Risk Factors For MACE And Bleeding In Atrial Fibrillation Patients Undergoing Surgery: Insights From The Bridge Trial.

INTRODUCTION: -Patients with atrial fibrillation (AF) undergoing elective procedures are at risk for Major Adverse Cardiovascular Events (MACE) and symptomatic bleeding. We aimed to identify risk factors to guide perioperative risk stratification. METHODS: -We conducted a post-hoc analysis of the "Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery" randomized trial. The primary outcomes were MACE and symptomatic bleeding. Our statistical approach encompassed standard univariate analysis, logistic stepwise regression, and Cox regression models. Additional interaction analyses evaluated the interplay between low-molecular-weight heparin bridge therapy and other identified risk factors. RESULTS: -Among A total of 1,813 participants (mean age 71.6±8.8, 73.3% male), MACE occurred in 25 (1.4%) individuals, with pre-procedure clopidogrel use (adjusted hazard ratio [aHR] 7.73, 95% CI 2.63-22.72, p<0.001) and CHA2DS2-VASc score ≥ 5 (aHR 2.89, 95% CI 1.26-6.63, p=0.012) identified as risk factors. Symptomatic bleeding occurred in 57 (3.1%) individuals, with bridge therapy (aHR 1.84, 95% CI 1.07-3.19, p=0.029), renal disease (aHR 2.50, 95% CI 1.34-4.67, p=0.004), post-procedure aspirin use (aHR 2.86, 95% CI 1.66-4.91, p<0.001), post-procedure nonsteroidal anti-inflammatory drug use excluding aspirin (aHR 3.40, 95% CI 1.22-9.43, p=0.019), and major surgery (aHR 3.94, 95% CI 2.26-6.85, p<0.001) identified as risk factors. The interactions between risk factors and bridging therapy on MACE and symptomatic bleeding outcomes were not significant (p>0.05). CONCLUSION: -We identified predictors for MACE and symptomatic bleeding in AF patients undergoing elective procedures. These insights may help guide perioperative decisions to reduce the risk of adverse outcomes.

Perioperative management and outcomes in patients receiving low-dose rivaroxaban and/or aspirin: a subanalysis of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial.

BACKGROUND: No study has investigated the perioperative management and clinical outcomes in patients who are receiving rivaroxaban 2.5 mg twice a day and acetylsalicylic acid (ASA) 81 to 100 mg daily. OBJECTIVE: To assess perioperative management and outcomes in patients who are receiving low-dose rivaroxaban, 2.5 mg twice-daily, and low-dose ASA, 81 to 100 mg daily. To assess perioperative management and outcomes in patients who are receiving low-dose rivaroxaban, 2.5 mg twice-daily, and low-dose ASA, 81 to 100 mg daily. METHODS: Subanalysis of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial was performed to assess perioperative management and clinical outcomes in patients with stable coronary or peripheral artery disease who were randomized to receive rivaroxaban 2.5 mg twice a day plus ASA 100 mg daily, rivaroxaban 5 mg twice a day, or ASA 100 mg daily. Patients studied required a surgery/procedure during the trial. The study outcomes, which included myocardial infarction, angina, stroke, acute limb ischemia, bleeding, and death, were assessed according to treatment allocation. RESULTS: There were 2632 patients studied (mean age, 68 years; 80% male) who had a surgery/procedure, comprising percutaneous coronary interventions (∼43%), carotid or other arterial angioplasty (∼15%), pacemaker or internal cardiac defibrillator implantation (∼9%), and coronary artery bypass graft surgery (∼7%). Perioperative study drug management varied, with about one-third of patients not interrupting study drug and the remainder interrupting it between 1 and ≥10 days preprocedure. The incidences of adverse outcomes across treatment groups were 12.7% to 15.3% for myocardial ischemia, 0.8% to 1.2% for stroke, 0.1% to 0.2% for venous thromboembolism, and 3.1% to 4.2% for any bleeding. There was no statistically significant difference in outcome rates across treatment groups. CONCLUSION: In patients in the COMPASS trial who required a surgery/procedure, there was no significant difference in perioperative adverse outcomes whether patients were receiving rivaroxaban 2.5 mg twice a day and ASA 100 mg daily, rivaroxaban 5 mg twice a day, or ASA alone.

