Adverse events in low versus normal body weight patients prescribed apixaban for atrial fibrillation.

Safety and efficacy of direct oral anticoagulants (DOAC) in low weight patients with atrial fibrillation (AF) is unclear due to few low body weight patients enrolled in clinical trials. To assess bleeding and thrombotic event rates for patients with AF that are prescribed apixaban and have a low versus normal body weight. We analyzed patients with AF prescribed apixaban from 2017 to 2020 with at least 12 months of follow-up. Patients were divided into low [< 60 kg (kg)] and normal (60-100 kg) weight cohorts. Bleeding and thrombotic event rates were compared. Poisson regression and Cox proportional hazard models were used to estimate adjusted adverse event rates. A total of 545 patients met inclusion criteria. In the unadjusted analysis, there was an increase in non-major bleeding events requiring an Emergency Department visit more often in the low versus normal weight cohort (10.8 versus 7.4 per 100 patient-years, p = 0.15). Thrombotic event rates also occurred more often in the lower versus normal weight cohort (2.4 versus 0.9 per 100 patient-years, p = 0.09). However, adjusted analysis found no statistically significant difference in bleeding or thrombotic events between low and normal weight cohorts. The adjusted hazard ratio for bleeding was similar between the two weight cohorts. The use of apixaban in low body weight patients was not associated with higher rates of bleeding or thrombotic events, compared to those with normal body weight, after adjusting for potential confounding covariates. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in these patients.

COVID-19 risk index (CRI): a simple and validated emergency department risk score that predicts mortality and the need for mechanical ventilation.

Although certain risk factors have been associated with morbidity and mortality, validated emergency department (ED) derived risk prediction models specific to coronavirus disease 2019 (COVID-19) are lacking. The objective of this study is to describe and externally validate the COVID-19 risk index (CRI). A large retrospective longitudinal cohort study was performed to analyze consecutively hospitalized patients with COVID-19. Multivariate regression using clinical data elements from the ED was used to create the CRI. The results were validated with an external cohort of 1799 patients from the MI-COVID19 database. The primary outcome was the composite of the need for mechanical ventilation or inpatient mortality, and the secondary outcome was inpatient mortality. A total of 1020 patients were included in the derivation cohort. A total of 236 (23%) patients in the derivation cohort required mechanical ventilation or died. Variables independently associated with the primary outcome were age ≥ 65 years, chronic obstructive pulmonary disease, chronic kidney disease, cerebrovascular disease, initial D-dimer > 1.1 µg/mL, platelet count < 150 K/µL, and severity of SpO2:FiO2 ratio. The derivation cohort had an area under the receiver operator characteristic curve (AUC) of 0.83, and 0.74 in the external validation cohort Calibration shows close adherence between the observed and expected primary outcomes within the validation cohort. The CRI is a novel disease-specific tool that assesses the risk for mechanical ventilation or death in hospitalized patients with COVID-19. Discrimination of the score may change given continuous updates in contemporary COVID-19 management and outcomes.

Thromboembolic prevention and anticoagulant therapy during the COVID-19 pandemic: updated clinical guidance from the anticoagulation forum.

Thromboembolism is a common and deadly consequence of COVID-19 infection for hospitalized patients. Based on clinical evidence pre-dating the COVID-19 pandemic and early observational reports, expert consensus and guidance documents have strongly encouraged the use of prophylactic anticoagulation for patients hospitalized for COVID-19 infection. More recently, multiple clinical trials and larger observational studies have provided evidence for tailoring the approach to thromboprophylaxis for patients with COVID-19. This document provides updated guidance for the use of anticoagulant therapies in patients with COVID-19 from the Anticoagulation Forum, the leading North American organization of anticoagulation providers. We discuss ambulatory, in-hospital, and post-hospital thromboprophylaxis strategies as well as provide guidance for patients with thrombotic conditions who are considering COVID-19 vaccination.

Antiphospholipid antibodies and recurrent thrombosis after a first unprovoked venous thromboembolism.

It is uncertain whether antiphospholipid antibodies (APAs) increase the risk of recurrence after a first unprovoked venous thromboembolism (VTE). We tested for anticardiolipin antibodies, anti-ß2 glycoprotein 1 antibodies, and lupus anticoagulant on 2 occasions ∼6 months apart in 307 patients with a first unprovoked VTE who were part of a prospective cohort study. We then determined if APAs were associated with recurrent thrombosis in the 290 patients who stopped anticoagulant therapy in response to negative D-dimer results. Compared with those without an APA, the hazard ratios for recurrent VTE were 1.8 (95% confidence interval [CI], 0.9-3.7; P = .09) in the 25.9% of patients with an APA on ≥1 occasions, 2.7 (95% CI, 1.1-.7; P = .03) in the 9.0% of patients with the same APA on 2 occasions, and 4.5 (95% CI, 1.5-13.0; P = .006) in the 3.8% of patients with 2 or 3 different APA types on either the same or different occasions. There was no association between having an APA and D-dimer levels. We conclude that having the same type of APA on 2 occasions or having >1 type of APA on the same or different occasions is associated with recurrent thrombosis in patients with a first unprovoked VTE who stop anticoagulant therapy in response to negative D-dimer tests. APA and D-dimer levels seem to be independent predictors of recurrence in patients with an unprovoked VTE. This trial was registered at www.clinicaltrials.gov as #NCT00720915.

