Periprocedural bridging anticoagulation in patients with venous thromboembolism: A registry- based cohort study

BackgroundUse of bridging anticoagulation increases a patient’s bleeding risk without clear evidence of thrombotic prevention among warfarin- treated patients with atrial fibrillation. Contemporary use of bridging anticoagulation among warfarin- treated patients with venous thromboembolism (VTE) has not been studied.MethodsWe identified warfarin- treated patients with VTE who temporarily stopped warfarin for a surgical procedure between 2010 and 2018 at six health systems. Using the 2012 American College of Chest Physicians guideline, we assessed use of periprocedural bridging anticoagulation based on recurrent VTE risk. Recurrent VTE risk and 30- day outcomes (bleeding, thromboembolism, emergency department visit) were each assessed using logistic regression adjusted for multiple procedures per patient.ResultsDuring the study period, 789 warfarin- treated patients with VTE underwent 1529 procedures (median, 2; interquartile range, 1- 4). Unadjusted use of bridging anticoagulation was more common in patients at high risk for VTE recurrence (99/171, 57.9%) than for patients at moderate (515/1078, 47.8%) or low risk of recurrence (134/280, 47.86%). Bridging anticoagulation use was higher in high- risk patients compared with low- or moderate- risk patients in both unadjusted (P = .013) and patient- level cluster- adjusted analyses (P = .031). Adherence to American College of Chest Physicians guidelines in high- and low- risk patients did not change during the study period (odds ratio, 0.98 per year; 95% confidence interval, 0.91- 1.05). Adverse events were rare and not statistically different between the two treatment groups.ConclusionsBridging anticoagulation was commonly overused among low- risk patients and underused among high- risk patients treated with warfarin for VTE. Adverse events were rare and not different between the two treatment groups.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156139/2/jth14903_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156139/1/jth14903.pd

Comparison of temporary interruption with continuation of direct oral anticoagulants for low bleeding risk procedures

INTRODUCTION: Limited data is available on the rates of bleeding and thromboembolic events for patients undergoing low bleeding risk procedures while taking direct oral anticoagulants (DOAC). METHODS: Adults taking DOAC in the Michigan Anticoagulation Quality Improvement Initiative (MAQI(2)) database who underwent a low bleeding risk procedure between May 2015 and Sep 2019 were included. Thirty-day bleeding (of any severity), thromboembolic events, and death were compared between DOAC temporarily interrupted and continued uninterrupted groups. Adverse event rates were compared using an inverse probability weighting propensity score. RESULTS: There were 820 patients who underwent 1412 low risk procedures. DOAC therapy was temporarily interrupted in 371 (45.2%) patients (601 [42.6%] procedures) and continued uninterrupted in 449 (54.8%) patients (811 [57.4%] procedures). DOAC patients with temporary interruptions were more likely to have diabetes, prior stroke or TIA, prior bleeding, higher CHA2DS2-VASc, and higher modified HAS-BLED scores. DOAC interruption was common for gastrointestinal endoscopy, electrophysiology device implantation, and cardiac catheterization while it was less common for cardioversion, dermatologic procedures, and subcutaneous injection. After propensity score adjustment, bleeding risk was lower in the DOAC temporary interruption group (OR 0.62, 95% CI 0.41-0.95) as compared to the group with continuous DOAC use. Rates of thromboembolic events and death did not differ significantly between the two groups. CONCLUSIONS: DOAC-treated patients undergoing low bleeding risk procedures may experience lower rates of bleeding when DOAC is temporarily interrupted. Prospective studies focused on low bleeding risk procedures are needed to identify the safety DOAC management strategy

Assessment of an Intervention to Reduce Aspirin Prescribing for Patients Receiving Warfarin for Anticoagulation

Importance: For some patients receiving warfarin, adding aspirin (acetylsalicylic acid) increases bleeding risk with unclear treatment benefit. Reducing excess aspirin use could be associated with improved clinical outcomes. Objective: To assess changes in aspirin use, bleeding, and thrombosis event rates among patients treated with warfarin. Design, Setting, and Participants: This pre-post observational quality improvement study was conducted from January 1, 2010, to December 31, 2019, at a 6-center quality improvement collaborative in Michigan among 6738 adults taking warfarin for atrial fibrillation and/or venous thromboembolism without an apparent indication for concomitant aspirin. Statistical analysis was conducted from November 26, 2020, to June 14, 2021. Intervention: Primary care professionals for patients taking aspirin were asked whether an ongoing combination aspirin and warfarin treatment was indicated. If not, then aspirin was discontinued with the approval of the managing clinician. Main Outcomes and Measures: Outcomes were assessed before and after intervention for the primary analysis and before and after 24 months before the intervention (when rates of aspirin use first began to decrease) for the secondary analysis. Outcomes included the rate of aspirin use, bleeding, and thrombotic outcomes. An interrupted time series analysis assessed cumulative monthly event rates over time. Results: A total of 6738 patients treated with warfarin (3160 men [46.9%]; mean [SD] age, 62.8 [16.2] years) were followed up for a median of 6.7 months (IQR, 3.2-19.3 months). Aspirin use decreased slightly from a baseline mean use of 29.4% (95% CI, 28.9%-29.9%) to 27.1% (95% CI, 26.1%-28.0%) during the 24 months before the intervention (P \u3c .001 for slope before and after 24 months before the intervention) with an accelerated decrease after the intervention (mean aspirin use, 15.7%; 95% CI, 14.8%-16.8%; P = .001 for slope before and after intervention). In the primary analysis, the intervention was associated with a significant decrease in major bleeding events per month (preintervention, 0.31%; 95% CI, 0.27%-0.34%; postintervention, 0.21%; 95% CI, 0.14%-0.28%; P = .03 for difference in slope before and after intervention). No change was observed in mean percentage of patients having a thrombotic event from before to after the intervention (0.21% vs 0.24%; P = .34 for difference in slope). In the secondary analysis, reducing aspirin use (starting 24 months before the intervention) was associated with decreases in mean percentage of patients having any bleeding event (2.3% vs 1.5%; P = .02 for change in slope before and after 24 months before the intervention), mean percentage of patients having a major bleeding event (0.31% vs 0.25%; P = .001 for change in slope before and after 24 months before the intervention), and mean percentage of patients with an emergency department visit for bleeding (0.99% vs 0.67%; P = .04 for change in slope before and after 24 months before the intervention), with no change in mean percentage of patients with a thrombotic event (0.20% vs 0.23%; P = .36 for change in slope before and after 24 months before the intervention). Conclusions and Relevance: This quality improvement intervention was associated with an acceleration of a preexisting decrease in aspirin use among patients taking warfarin for atrial fibrillation and/or venous thromboembolism without a clear indication for aspirin therapy. Reductions in aspirin use were associated with reduced bleeding. This study suggests that an anticoagulation clinic-based aspirin deimplementation intervention can improve guideline-concordant aspirin use