Periprocedural management of direct oral anticoagulants in patients with atrial fibrillation and active cancer.

BACKGROUND: Cancer and atrial fibrillation (AF) are common concurrent disorders. Direct oral anticoagulants (DOACs) are prescribed to prevent stroke in patients with AF. Patients with cancer often undergo invasive procedures for diagnostic or therapeutic purposes, necessitating interruption of anticoagulation. There are limited data to guide best periprocedural anticoagulation management practices in the setting of active cancer. OBJECTIVES: To describe patient characteristics, periprocedural management, and clinical outcomes in DOAC-treated patients with AF according to active cancer status. METHODS: We conducted descriptive and comparative analyses using data from the PAUSE study. Multivariable logistic regression was used to determine whether active cancer status was an independent risk factor for bleeding outcomes. Covariates were selected a priori based on biological rationale and preexisting knowledge. RESULTS: Patients with active cancer were older (P < .001), more likely to be thrombocytopenic (P = .026), have moderate renal dysfunction (P = .005), and more likely to receive low-dose DOAC therapy (P < .001). A greater proportion of patients with active cancer underwent a high-bleed-risk procedure (P < .001), with longer periprocedural DOAC-interruption intervals (P <.001) and lower preprocedural residual DOAC levels (P = .002). Active cancer was an independent predictor for surgical major bleeding (OR = 2.45; 95% CI, 1.08-5.14) after adjusting for study center, procedure category and bleed risk, thrombocytopenia, hypertension, and the use of a P2Y12 inhibitor. CONCLUSIONS: Active cancer status is associated with an increased risk of surgical major bleeding among DOAC-treated patients with AF undergoing interruption of anticoagulation for elective invasive procedures.

Perioperative Management of Vitamin K Antagonists and Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.

BACKGROUND: The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario. RESEARCH QUESTION: What is the best available evidence to support the development of American College of Chest Physicians guidelines on the perioperative management of patients who are receiving long-term vitamin K agonist (VKA) or direct oral anticoagulant (DOAC) and require elective surgery or procedures? STUDY DESIGN AND METHODS: A literature search including multiple databases from database inception through July 16, 2020, was performed. Meta-analyses were conducted when appropriate. RESULTS: In patients receiving VKA (warfarin) undergoing elective noncardiac surgery, shorter (< 3 days) VKA interruption is associated with an increased risk of major bleeding. In patients who required VKA interruption, heparin bridging (mostly with low-molecular-weight heparin [LMWH]) was associated with a statistically significant increased risk of major bleed, representing a very low certainty of evidence (COE). Compared with DOAC interruption 1 to 4 days before surgery, continuing DOACs may be associated with higher risk of bleeding demonstrated in some, but not all studies. In patients who needed DOAC interruption, bridging with LMWH may be associated with a statistically significant increased risk of bleeding, representing a low COE. INTERPRETATION: The certainty in the evidence supporting the perioperative management of anticoagulants remains limited. No high-quality evidence exists to support the practice of heparin bridging during the interruption of VKA or DOAC therapy for an elective surgery or procedure, or for the practice of interrupting VKA therapy for minor procedures, including cardiac device implantation, or continuation of a DOAC vs short-term interruption of a DOAC in the perioperative period.

Perioperative Management of Anticoagulant and Antiplatelet Therapy.

Anticoagulant and Antiplatelet Drug ManagementManagement of patients on an anticoagulant or antiplatelet drug who require surgery or an invasive procedure is a common clinical problem. Douketis and Spyropoulos provide an evidence-based but practical approach to managing anticoagulants and antiplatelet drugs in the perioperative setting.

Coagulation assays and direct oral anticoagulant levels among patients having an elective surgery or procedure.

