Factor Eight Inhibitor Bypass Activity use in cardiac surgery: A propensity matched analysis of safety outcomes.

BACKGROUND: Bleeding during cardiac surgery may be refractory to standard interventions. Off-label use of Factor Eight Inhibitor Bypass Activity (FEIBA) has been described to treat such bleeding. However, reports of safety, particularly thromboembolic outcomes, show mixed results and reported cohorts have been small. METHODS: Adult patients undergoing cardiac surgery on cardiopulmonary bypass between July 1, 2018 and June 30, 2023 at Stanford Hospital were reviewed (n=3335). Patients who received FEIBA to treat post-cardiopulmonary bypass bleeding were matched with those who did not by propensity scores in a 1:1 ratio using nearest neighbor matching (n= 352 per group). The primary outcome was a composite outcome of thromboembolic complications including any one of deep vein thrombosis (DVT), pulmonary embolism (PE), unplanned coronary artery intervention, ischemic stroke, and acute limb ischemia, in the postoperative period. Secondary outcomes included renal failure, reoperation, postoperative transfusion, ICU length of stay (LOS), and 30-day mortality. RESULTS: 704 encounters were included in our propensity matched analysis. The mean dose of FEIBA administered was 7.3 ±5.5 units/kg. In propensity matched multivariate logistic regression models there was no statistically significant difference in odds ratios for thromboembolic outcomes, ICU LOS, or mortality. Patients who received >750 units of FEIBA had an increased odds ratio for acute renal failure (OR 4.14; 95% CI 1.61 to 10.36, p <0.001). In multivariate linear regression, patients receiving FEIBA were transfused more plasma and cryoprecipitate postoperatively. However, only the dose range of 501-750 units was associated with an increase in transfusion of RBCs (ß 2.73; 95% CI 0.68 to 4.78; p=0.009), and platelets (ß 1.74; 95% CI 0.85 to 2.63; p <0.001). CONCLUSIONS: Low dose FEIBA administration during cardiac surgery does not increase risk of thromboembolic events, ICU LOS, or mortality in a propensity matched cohort. Higher doses were associated with increased acute renal failure and postoperative transfusion. Further studies are required to establish the efficacy of activated factor concentrates to treat refractory bleeding during cardiac surgery.

Adequate enrollment of women in cardiovascular drug trials and the need for sex-specific assessment and reporting.

Cardiovascular disease (CVD) is the leading cause of death for women in the United States and globally. There is an abundance of evidence-based trials evaluating the efficacy of drug therapies to reduce morbidity and mortality in CVD. Additionally, there are well-established influences of sex, through a variety of mechanisms, on pharmacologic treatments in CVD. Despite this, the majority of drug trials are not powered to evaluate sex-specific outcomes, and much of the data that exists is gathered post hoc and through meta-analysis. The FDA established a committee in 1993 to increase the enrollment of women in clinical trials to improve this situation. Several authors, reviewing committees, and professional societies have highlighted the importance of sex-specific analysis and reporting. Despite these statements, there has not been a major improvement in representation or reporting. There are ongoing efforts to assess trial design, female representation on steering committees, and clinical trial processes to improve the representation of women. This review will describe the pharmacologic basis for the need for sex-specific assessment of cardiovascular drug therapies. It will also review the sex-specific reporting of landmark drug trials in hypertension, coronary artery disease (CAD), hyperlipidemia, and heart failure (HF). In reporting enrollment of women, several therapeutic areas like antihypertensives and newer anticoagulation trials fare better than therapeutics for HF and acute coronary syndromes. Further, drug trials and cardiometabolic or lifestyle intervention trials had a higher percentage of female participants than the device or procedural trials.