Abstract Body (Do not enter title and authors here): Hypothesis and Purpose: The primary objective of the Transfusion Trigger after Operations in High Cardiac Risk Patients (TOP) trial was to determine whether a liberal postoperative transfusion strategy (hemoglobin [Hb] threshold <10 g/dL) reduces the risk of a 90-day composite endpoint compared to a restrictive strategy (Hb threshold <7 g/dL) in high cardiac-risk general and vascular surgery patients undergoing major operations. The hypothesis was that the liberal strategy will be superior to the restrictive strategy.

Study Design and Methods: Randomized controlled trial

Sample Size: 1520

Population Studied: The TOP trial enrolled adult veterans with a history of ischemic heart disease, stroke, or peripheral arterial disease undergoing major general or vascular surgery operations with postoperative Hb <10 g/dL within 15 days of the index surgery.

Intervention(s): In the liberal arm, transfusion was administered at a rate of one unit red blood cells (RBC) if initial Hb was > 8.5 g/dL, two units of RBC if Hb was <8.5 g/dL but >7.5 g/dL, and three units of RBC if Hb was <7.5 g/dL. In the restrictive arm, transfusion was required at a rate of one unit RBC if Hb was <7 g/dL but > 5.5 g/dL, and two units of RBC if Hb <5.5 g/dL. Subsequent transfusion decisions were made based on return Hb after each block of transfusions until discharge or 30 days.

Power Calculations: We determined that 1520 randomized participants were needed to detect a 25% difference in the primary endpoint with 90% power, and a two-sided test with an alpha level of 0.05. We assumed a composite endpoint incidence of 22.5% in the liberal arm and 30% in the restrictive arm.

Primary End Points: The primary endpoint was a composite of all-cause mortality, myocardial infarction, coronary revascularization, acute renal failure, or ischemic stroke assessed at 90 days after randomization.

Secondary End Points: Secondary endpoints were infectious complications (surgical site infections, pneumonia, sepsis), cardiac complications (new cardiac arrhythmias, new or worsening congestive heart failure, and cardiac arrest) at 90 days after randomization.

Outcome(s)[Statistical Plan]: Primary analyses were performed using the intention-to-treat principle. Pearson’s chi-squared test was used to compare the primary endpoint between transfusion strategies. Additional analyses were performed using logistic regression models to adjust for age, revised cardiac risk index, and nadir postoperative hemoglobin.