Transfusion Thresholds Square Off in Acute Myocardial Infarction

PHILADELPHIA — For acute myocardial infarction (MI) patients with anemia, being more liberal with blood transfusion thresholds didn’t significantly impact risk of recurrent heart attack or death in the MINT trial, although trends signaled some advantage.

Consideration of transfusion only once hemoglobin levels dropped below 8 g/dL carried a nonsignificant 15% greater relative risk of recurrent MI or death within 30 days compared with transfusion for everyone below 10 g/dL (16.9% vs 14.5%, risk ratio 1.15, P=0.07), reported Jeffrey L. Carson, MD, of Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey.

Mortality and MI both showed the same nonsignificant trend in favor of the restrictive strategy in the results presented at the American Heart Association meeting and published simultaneously in the New England Journal of Medicine.

The researchers pointed to the 95% confidence interval as containing values suggesting clinical benefit from the liberal but not restrictive transfusion strategy. “We think it’s a real finding,” Carson told MedPage Today. “There’s been such a push to using less blood. This will probably change the pendulum back a little bit.”

He concluded at the session that a liberal transfusion strategy “may be the most prudent approach” for anemic patients with MI.

At the very least, the trial rules out harm from a more liberal transfusion strategy in this population, which had been the concern, commented Dipti Itchhaporia, MD, of the University of California Irvine and a past president of the American College of Cardiology. “Now we know there’s no difference in terms of the strategies and that maybe there’s some clinically relevant benefit,” she told MedPage Today. “I think it’s going to allow a little bit more clinical judgment.”

The trial enrolled 3,504 adults with acute ST-segment elevation or non-ST-segment elevation myocardial infarction and a baseline hemoglobin level of less than 10 g/dL (mean 8.6) who were being treated at 144 sites in the U.S., Canada, France, Brazil, New Zealand, and Australia. Participants average age was 72.1, and 45.5% were women.

Randomized treatment was given open-label, which the researchers noted is typical for transfusion trials.

The restrictive transfusion protocol allowed, but did not require, transfusion when the hemoglobin level was less than 8 g/dL but strongly recommended it below 7 g/dL or when medication did not adequately control angina. The liberal transfusion protocol included one unit of packed red cells after randomization and then further transfusion to keep at or above 10 g/dL until the time of hospital discharge or 30 days. “Transfusion could be delayed in patients with volume overload until adequate diuresis or on the day of dialysis in patients with end-stage renal disease,” the researchers noted.

These differences yielded a 1.3 g/dL lower hemoglobin level on average in the restrictive-strategy group on day 1 after randomization and 1.6 g/dL lower level on day 3 of the average 5-day hospitalization. Liberal transfusion led to 3.5-fold more total units transfused, an average of 2.5 units per patient compared with 0.7 in the restrictive-strategy group.

Among the secondary endpoints, a composite endpoint used in prior trials, incorporating death, MI, ischemia-driven unscheduled coronary revascularization, or readmission to the hospital for an ischemic cardiac condition within 30 days, likewise numerically favored the more liberal strategy (19.6% vs 17.4%, RR 1.13, 95% CI 0.98-1.29).

Cardiac death came out significantly more common with the restrictive strategy (5.5% vs 3.2%, RR 1.74, 95% CI 1.26 to 2.40), but the researchers cautioned that this endpoint, while prespecified, was not even a tertiary outcome, was not adjudicated, and accounted for less than half the deaths overall.

Subgroup analysis pointed to a significant benefit for the primary, combined mortality and MI endpoint only in patients with type 1 MI (RR 1.32, 95% CI 1.04-1.67).

Late-breaking clinical trial session study discussant C. Michael Gibson, MD, of Harvard University in Boston, cautioned that there was no adjustment for multiple comparisons in secondary outcomes or subgroups and that there were no interaction terms given.

Another limitation was the moderate adherence to the 10 g/dL transfusion threshold in the liberal transfusion group (86.3% at hospital discharge), Gibson noted.

Transfusion-associated cardiac overload was significantly less common with the restrictive transfusion strategy (0.5% vs 1.3%) but heart failure events did not differ significantly, which the researchers called a “more comprehensive measure of volume overload.”

“Given lack of acute harm associated with liberal transfusion and the preponderance of evidence favoring liberal transfusion in the largest trial to date [MINT], liberal transfusion appears to be a viable management strategy, particularly among patients with NSTEMI type 1 MI and as clinical judgement dictates,” Gibson concluded.

AHA press conference study discussant Martin Leon, MD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York City, noted the number needed to treat of 40 for the primary endpoint. While the trial wasn’t quite a “home run,” he said, “I think it will be interpreted that the effect size is somewhat smallish but meaningful. And the liberal strategy will probably be the dominant strategy in most patient cohorts as the point estimates are very consistent.”

Disclosures

The trial was supported by grants from the National Heart, Lung, and Blood Institute and by the Canadian Blood Services and Canadian Institutes of Health Research Institute of Circulatory and Respiratory Health.

Carson disclosed relationships with Cerus and Johnson & Johnson Health Care Systems.

Gibson disclosed relationships with Janssen/Johnson & Johnson, CSL Behring, SCAD Alliance, Baim Institute, nference, Dyad Medical, Absolutys, Fortress Biotech, Angel/Avertix Medical, MD Magazine, AstraZeneca, Microdrop, Bayer, Microport, Boston Clinical Research Institute, Miracor, Bristol-Myers Squibb, MJ Health, Caladrius Biosciences, Novartis, Cardiovascular Research Foundation, Novo Nordisk, CeleCor Therapeutics, Pfizer, Cytokinetics, PLx Pharma, Daiichi Sankyo, Smart Medics, Esperion, EXCITE International, Somahlution/Marizyme, Vectura, Janssen/Johnson & Johnson, WebMD, MashUp MD, Woman As One, Angel/Avertix Medical, MD Magazine, AstraZeneca, Bayer, Microport, Boston Clinical Research Institute, Miracor, Caladrius Biosciences, Novartis, Pfizer, Cytokinetics, and Solstic Health/New Amsterdam Pharma.

Itchhaporia disclosed no relationships with industry.

Leon disclosed multiple relationships with industry including Abbott Vascular, Abiomed, Arintra, BackBeat Medical, Boston Scientific (Sadra & Claret), Caliber Therapeutics, Conveyor Cardiovascular, Siemens (Corindus Vascular Robotics), Edwards Lifesciences, East End Medical LLC, Cardiovascular Systems Inc. (CSI, Wirion System), Elixir Medical, Gore Medical, Ancora, Medtronic, Mitraltech Cardiovalve, SoniVie, TriReme Medical, CathWorks (Triventures), Corvia, Venus MedTech, Hawthorne Effect, Impulse Dynamics, OrbusNeich, V-Wave (Triventures), Vascular Imaging, Vivasure Medical, K2 Medical, Medinol (Valve Medical), Bain Capital, and Heart Leaflet Technologies.

Primary Source

New England Journal of Medicine

Source Reference: Carson JL, et al “Restrictive or liberal transfusion strategy in myocardial infarction and anemia” N Engl J Med 2023; DOI: 10.1056/NEJMoa2307983.

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