Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation Study

Abstract

Background In the PAUSE (Perioperative Anticoagulant Use for Surgery Evaluation) Study, a simple, standardized, perioperative interruption strategy was provided for patients with nonvalvular atrial fibrillation taking direct oral anticoagulants (DOACs). Our objective was to define the factors associated with perioperative bleeding. Methods and Results We analyzed bleeding as the composite of major and clinically relevant nonmajor bleeding. Putative predictors of bleeding, and preoperative DOAC level were prospectively collected during recruitment. We used stratified logistic regression models for analysis. All statistical analyses were performed in R version 3.6.0. There were 3007 patients requiring perioperative DOAC interruption. More than one third of the included patients underwent a high bleeding risk procedure. The 30‐day rates of major and clinically relevant nonmajor bleeding were 3.02% in apixaban (n=1257), 2.84% in dabigatran (n=668), and 4.16% for rivaroxaban (n=1082). Multivariate analysis stratified by region found more bleeding for hypertension (odds ratio [OR], 1.79; 95% CI 1.07‐2.99; P =0.027), and prior bleeding (OR, 1.71; 95% CI, 1.08‐2.71; P =0.021). Surgical bleed risk classification (high‐ versus low‐risk) as a predictor of bleeding was only significant in the univariate analysis. The prediction model for major and clinically relevant nonmajor bleeding had an area under the curve of 0.71, and the preoperative DOAC level did not improve the area under the curve of the model. Conclusions In patients treated with DOACs who required an elective surgery/procedure and were managed with standardized DOAC interruption and resumption, there we did not find reversible risk factors for bleeding, suggesting that adjustment of the PAUSE management protocol to mitigate against bleeding is not needed.

Pharmacokinetics of Direct Oral Anticoagulants in Emergency Situations: Results of the Prospective Observational RADOA-Registry

“…The results of our study are in contrast to the results of the PAUSE study, which demonstrated that the use of a standardized protocol to stop DOAC treatment before elective procedures resulted in residual DOAC levels below 30 ng/mL in more than 67% of patients and less than 5.3% were above 50 ng/mL. 24 In contrast, the wide range and high levels of DOAC concentrations observed in our registry are due to the life-threatening clinical situations in which the anticoagulants cannot be stopped in time. In these critical situations rapid and quantitative determination of DOAC concentrations seems to be essential to estimate the bleeding risk in these special patient populations.…”

Perioperative Considerations for Antithrombotic Therapy in Oculofacial Surgery: A Review of Current Evidence and Practice Guidelines

“… 27 , 67 In this study, hypertension was the only modifiable risk factor in predicting bleeding events. 67 …”

Recommendations from the ICM-VTE: General

“…A sub-analysis of patients in the PAUSE trial found that separating patients into residual levels of > 50 ng/mL or £ 50 ng/ mL did not result in significant association with major and nonmajor bleeding events, suggesting that checking residual drug levels prior to surgery does not help to predict bleeding events when drugs are stopped at the times used in the study 1800 .…”

“…Oberweis et al, reported that procedure type (Spinal surgery > THA > TKA), active cancer, female sex, CAD and chronic obstructive pulmonary disease (COPD) are independent risk factors for MBE 634 . Previous perioperative bleeding and active cancer are known as risk factors for MBE after surgical procedures 635,636 In a recent study, Tafur et al, found that hypertension is also a risk factor for perioperative bleeding 637 . In a systematic review performed by Borre et al, in a patient group with 322,010 patients, patients with chronic kidney disease are at increased risk for MBE (moderate strength of evidence) 638 .…”