Decreasing Postoperative Blood Loss by Topical Versus Intravenous Tranexamic Acid in Open Cardiac Surgery - DEPOSITION

Apr 08, 2024
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Anthony A. Bavry, MD, MPH, FACC
Trial Sponsor:
Canadian Institutes of Health Research, and the Population Health Research Institute
Date Presented:
04/08/2024
Date Published:
04/08/2024
Original Posted Date:
04/08/2024
References

Contribution To Literature:

In patients undergoing open cardiac surgery on CPB in the DEPOSITION trial, topical intraoperative TXA did not reduce seizure incidence but was associated with increased RBC transfusion requirement compared with intravenous TXA.

Description:

The goal of the trial was to assess the safety and efficacy of topically administered tranexamic acid (TXA) with respect to postoperative seizure risk and need for red blood cell (RBC) transfusion, respectively, compared with intravenous TXA in open cardiac surgery.

Study Design

  • Randomized
  • Double-dummy
  • International multicenter

Patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) were randomized in a 1:1 fashion to receive intravenous or topical intraoperative TXA. Each patient was administered up to 5 grams of intravenous TXA (n = 1,624) or placebo once at case start and again intraoperatively as well as up to 10 grams of topical TXA (n = 1,618) or placebo delivered to the chest cavity prior to closing.

  • Total number of enrollees: 3,242
  • Duration of follow-up: hospital discharge or 10 days, whichever occurred sooner
  • Mean patient age: 66 years
  • Percentage female: 22%

Inclusion criteria:

  • Age ≥18 years
  • Undergoing cardiac surgery on CPB via median sternotomy

Exclusion criteria:

  • Minimally invasive cardiac surgery or pericardiectomy
  • Increased transfusion risk: emergent surgery, known bleeding disorder, inherited thrombophilic or hemorrhagic disease, or infective endocarditis
  • Prior cardiac surgery
  • Estimated glomerular filtration rate <30 mL/min/1.73 m2
  • Preoperative hemoglobin >17 or <11 g/dL
  • Preoperative platelet count <50,000 per µL
  • Anticipated intraoperative circulatory arrest

Other salient features/characteristics:

  • Elective surgery: 64%
  • Isolated coronary artery bypass grafting: 70%
  • Isolated valve surgery: 13%
  • Mean CPB time: 89 minutes
  • Mean aortic cross-clamp time: 66 minutes
  • Median intravenous TXA dose: 45 mg/kg
  • Median topical TXA dose: 71 mg/kg

Principal Findings:

The trial was stopped early following its second prespecified review (at 75% anticipated enrollment) by the Data and Safety Monitoring Board, which recommended stopping the trial for safety.

The primary outcome, seizure without new neurologic deficit or structural change, for topical vs. intravenous TXA, was: 0.2% vs. 0.7%, relative risk (RR) 0.36 (95% confidence interval [CI] 0.12-1.14), p = 0.07.

The secondary outcome, RBC transfusion, for topical vs. intravenous TXA, was: 35.1% vs. 26.8%, RR 1.31 (95% CI 1.18-1.46), p2-sided < 0.001, pnoninferiority = 0.007.

Tertiary outcomes for topical vs. intravenous TXA:

  • Any blood product transfusion: 46.6% vs. 36.0%, absolute risk difference (ARD) +10.6 (95% CI +7.2 to +13.9), p < 0.001
  • All-cause death, myocardial infarction, or stroke: 2.5% vs. 1.9%, ARD +0.6 (95% CI -0.5 to +1.6), p = 0.29

Post hoc tertiary outcomes of interest for topical vs. intravenous TXA:

  • Any seizure (including with new deficit or stroke): 0.2% vs. 0.9%, ARD -0.7 (95% CI -1.1 to -0.1), p = 0.02
  • ≥4 RBC units transfused: 22.5% vs. 14.3%, ARD +8.2 (95% CI +3.4 to +12.9), p < 0.001

Interpretation:

Perioperative hemorrhage is an important complication of cardiac surgery and is exacerbated by CPB, which triggers systemic inflammation and associated coagulopathy. Topical TXA administered directly to the surgical site has been proposed as a potential alternative to intravenous administration, which, though indicated to minimize surgical bleeding, results in higher systemic TXA levels and carries a small but dose-dependent risk of seizures.

The DEPOSITION trial represents the largest randomized sample to date of topical versus intravenous TXA in cardiac surgery and was terminated early due to a concerning signal for harm vis-à-vis increased RBC transfusion requirement. A completed trial may have provided enough power to definitively assess for a potential neurologic benefit. However, the overall primary event rate was much lower than the clinically significant differences in bleeding, especially severe hemorrhage requiring ≥4 RBC units, between treatment arms. The current data therefore do not support and in fact oppose routine use of topical overall intravenous TXA to control perioperative bleeding in cardiac surgery.

References:

Lamy A, Sirota DA, Jacques F, et al. Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial. Circulation 2024;Apr 8:[Epub ahead of print].

Presented by Dr. Andre Lamy at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 8, 2024.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention

Keywords: ACC24, ACC Annual Scientific Session, Cardiac Surgical Procedures, Tranexamic Acid


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