Use of apixaban and rivaroxaban in young adults with acute venous thromboembolism: a multi-center retrospective case series.

Since 2012 four direct oral anticoagulants (DOAC) have been approved by the US Food and Drug Administration (FDA) for treatment of acute venous thromboembolism (VTE). Clinical trials comparing DOACs to warfarin included more than 13,500 patients. However, included patients were all age 39 years or older. We sought to describe real-world use of DOACs among young adults with acute VTE. Multi-center retrospective case series of young adult patients (age 18-40 years) at two large academic medical centers who initiated any DOAC for VTE therapy in 2015 or 2016. Thrombotic and bleeding events as well as off-label drug use were described using summary statistics. Fifty-seven patients were identified (63.2% female). One of the 57 patients (1.8%) had a thromboembolic event. Seven of the 57 patients (12.3%) experienced a bleeding event, one categorized as a major bleed and six being categorized as clinically relevant non-major bleeding. One of the ten (10%) patients receiving apixaban was not initiated on the FDA-recommended 10 mg twice daily for the first 7 days. Seven of the 47 (14.9%) patients receiving rivaroxaban were not initiated on the FDA-recommended 15 mg twice daily dosing for the first 21 days. Bleeding occurred in approximately 14% of young adult patients treated with DOAC therapy. However, only one patient had their DOAC discontinued due to a major bleeding event. Recurrence of DVT while on DOAC therapy was rare.

Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum.

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes. While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic. It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients. Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients. Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience. The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19. We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.

Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia: A Multihospital Cohort Study.

Background: Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration. Objective: To examine predictors and outcomes associated with excess duration of antibiotic treatment. Design: Retrospective cohort study. Setting: 43 hospitals in the Michigan Hospital Medicine Safety Consortium. Patients: 6481 general care medical patients with pneumonia. Measurements: The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care-associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability of treatment. Results: Two thirds (67.8% [4391 of 6481]) of patients received excess antibiotic therapy. Antibiotics prescribed at discharge accounted for 93.2% of excess duration. Patients who had respiratory cultures or nonculture diagnostic testing, had a longer stay, received a high-risk antibiotic in the prior 90 days, had community-acquired pneumonia, or did not have a total antibiotic treatment duration documented at discharge were more likely to receive excess treatment. Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge. Limitation: Retrospective design; not all patients could be contacted to report 30-day outcomes. Conclusion: Patients hospitalized with pneumonia often receive excess antibiotic therapy. Excess antibiotic treatment was associated with patient-reported adverse events. Future interventions should focus on whether reducing excess treatment and improving documentation at discharge improves outcomes. Primary Funding Source: Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program.

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum.

Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non-specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.

Creatinine monitoring patterns in the setting of direct oral anticoagulant therapy for non-valvular atrial fibrillation.

Guidelines and experts note that patients with atrial fibrillation require regular renal function monitoring to ensure safe use of direct oral anticoagulants (DOACs). Insufficient monitoring could lead to inappropriate dosing and adverse events. Our objective was to describe the frequency of insufficient creatinine monitoring among patients on DOACs, and to describe clinical factors associated with insufficient monitoring. We hypothesized that renal impairment would be associated with insufficient monitoring. A retrospective cohort study was performed with data from the Michigan Anticoagulant Quality Improvement Initiative. Patients were included if they initiated DOAC therapy for stroke prevention related to atrial fibrillation, remained on therapy for ≥ 1 year, and had baseline creatinine and weight measurements. Creatinine clearance (CrCl) was calculated via Cockcroft-Gault equation. Our outcome was the presence of insufficient creatinine monitoring, defined as: < 1 creatinine level/year for patients with CrCl > 50, or < 2 creatinine levels/year for patients with CrCl ≤ 50. Multivariable analysis was done via logistic regression. Study population included 511 patients. In overall, 14.0% of patients received insufficient monitoring. Among patients with CrCl > 50, 11.5% had < 1 creatinine level/year. Among patients with CrCl ≤ 50, 27.1% received < 2 creatinine levels/year. Baseline renal dysfunction was associated with a higher likelihood of insufficient creatinine monitoring (adjusted odds ratio 3.64, 95% confidence interval 1.81-7.29). This shows a significant gap in the monitoring of patients on DOACs-patients with renal impairment are already at higher risk for adverse events. Future studies are needed to describe the barriers in monitoring these patients and to identify how to optimally address them.

Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation.

BACKGROUND: It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS: We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. RESULTS: In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). CONCLUSIONS: In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.).

Mind the gap: results of a multispecialty survey on coordination of care for peri-procedural anticoagulation.

To understand how physicians from various specialties perceive coordination of care when managing peri-procedural anticoagulation. Cross-sectional survey of cardiologists, gastroenterologists, and primary care physicians (PCPs) in an integrated health system (N = 251). The survey began with a vignette of a patient with atrial fibrillation co-managed by his PCP, cardiologist, and an anticoagulation clinic who must hold warfarin for a colonoscopy. Respondents' experiences and opinions around responsibilities and institutional support for managing peri-procedural anticoagulation were elicited using multiple choice questions. We examined differences in responses across specialties using Chi square analysis. The response rate was 51% (n = 127). 52% were PCPs, 28% cardiologists, and 21% gastroenterologists. Nearly half (47.2%) of respondents believed that the cardiologist should be primarily responsible for managing peri-procedural anticoagulation, while fewer identified the PCP (25.2%), anticoagulation clinic (21.3%), or gastroenterologist (6.3%; p = 0.09). Respondents across specialties had significantly different approaches to deciding how to manage the clinical case presented (p < 0.001). Most cardiologists (60.0%) would decide whether to offer bridging without consulting with other providers or clinical resources, while most PCPs would decide after consulting clinical resources (57.6%). Gastroenterologists would most often (46.2%) defer the decision to another provider. A majority of all three specialties agreed that their institution could do more to help manage peri-procedural anticoagulation, and there was broad support (88.1%) for anticoagulation clinics' managing all aspects of peri-procedural anticoagulation. Providers across specialties agree that their institution could do more to help manage peri-procedural anticoagulation, and overwhelmingly support anticoagulation clinics' taking responsibility.

Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials.

Randomized controlled trials (RCTs) examining warfarin use for stroke prevention in atrial fibrillation (AF) may not accurately reflect real-world populations. We aimed to determine the representativeness of the RCT populations to real-world patients and to describe differences in the characteristics of trial populations from trial eligible patients in a real-world setting. We hypothesized that a significant fraction of real-world patients would not qualify for the RE-LY, ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the studies may have more strokes and bleeding events. We compared the inclusion and exclusion criteria, patient characteristics, and clinical outcomes from RE-LY, ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI2), a regional network of six community- and academic-based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI2 registry taking warfarin, approximately 40-60% would meet the selection criteria used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%). The most common reasons for exclusion from one or more trial were anemia (15.1%), other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial-eligible MAQI2 patients were older, more frequently female, with a higher rate of paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and previous myocardial infarction than the trial populations. MAQI2 patients eligible for each trial had a lower rate of stroke and similar rate of major bleeding than was observed in the trials. A sizable proportion of real-world AF patients managed in anticoagulation clinics would not have been eligible for the RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and bleeding risk among real-world AF patients on warfarin may not be congruent with published clinical trial data.

Patterns and Predictors of Peripherally Inserted Central Catheter Occlusion: The 3P-O Study.

PURPOSE: To evaluate patterns and predictors of peripherally inserted central catheter (PICC)-related occlusion. MATERIALS AND METHODS: Data from a multihospital study were used to examine factors associated with PICC occlusion. Occlusion was defined if documented in the medical record or when tissue plasminogen activator was administered for occlusion-related concerns. Mixed-effects logistic regression was used to predict occlusion, controlling for patient-, provider-, device-, and hospital-level characteristics. RESULTS: A total of 14,278 PICCs placed in 13,408 patients were included. Of these, occlusion developed in 1,716 PICCs (12%) in 1,684 patients. The most common indications for PICC insertion were intravenous antibiotic therapy (32.7%), difficult intravenous access (21.5%), and central access (13.7%). PICCs placed in the right arm had decreased odds of occlusion compared with those in the left arm (odds ratio [OR] = 0.82; 95% confidence interval [CI] = 0.72-0.94). Verification of catheter tip position following insertion was associated with reduction in occlusion (OR = 0.75; 95% CI = 0.61-0.92). Although normal saline solution or heparin flushes did not reduce occlusion, PICCs flushed with normal saline solution and "locked" with heparin were less likely to become occluded (OR = 0.54; 95% CI = 0.33-0.88). Compared with single-lumen devices, double- and triple-lumen PICCs were associated with greater incidences of occlusion (double, OR = 3.07; 95% CI = 2.56-3.67; triple, OR = 3.72; 95% CI = 2.92-4.74). Catheter tip malposition was also associated with occlusion (OR = 1.46; 95% CI = 1.14-1.87). CONCLUSIONS: Several patient, provider, and device characteristics appear associated with PICC occlusion. Interventions targeting these factors may prove valuable in reducing this complication.