BACKGROUND: The Perioperative Anticoagulation Use for Surgery Evaluation study prospectively evaluated a prespecified periprocedural interruption strategy of direct oral anticoagulants (DOACs) among patients with atrial fibrillation. Coagulation testing is widely available and frequently requested prior to invasive procedures. Coagulation assays display poor sensitivity to clinically relevant DOAC concentrations. OBJECTIVES: Determine the utility of routinely available coagulation testing at predicting a DOAC concentration of <30 ng/ml among patients in the preprocedural setting. METHODS: We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratio (LR+ and LR-) of a normal coagulation assay result for identifying patients with a preprocedural DOAC level < 30 ng/ml. RESULTS: We identified weak or very weak correlations between coagulation assay results and DOAC levels in the preprocedural setting, except for a moderate correlation between the thrombin time (TT) and dabigatran concentrations (ρ = 0.68; p < .001). The prothrombin time (PT) and activated partial thromboplastin time (APTT) demonstrated modest sensitivity (78.9% to 88.2%) and PPVs (76.4% to 93.1%) but poor specificity (13.2% to 53.3%) and NPVs (16.3% to 30.2%) across all three DOACs. A normal TT was associated with 100% specificity and PPV values for a dabigatran level < 30 ng/ml. A normal APTT among patients on dabigatran was associated with an LR+ of 1.671 (95% confidence interval [CI] 1.297, 2.154) and an LR- of 0.395 (95% CI 0.207, 0.751) for levels <30 ng/ml. CONCLUSIONS: The PT and APTT perform poorly at safely identifying patients with negligible DOAC levels in the preprocedural setting.

Perioperative Management of Antiplatelet Therapy: A Systematic Review and Meta-analysis.

Objective: To summarize the available evidence about the perioperative management of patients who are receiving long-term antiplatelet therapy and require elective surgery/procedures. Methods: This systematic review supports the development of the American College of Chest Physicians guideline on the perioperative management of antiplatelet therapy. A literature search of MEDLINE, EMBASE, Scopus and Cochrane databases was conducted from each database's inception to July 16, 2020. Meta-analyses were conducted when possible. Results: In patients receiving long-term antiplatelet therapy and undergoing elective noncardiac surgery, the available evidence did not show a significant difference in major bleeding between a shorter vs longer antiplatelet interruption, with low certainty of evidence (COE). Compared with patients who received placebo perioperatively, aspirin continuation was associated with increased risk of major bleeding (relative risk [RR], 1.31; 95% CI, 1.15-1.50; high COE) and lower risk of major thromboembolism (RR, 0.74; 95% CI, 0.58-0.94; moderate COE). During antiplatelet interruption, bridging with low-molecular-weight heparin was associated with increased risk of major bleeding compared with no bridging (RR, 1.86; 95% CI, 1.24-2.79; very low COE). Continuation of antiplatelets during minor dental and ophthalmologic procedures was not associated with a statistically significant difference in the risk of major bleeding (very low COE). Conclusion: This systematic review summarizes the current evidence about the perioperative management of antiplatelet therapy and highlights the urgent need for further research, particularly with the increasing prevalence of patients taking 1 or more antiplatelet agents.

Executive Summary: Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline.

BACKGROUND: The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug. METHODS: Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines. RESULTS: A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures. CONCLUSIONS: Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions.

Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline.

BACKGROUND: The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug. METHODS: Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines. RESULTS: A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures. CONCLUSIONS: Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions.

Venous thromboembolism prophylaxis in high-risk orthopedic and cancer surgery.

