Washington University Emergency Medicine Journal Club- April 2024
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, Chaitman B, Kelsey SF, Triulzi DJ, Srinivas V, Menegus MA, Marroquin OC, Rao SV, Noveck H, Passano E, Hardison RM, Smitherman T, Vagaonescu T, Wimmer NJ, Williams DO. Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease. Am Heart J. 2013 Jun;165(6):964-971.e1. doi: 10.1016/j.ahj.2013.03.001. Epub 2013 Apr 8. PMID: 23708168; PMCID: PMC3664840. Answer Key
Article 2: Carson JL, Brooks MM, Hébert PC, Goodman SG, Bertolet M, Glynn SA, Chaitman BR, Simon T, Lopes RD, Goldsweig AM, DeFilippis AP, Abbott JD, Potter BJ, Carrier FM, Rao SV, Cooper HA, Ghafghazi S, Fergusson DA, Kostis WJ, Noveck H, Kim S, Tessalee M, Ducrocq G, de Barros E Silva PGM, Triulzi DJ, Alsweiler C, Menegus MA, Neary JD, Uhl L, Strom JB, Fordyce CB, Ferrari E, Silvain J, Wood FO, Daneault B, Polonsky TS, Senaratne M, Puymirat E, Bouleti C, Lattuca B, White HD, Kelsey SF, Steg PG, Alexander JH; MINT Investigators. Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia. N Engl J Med. 2023 Dec 28;389(26):2446-2456. doi: 10.1056/NEJMoa2307983. Epub 2023 Nov 11. PMID: 37952133; PMCID: PMC10837004. Answer Key.
Article 3: Ducrocq G, Gonzalez-Juanatey JR, Puymirat E, Lemesle G, Cachanado M, Durand-Zaleski I, Arnaiz JA, Martínez-Sellés M, Silvain J, Ariza-Solé A, Ferrari E, Calvo G, Danchin N, Avendaño-Solá C, Frenkiel J, Rousseau A, Vicaut E, Simon T, Steg PG; 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. doi: 10.1001/jama.2021.0135. PMID: 33560322; PMCID: PMC7873781. Answer Key.
Article 4: Zhang Y, Xu Z, Huang Y, Ye Q, Xie N, Zeng L, Lian X, Dai Y, Chen J, He P, Tan N, Liu Y. 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. doi: 10.3389/fcvm.2021.736163. PMID: 34869640; PMCID: PMC8636896. 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.