SAMe-TT2R2 predicts quality of anticoagulation in patients with acute venous thromboembolism: The MAQI2 experience.

A high SAMe-TT2R2 score predicted poor warfarin control and adverse events among atrial fibrillation patients. However, the SAMe-TT2R2 score has not been well validated in venous thromboembolism (VTE) patients. A cohort of 1943 warfarin-treated patients with acute VTE was analyzed to correlate the SAMe-TT2R2 score with time in therapeutic range (TTR) and clinical adverse events. A TTR <60% was more frequent among patients with a high (>2) versus low (0-1) SAMe-TT2R2 score (63.4% vs 52.3%, p<0.0001). A high SAMe-TT2R2 score (>2) correlated with increased overall adverse events (7.9 vs 4.5 overall adverse events/100 patient years, p=0.002), driven primarily by increased recurrent VTE rates (4.2 vs 1.5 recurrent VTE/100 patient years, p=0.0003). The SAMe-TT2R2 score had a modest predictive ability for international normalized ratio (INR) quality and adverse clinical events among warfarin-treated VTE patients. The utility of the SAMe-TT2R2 score to guide clinical decision-making remains to be investigated.

Prescribing trends of atrial fibrillation patients who switched from warfarin to a direct oral anticoagulant.

Direct oral anticoagulant (DOAC) agents offer several lifestyle and therapeutic advantages for patients relative to warfarin in the treatment of atrial fibrillation (AF). These alternative agents are increasingly used in the treatment of AF, however the adoption practices, patient profiles, and reasons for switching to a DOAC from warfarin have not been well studied. Through the Michigan Anticoagulation Quality Improvement Initiative, abstracted data from 3873 AF patients, enrolled between 2010 and 2015, were collected on demographics and comorbid conditions, stroke and bleeding risk scores, and reasons for anticoagulant switching. Over the study period, patients who switched from warfarin to a DOAC had similar baseline characteristics, risk scores, and insurance status but differed in baseline CrCl. The most common reasons for switching were patient related ease of use concerns (37.5%) as opposed to clinical reasons (16.5% of patients). Only 13% of patients that switched to a DOAC switched back to warfarin by the end of the study period.

Management of Elective Surgery and Emergent Bleeding with Direct Oral Anticoagulants.

PURPOSE OF REVIEW: The purpose of this review was to offer practical management strategies for when patients receiving direct oral anticoagulants require elective surgery or present with bleeding complications. RECENT FINDINGS: Clinical practice guidelines are now available on the timing of periprocedural interruption of treatment with the newer direct oral anticoagulants based on their pharmacodynamics and pharmacokinetics and based on findings from cohort studies and clinical trials. An antibody that reverses the effects of dabigatran is now available, and a factor Xa decoy is being developed as an antidote to apixaban, betrixaban, edoxaban, and rivaroxaban. The timing of interruption of direct oral anticoagulants for elective surgery is based on multiple factors, including pharmacologic properties and interactions, the patient's renal function, and the type of planned surgery. There is little role for low-molecular-weight heparin bridging. Idarucizumab is the treatment of choice for dabigatran-related life-threatening bleeding, while andexanet alfa is being developed to reverse factor Xa inhibitors.

Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. The treatment of VTE is undergoing tremendous changes with the introduction of the new direct oral anticoagulants and clinicians need to understand new treatment paradigms. This article, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. Well-managed warfarin therapy remains an important anticoagulant option and it is hoped that anticoagulation providers will find the guidance contained in this article increases their ability to achieve optimal outcomes for their patients with VTE Pivotal practical questions pertaining to this topic were developed by consensus of the authors and were derived from evidence-based consensus statements whenever possible. The medical literature was reviewed and summarized using guidance statements that reflect the consensus opinion(s) of all authors and the endorsement of the Anticoagulation Forum's Board of Directors. In an effort to provide practical and implementable information about VTE and its treatment, guidance statements pertaining to choosing good candidates for warfarin therapy, warfarin initiation, optimizing warfarin control, invasive procedure management, excessive anticoagulation, subtherapeutic anticoagulation, drug interactions, switching between anticoagulants, and care transitions are provided.

Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance <50 mL/min and 23 (12.2 %) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

Preclinical and clinical data for factor Xa and "universal" reversal agents.

Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoy molecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development. This review summarizes the published data to date on both drugs, which have the potential to change the management approach to patients with FXa inhibitoreassociated major hemorrhage.