Orthopedic surgery and surgery for cancer are major risk factors for venous thromboembolism (VTE). Deep vein thrombosis (DVT) can occur in up to 50% of patients after major orthopedic surgery. The rate of VTE after cancer surgery varies according to the type of surgery, with rates as high as those after orthopedic surgery in certain settings. Use of thromboprophylaxis in these high-risk settings is well established and recent studies inform the type and duration of thromboprophylaxis. With major orthopedic surgery, there has been a shift from use of low molecular weight heparins (LMWHs) to direct oral anticoagulants (DOACs) along with renewed interest in aspirin as a thromboprophylaxis agent. Recent studies have also informed optimal thromboprophylaxis strategies after nonmajor orthopedic surgery. Use of thromboprophylaxis after major cancer surgery for cancer is established and recent evidence has focused on the potential benefits of extended-duration thromboprophylaxis. This review will summarize emerging evidence for thromboprophylaxis after orthopedic and cancer surgery with a view to providing clinicians with concise and actionable guidance for best practice.

A physician survey of perioperative neuraxial anesthesia management in patients on a direct oral anticoagulant.

BACKGROUND: The perioperative management of patients taking a direct oral anticoagulant (DOAC) who require a high-bleed-risk surgery and/or neuraxial anesthesia is uncertain. We surveyed clinician practices relating to DOAC interruption and related perioperative management in patients having high-bleed-risk surgery with neuraxial anesthesia, and assess the suitability of a randomized trial of different perioperative DOAC management strategies. METHODS: We surveyed members of the American Society of Regional Anesthesia and Pain Medicine, the Canadian Anesthesia Society and Thrombosis Canada. We developed four clinical scenarios involving DOAC-treated patients who required anticoagulant interruption for elective high-bleed-risk surgery. In three scenarios, patients were to receive neuraxial anesthesia, and in one scenario they were to receive general anesthesia. We also asked about the merit of a randomized trial to compare a 2-day versus longer (3- to 5-day) duration of DOAC interruption. RESULTS: There were 399 survey respondents of whom 356 (89%) were anesthetists and 43 (11%) were medical specialists. The responses indicate uncertainty about the DOAC interruption interval for high-bleed-risk surgery and/or neuraxial anesthesia; anesthetists favor 3- to 5-day interruption whereas medical specialists favor 2-day interruption. Anesthetists were unwilling to proceed with neuraxial anesthesia in patients with a 2-day DOAC interruption interval, preferring to cancel the surgery or switch to general anesthesia. There is general agreement on the need for a randomized trial in this field to compare a 2-day and a 3- to 5-day DOAC interruption management strategy. CONCLUSIONS: There is variability in practices relating to the perioperative management of DOAC-treated patients who require a high-bleed-risk surgery with neuraxial anesthesia; this variability relates to the duration of DOAC interruption in such patients.

Effect of Direct Oral Anticoagulant, Patient, and Surgery Characteristics on Clinical Outcomes in the Perioperative Anticoagulation Use for Surgery Evaluation Study.

Introduction The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) Study assessed a standardized perioperative management strategy in patients with atrial fibrillation who were taking a direct oral anticoagulant (DOAC) and required an elective surgery or procedure. The aim of this substudy is to analyze the safety of this management strategy across different patient subgroups, according to four presurgical variables: (1) DOAC type and dose, (2) surgery/procedure bleed risk, (3) patient renal function, and (4) age. Methods Clinical outcomes analyzed included major bleeding (MB), arterial thromboembolism, any bleeding, and any thromboembolism. We used descriptive statistics to summarize clinical outcomes, where the frequency, proportion, and 95% confidence interval were reported. Fisher's exact tests were used for testing the null hypothesis of independence between the clinical outcome and patient characteristic, where the test p -values were reported. Results There were 3,007 patients with atrial fibrillation requiring perioperative DOAC management. There was no significant difference in bleeding or thromboembolic outcomes according to DOAC type/dose regimen, renal function, or patient age. The rate of MB was significantly higher with high bleed risk procedures than low bleed risk procedures in apixaban-treated patients (2.9 vs. 0.59%; p < 0.01), but not in dabigatran-treated patients (0.88 vs. 0.91%; p = 1.0) or rivaroxaban-treated patients (2.9 vs. 1.3%; p = 0.06). The risk for thromboembolism did not differ according to surgery/procedure-related bleed risk. Conclusion Our results suggest that in DOAC-treated patients who received standardized perioperative management, surgical bleed risk is an important determinant of bleeding but not thromboembolic outcomes, although this finding was not consistent across all DOACs. There were no differences in bleeding and thromboembolism according to DOAC type and dose, renal function, or age.

