Washington University Emergency Medicine Journal Club – April 2024
This month’s journal club will look at the use of restrictive blood transfusion (Hgb < 7 to 8 g/dL) vs more liberal transfusion strategies (threshold Hgb < 10 g/dL) in patients with acute myocardial infarction. Given recent low attendance, I am making a plea to all to please try your best to attend while we consider changes to try and improve engagement.
The PGY-1, PGY-2, and PGY-3 papers will be appraised using the Therapy form, while the PGY-4 paper will be appraised using the Meta-Analysis form.
Vignette
You’re working a shift on community medicine rotation in a medium-sized
community-based ED one afternoon when you encounter Mr. S, a 62-year-old male
here visiting his son from Florida, with a history of hypertension, hyperlipidemia,
chronic iron-deficiency anemia, and coronary artery disease with a stent to his RCA
ten years previously. He presents now with substernal chest heaviness that began
while climbing the stairs at his son’s home and has persistent since. He took three
sublingual nitroglycerin tablets with some relief, but is currently having 3/10
discomfort. He is not short of breath or diaphoretic. His physical exam is
unremarkable.
The patient’s ECG reveals sinus rhythm with very mild ST depression in the anterior
leads and normal T-waves. You have no old records in your system for comparison.
After one additional sublingual nitro he is now pain free. His labs begin coming back
and reveal a high-sensitivity troponin T of 250 ng/L and a hemoglobin of 8.4 g/dL
with a microcytic pattern. You go back and ask the patient about recent bloody
stools or melena, both of which he denies.
After giving the patient an appropriate dose of aspirin and starting him on a heparin
drip for a non-ST elevation MI, you contact the on-call cardiologist with plans to
admit to the hospitalist. The cardiologist agrees with the plan but given the patient’s
obvious myocardial infarction she suggests you transfuse the patient up to a
hemoglobin of 10 g/dL. When you ask your attending, you are told this is not
necessary and that there is prior evidence that restrictive transfusion strategies are
just as efficacious (even in the setting of an acute MI), citing a prior journal club on
this topic. You successfully admit the patient to the hospitalist without a transfusion
but wonder what the evidence showed and if there has been any additional evidence
published in the interim. After your shift, you decide to dive into the literature and
see what the evidence shows…
PICO Question
Population: Adult patients with anemia with active or recent myocardial infarction
Intervention: Transfusion based on a restrictive strategy with lower threshold
hemoglobin levels (≤ 7 g/dL, ≤ 8 g/dL)
Comparison: Transfusion based on a liberal strategy with higher threshold
hemoglobin levels (≤ 9 g/dL, ≤ 10 g/dL)
Outcome: Mortality, myocardial infarction, need for unscheduled revascularization,
stroke, number of units of blood transfused, adverse transfusion reactions, clinically
significant volume overload, need for mechanical ventilation
Search Strategy
PubMed was searched using terms “anemia AND transfusion AND (“myocardial
infarction” or MI)” with results limited to “Clinical Trial,” “Meta-Analysis,” and
“Systematic Review.” (https://tinyurl.com/tkjpd9ce). This resulted in 127 citations,
from which the four most relevant were chosen.
Article 1: Carson JL, Brooks MM, Abbott JD, et al. Liberal versus restrictive
transfusion thresholds for patients with symptomatic coronary artery disease. Am
Heart J. 2013 Jun;165(6):964-971.e1. [Answer Key]
Article 2: Carson JL, Brooks MM, Hé bert PC, et al; MINT Investigators. Restrictive or
Liberal Transfusion Strategy in Myocardial Infarction and Anemia. N Engl J Med.
2023 Dec 28;389(26):2446-2456. [Answer Key]
Article 3: Ducrocq G, Gonzalez-Juanatey JR, Puymirat E, et al; REALITY Investigators.
Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular
Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY
Randomized Clinical Trial. JAMA. 2021 Feb 9;325(6):552-560. [Answer Key]
Article 4: Zhang Y, Xu Z, Huang Y, et al. Restrictive vs. Liberal Red Blood Cell
Transfusion Strategy in Patients With Acute Myocardial Infarction and Anemia: A
Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2021 Nov
16;8:736163. [Answer Key]
Bottom Line
While current guidelines—including those from the American Association of Blood
Banks, the American Association of Family Physicians, and the joint task force of EAST
(Eastern Association for Surgery of Trauma) and the American College of Critical Care
Medicine of the Society of Critical Care Medicine—recommend a restrictive blood
transfusion strategy for most patients, there are specific patient populations whose
physiology may affect such transfusion decisions. In patients with acute myocardial
infarction (AMI), for example, maintenance of circulating blood volume at higher levels
should theoretically improve oxygen delivery to already compromised cardiac tissue. We
sought to review articles comparing a liberal transfusion strategy (hemoglobin threshold
< 8 or 10 g/dL) with a more restrictive strategy (hemoglobin threshold < 7 g/dL) in
patients with anemia and AMI.
An initial pilot randomized controlled trial conducted at 8 centers in the US compared
liberal versus restrictive transfusion strategies for patients with acute coronary syndrome
(ST-segment elevation myocardial infarction [STEMI], non-ST segment elevation
myocardial infarction [NSTEMI], unstable angina, or stable coronary artery disease
undergoing cardiac catheterization). While there was a strong trend toward fewer major
adverse cardiac events (all-cause mortality, myocardial infarction, or unscheduled
revascularization within 30 days) with a risk difference (RD) of 15% (95% CI 0.7 to
29.3), this was a small (n = 110) pilot study whose results are not definitive.
The subsequent MINT trial, conducted based on the findings of this pilot study, enrolled
3506 patients with anemia who were having either an NSTEMI or STEMI. The primary
outcome—a composite of myocardial infarction or death at 30 days—occurred with
slightly higher frequency in the restrictive group compared to the liberal group: 16.9% vs.
14.5%, unadjusted risk ratio 1.16 (95% CI 1.00 to 1.35), although this did not quite
achieve statistical significance. There was also no statistically significant difference in the
rates of death (RR 1.19, 95% CI 0.96 to 1.47) or MI (RR 1.19, 95% CI 0.94 to 1.49) at 30
days, though there were trends toward improved outcomes with a liberal transfusion
strategy. While the authors conclude that “a liberal transfusion strategy did not
significantly reduce the risk of recurrent myocardial infarction or death at 30 days,” the
clear trend toward improved outcomes leaves the answer unclear.
In a second large RCT composed of 666 patients from 35 European centers (the
REALITY trial), there was a trend toward decreased incidence of major adverse cardiac
events in the restrictive versus the liberal transfusion group (relative risk [RR] 0.78, 1-
sided 97.5% CI 0.00 to 1.17). As this was a non-inferioty study and the upper limits of
the confidence interval did not cross the pre-specified non-inferiority threshold of 1.2, a
restrictive strategy was deemed noninferior to a liberal strategy. Almost all of the patients
in the liberal transfusion group received at least one unit of blood while only 35.7% of
those in the restrictive group received any blood. There were also higher incidences of
acute lung injury/ARDS, multiorgan system dysfunction, and infection in the liberal
transfusion group, although these events were fairly rare.
A systematic review and meta-analysis was also identified which predated the MINT
trial. This review included 6 studies comprising 6630 total patients; three of these studies
were RCTs, one was a prospective observational studies, and two were retrospective
observational studies. There was no statistically significant difference in mortality
between the restrictive and liberal transfusion groups (RR, 1.07, 95% CI = 0.82–1.40; I2
= 66%) and no difference in follow-up mortality (RR, 0.89, 95% CI = 0.56–1.42; I2 =
50%); restrictive transfusion was associated with a slightly higher risk of in-hospital
mortality compared with liberal transfusion (RR, 1.22, 95% CI = 1.00–1.50; I2 = 41%).
Unfortunately, the current body literature fails to provide a definitive answer to this
clinical conundrum. The two largest randomized controlled trials, REALITY and MINT,
provide conflicting results, with the former favoring restrictive transfusion and the latter
favoring liberal transfusion (though statistical significance was not quite achieved).
Clinicians should continue using their best judgement when managing anemia in patients
with AMI, taking into account concomitant heart failure and renal failure, the risk of
volume overload, and local blood bank availability.