Fish Oil and Perioperative Bleeding Insights From the OPERA Randomized Trial

BACKGROUND: Fish oil is among the most common natural supplements for treatment of hypertriglyceridemia or prevention of cardiovascular disease. However, concerns about theoretical bleeding risk have led to recommendations that patients should stop taking fish oil before surgery or delay in elective procedures for patients taking fish oil by some health care professionals. METHODS AND RESULTS: We tested the effect of fish oil supplementation on perioperative bleeding in a multinational, placebo-controlled trial involving 1516 patients who were randomized to perioperative fish oil (eicosapentaenoic acid+docosahexaenoic acid; 8-10 g for 2-5 days preoperatively, and then 2 g/d postoperatively) or placebo. Primary outcome was major perioperative bleeding as defined by the Bleeding Academic Research Consortium. Secondary outcomes include perioperative bleeding per thrombolysis in myocardial infarction and International Society on Thrombosis and Hemostasis definitions, chest tube output, and total units of blood transfused. Participants' mean (SD) age was 63 (13) years, and planned surgery included coronary artery bypass graft (52%) and valve surgery (50%). The primary outcome occurred in 92 patients (6.1%). Compared with placebo, risk of Bleeding Academic Research Consortium bleeding was not higher in the fish oil group: odds ratio, 0.81; 95% CI, 0.53-1.24; absolute risk difference, 1.1% lower (95% CI, -3.0% to 1.8%). Similar findings were seen for secondary bleeding definitions. The total units of blood transfused were significantly lower in the fish oil group compared with placebo (mean, 1.61 versus 1.92; k0.001). Evaluating achieved plasma phospholipid omega-3 polyunsaturated fatty acids levels with supplementation (on the morning of surgery), higher levels were associated with lower risk of Bleeding Academic Research Consortium bleeding, with substantially lower risk in the third (odds ratio, 0.30 [95% CI, 0.11-0.78]) and fourth (0.36 [95% CI, 0.15-0.87]) quartiles, compared with the lowest quartile. CONCLUSIONS: Fish oil supplementation did not increase perioperative bleeding and reduced the number of blood transfusions. Higher achieved n-3-PUFA levels were associated with lower risk of bleeding. These novel findings support the need for reconsideration of current recommendations to stop fish oil or delay procedures before cardiac surgery.