Association of Anemia and Transfusion with Major Adverse Cardiac Events and Major Adverse Limb Events in Patients Undergoing Open Infrainguinal Bypass

Abstract

Anemia is highly prevalent patients with peripheral vascular disease and has been associated with postoperative cardiac events and mortality, and adverse limb events after revascularization procedures. Allogenic blood transfusions have also been associated with adverse events including hospital acquired infections, cardiac morbidity and reduced survival. The aim of this study was to evaluate the impact of blood transfusion on major adverse cardiac events (MACE) and major adverse limb events (MALE) in patients undergoing infrainguinal lower extremity bypass operations. We performed a retrospective cohort analysis of patients undergoing infrainguinal lower extremity bypass in the Society for Vascular Surgery Vascular Quality Initiative database between 2003 and 2020. Patients were first grouped by their preoperative hemoglobin (Hgb) number (severe anemia: Hgb 7-10g/dL; moderate anemia: 10-12g/dL; normal Hgb: >12g/dL) and then stratified by their transfusion status (perioperative transfusion vs. no perioperative transfusion). Primary endpoints were MACE, defined as myocardial infarction, new congestive heart failure, dysrhythmia, or stroke in the postoperative period, and MALE, defined as return to operating room for thrombosis, loss of primary patency on follow-up and major ipsilateral amputation on follow-up. Secondary outcomes included wound complications, graft infections, 30-day mortality and 1-year survival. Outcomes were compared between patients who received transfusions and those who did not at every anemic threshold. Multivariable logistic regression was performed to evaluate the impact of blood transfusion on primary outcomes. A total of 55,884 patients were included for analysis, of which 16.3% had severe anemia, 25.9% had moderate anemia and 57.8% had normal hemoglobin. Anemia severity was associated with increased rates of MACE (9.8% vs. 8.3% vs. 5.2%, p<0.0001) and MALE (32.2% vs. 24.8% vs. 18.6%, p<0.0001). On univariate analysis, transfusion was consistently associated with increased rates of MACE and MALE at every anemic threshold (p<0.0001 for all). Transfusion was also associated with increased rates of 30-day mortality at all anemic thresholds (p<0.0001 for all) and reduced 1-year survival at all anemic thresholds (log-rank p<0.0001 for all). On multivariable analysis for MACE, an interaction factor was observed between preoperative Hgb and transfusion status (p<0.0001). At every anemic threshold, transfusion was independently associated with MACE (severe: OR 2.4 [95% CI: 2.0 - 2.9]; moderate: OR 2.8 [95% CI: 2.5 - 3.2]; normal: OR 4.5 [95% CI: 4.0 - 5.0]). On multivariable analysis for MALE, an interaction factor was also observed between preoperative Hgb and transfusion status (p<0.0001). At every anemic threshold, transfusion was independently associated with MALE (severe: OR 2.1 [95% CI: 1.9 - 2.3]; moderate: OR 1.8 [95% CI: 1.7 - 2.0]; normal: OR 2.6 [95% CI: 2.4 - 2.8]). Perioperative blood transfusion in patients undergoing infrainguinal lower extremity bypass is independently associated with MACE and MALE in all patients with preoperative Hgb > 7 g/dL. Despite the morbidities associated with anemia, these findings highlight that transfusion may not be the optimal treatment modality, particularly in patients with higher preoperative Hgb. Future research is needed to define the transfusion threshold in this population.