), which increased the
odds that some follow-up visits
were missed.
“TRICS III was a large, multi-
center, international study with a
high adherence rate to transfusion
strategies, thus we believe our re-
sults are valid and generalizable,”
Dr. Shehata explained when asked
about the study’s strengths and
weaknesses. “The only potential
finding that likely merits additional
investigation is whether the age of
the patients should be a factor to
consider when transfusing cardiac
surgery patients.”
The authors report no conflicts
of interest. ●
REFERENCE
Mazer CD, Whitlock RP, Fergusson DA, et al. Six-month
outcomes after restrictive or liberal transfusion for cardiac
surgery. N Engl J Med. 2018;379:1224-33.
January 2019