Recombinant Factor VII Is Associated With Worse Survival in Complex Cardiac Surgical Patients

Abstract

Background Recombinant, activated factor VII(rFVIIa) decreases requirements for allogenic blood transfusion and chest re-exploration in cardiac surgical patients. Whether rFVIIa increases risk for postoperative adverse events is unclear. We tested whether rFVIIa administration was associated with increased mortality, neurologic and renal morbidity in cardiac surgical patients. Risk of thromboembolic complications and the dose-response of rFVIIa on mortality and morbidity was also evaluated. Methods Of 27,977 patients who had complex cardiac surgery, 164 patients(0.59%) received rFVIIa perioperatively. Using propensity-matching techniques, patients were matched to a maximum of 3 controls. Patients who received rFVIIa were compared with controls on risk of mortality, neurologic and renal morbidity and thromboembolic complications, including a composite of myocardial infarction, pulmonary embolism, and deep venous thrombosis. A corresponding “dose-response” analysis using multivariable logistic regression was also performed. Results Propensity techniques successfully matched 144 patients(88%) with 359 controls. Of patients who received rFVIIa, 40% experienced in-hospital mortality compared to 18% of controls(OR 2.82(1.64, 4.87);P<0.001). Furthermore, 31% of patients treated with rFVIIa vs 17% of controls experienced renal morbidity(OR 2.07(1.19, 3.62);P=0.002), however neurologic morbidity and thromboembolic complications were not different among groups. High-dose(>60mcg/kg) did not increase risk for mortality compared to treatment with low-dose rFVIIa(<60mcg/kg). Conclusion Administration of rFVIIa is associated with increased mortality and renal morbidity in cardiac surgery patients.

Analysis of Outcomes Using Low-Dose and Early Administration of Recombinant Activated Factor VII in Cardiac Surgery

“…Off-label use of rFVIIa for perioperative cardiac surgical bleeding was shown in previous studies to reduce both bleeding [3,4] and the rate of reoperations [4,5]. However, use of rFVIIa for cardiac surgical bleeding was shown to be associated with increased mortality [6], stroke [5,7,8], and renal morbidity [6]. Compared with the dosing strategy of the present study, previous studies used substantially larger doses of rFVIIa, which may have contributed to adverse events.…”

“…This approach is contrary to that of many centers, where rFVIIa for cardiac surgical bleeding is administered based on the dosing recommendations for patients with hemophilia of 90 mcg/kg. This dosing regimen and higher doses are used in many reports [3,6,[9][10][11][12]. Even recent reports suggesting the use of "lower-dose" rFVIIa have used doses three to four times those of the median dose received by patients in the current study [4,13].…”

Incidence of Venous Thromboembolism and Benefits and Risks of Thromboprophylaxis After Cardiac Surgery: A Systematic Review and Meta‐Analysis

“…The majority of the studies were observational studies (n=49), 16 studies were RCTs, and 3 were meta‐analyses (Tables 1 and 2). 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84 Of the 16 RCTs identified,1...…”

Management of severe perioperative bleeding

“…231 In an observational case control study with patients who received rFVIIa (n ¼ 144) intraoperatively or postoperatively and matched controls (n ¼ 359), the in-hospital mortality was 40% in the group receiving rFVIIa and 18% in the control group. 232 Renal morbidity was also increased in the group receiving rFVIIa (31 versus 17%, respectively).…”