Abstract Body (Do not enter title and authors here): Introduction: Anemia has been shown to contribute to adverse outcomes in individuals with cardiovascular disease (CVD), including acute coronary syndromes (ACS). Our 2018 meta-analysis of 11 transfusion trigger trials suggested significant harm was associated with a restrictive red blood cell (RBC) transfusion trigger (hemoglobin 7-8 g/dl) vs. a liberal strategy (>10 g/dl) in subjects with CVD. Nevertheless, RBC transfusion guidelines as recently as 2023 have recommended “a threshold of 8g/dL for patients undergoing orthopedic surgery or those with pre-existing CVD.” Here we updated our meta-analysis.

Research Question/Hypothesis: Does CVD increase risks of a restrictive RBC transfusion strategy?
Methods/Approach: This update was registered in PROSPERO. The 2018 search was repeated Nov. 20, 2023. We excluded cardiac surgery studies because in a secondary analysis, the trial with the largest number of such subjects showed the effect on mortality of a liberal vs. restrictive RBC trigger was significantly different and opposite depending on the age of the subject (qualitative interaction, p=0.004). The most up-to-date results were used if follow-up studies for a trial were done.

Results/Data: Three new randomized RBC transfusion trigger trials enrolling 4,222 subjects with CVD met enrollment criteria. This brought the number of studies enrolling subjects with CVD not undergoing cardiac surgery hospitalized for non-cardiac reasons or ACS to 14. We found there were 334 deaths in the 3,211 subjects with CVD in the liberal arms (10.4% mortality) and 398 deaths in the 3,212 subjects in the restrictive arms (12.4%) [RR = 0.87, 95% CI (0.76-0.99), p=0.03, I²=0%]. We found for ACS, the estimated event rate is 244 out of 2,908 in the liberal arms (8.4%), and 309 out of 2941 in the restrictive arms (10.5%) [RR = 0.82, 95% CI (0.70-0.96), p=0.01, I²=0%].

Conclusions: This meta-analysis shows that CVD is associated with an increased risk of new onset ACS and death if a restrictive vs. a more liberal RBC transfusion strategy is employed. Furthermore, for cardiac surgery patients, age may be a critical factor in the decision to transfuse blood. Guidelines should be updated to better reflect these most recent findings. Rather than relying on a single number, the presence of cardiovascular comorbidities and other individual-dependent clinical factors such as age and the type of surgery being done may be more important factors to consider in deciding if to transfuse RBCs.