Predictors of preprocedural direct oral anticoagulant levels in patients having an elective surgery or procedure.

The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) study prospectively evaluated a prespecified periprocedural-interruption strategy of direct oral anticoagulants (DOACs) among patients with atrial fibrillation. Logistic regression analyses were performed to identify clinical parameters associated with residual DOAC levels ≥30 ng/mL or ≥50 ng/mL. Patients undergoing low-bleed-risk procedures were more likely to have residual levels of ≥30 ng/mL and ≥50 ng/mL. For low-risk procedures, age ≥75 years, female sex, a creatinine clearance (CrCl) <50 mL/min, and an interruption of <36 hours were associated with a greater likelihood of levels ≥30 ng/mL, whereas age ≥75 years, female sex, a CrCl of <50 mL/min, and standard DOAC dosing were associated with levels ≥50 ng/mL. For high-risk procedures, weight of <70 kg, CrCl <50 mL/min, and standard DOAC dosing were associated with residual levels ≥30 ng/mL, whereas female sex was associated with levels ≥50 ng/mL. For low-risk procedures, apixaban was associated with a higher likelihood of levels ≥30 ng/mL as compared with dabigatran (P = .0019) and of levels ≥50 ng/mL when compared with rivaroxaban (P = .0003). For high-risk procedures, apixaban was marginally associated with a higher likelihood of residual levels ≥30 ng/mL when compared with dabigatran (P = .05), whereas rivaroxaban was associated with a higher likelihood of levels ≥30 ng/mL as compared with apixaban. Further study is required to determine whether adjustments to perioperative plans based on these clinical parameters could result in a lower risk of residual DOAC levels. The PAUSE trial was registered at www.clinicaltrials.gov as #NCT2228798.

Management of hemostatic complications in acute leukemia: Guidance from the SSC of the ISTH.

Patients with acute leukemia frequently develop thrombocytopenia and hemostatic complications caused by coagulopathy. Coagulopathy complicates the management of these patients and can lead to significant morbidity and mortality. This guidance document aims to review and provide guidance on the management of hemostatic complications in adult patients with acute leukemia, addressing four main issues, including platelet transfusion, disseminated intravascular coagulation, L-asparaginase-related hypofibrinogenemia, and the use of antifibrinolytic agents.

Structure and function of a perioperative anticoagulation management clinic.

BACKGROUND: The perioperative management of patients who are receiving an anticoagulant and require a surgery/procedure is well-informed by multiple clinical studies, but an assessment of the delivery of such management is lacking. Describing the structure and function of a perioperative anticoagulation clinic provides a model for delivery of such patient care. METHODS: We examined the operational model of a perioperative anticoagulation clinic. We describe the processing and management of patients receiving anticoagulant therapy who require elective surgery or procedure, including anticoagulant interruption, resumption and consideration for bridging therapy. We also describe the patient profile assessed over an 18-month period, and the potential benefits of this clinic to patients for perioperative management and education. RESULTS: During an 18-month period, 1061 patients were assessed. Atrial fibrillation and venous thromboembolism were the most common indications for anticoagulant therapy, comprising 55.0% and 26.5% of patients, respectively; 44.1% of patients were taking warfarin, 37.1% were taking direct oral anticoagulants, and 12.3% were receiving low-molecular-weight heparin. The key components of this clinic model emphasizes a patient-centered approach to perioperative anticoagulant management based on evidence-based management protocols, alongside patient and family education that is delivered by a multi-disciplinary team approach. CONCLUSIONS: Our perioperative anticoagulation clinic model provides one approach to the delivery of perioperative anticoagulant management, with the potential to optimize patient safety, improve patient education, and minimize health care costs.