Outcomes of Direct Oral Anticoagulants with Aspirin Versus Warfarin with Aspirin for Atrial Fibrillation and/or Venous Thromboembolic Disease

Introduction: The direct oral anticoagulants (DOACs) including apixaban, dabigatran, edoxaban, and rivaroxaban are increasingly utilized for the management of venous thromboembolic disease (VTE) and/or non-valvular atrial fibrillation (NVAF). Adding aspirin (ASA) to warfarin or DOAC therapy increases bleeding risk. Patients on combination therapy with ASA and an anticoagulant were not well represented in clinical trials comparing DOACs to warfarin. We sought to compare bleeding and thrombotic outcomes with DOACs and ASA compared to warfarin and ASA in a non-trial setting. Methods: We conducted a retrospective registry-based cohort study of adults on DOAC or warfarin therapy for VTE and/or NVAF. Warfarin treated patients were followed by six anticoagulation clinics. Four out of the six clinics contributed data on their patients that were on DOACs in the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2) from January 2009 to June 2021. Patients were excluded if they had a history of heart valve replacement, recent myocardial infarction, or less than 3 months of follow-up. Two propensity matched cohorts (warfarin+ASA vs DOAC+ASA) of patients were analyzed based on ASA use at the time of study enrollment. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of arterial or venous thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room visits, hospitalizations, transfusions, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression. Results: We identified a total of 1,139 patients on DOACs plus ASA and 4,422 patients on warfarin plus ASA. After propensity matching, we compared two groups of 1,114 matched patients. DOAC treated patients were predominately on apixaban (62.3%) and rivaroxaban (30.4%), most often at therapeutic doses (Table 1). Patients were largely (90.5%) on low dose ASA (≤ 100 mg). Patient demographics, co-morbidities, indication for anticoagulation, history of bleeding or clotting, medications, and duration of follow-up were well-balanced after matching. Patients were followed for a median of 11.7 months (interquartile range 4.4 and 34 months). Patients treated with DOAC+ASA had 2.4 thrombotic events per 100 patient years compared to 2.2 thrombotic events per 100 patient years with warfarin+ASA (P=0.78). There were no significant differences observed between groups by thrombotic subtype (stroke, transient ischemic attack, pulmonary embolism, deep vein thrombosis, table 1). Bleeding was also similar with 30.1 bleeding events per 100 patient years with DOAC+ASA compared to 27.8 bleeds per 100 patient years with warfarin+ASA (P=0.24). There were no significant differences by bleeding subtype (table 1). Hospitalizations for clotting occurred less frequently with DOAC+ASA (0.9 hospitalizations per 100 patient years) compared to warfarin+ASA (1.7 hospitalizations per 100 patient years, P=0.03). Mortality, transfusions, and healthcare utilization were otherwise similar between the two groups. Conclusions: For patients on a DOAC versus warfarin with ASA for atrial fibrillation and/or venous thromboembolic disease without a recent myocardial infarction or heart valve replacement, bleeding and thrombotic outcomes were similar

Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication

Importance: It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes. Objective: To evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE). Design, Setting, and Participants: This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up. Exposures: Use of ASA concomitant with DOAC therapy. Main Outcomes and Measures: Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death. Results: Of the study cohort of 3280 patients (1673 [51.0%] men; mean [SD] age 68.2 [13.3] years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02). Conclusion and Relevance: Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit

Barriers and facilitators to reducing frequent laboratory testing for patients who are stable on warfarin: a mixed methods study of de-implementation in five anticoagulation clinics

Abstract Background Patients on chronic warfarin therapy require regular laboratory monitoring to safely manage warfarin. Recent studies have challenged the need for routine monthly blood draws in the most stable warfarin-treated patients, suggesting the safety of less frequent laboratory testing (up to every 12 weeks). De-implementation efforts aim to reduce the use of low-value clinical practices. To explore barriers and facilitators of a de-implementation effort to reduce the use of frequent laboratory tests for patients with stable warfarin management in nurse/pharmacist-run anticoagulation clinics, we performed a mixed-methods study conducted within a state-wide collaborative quality improvement collaborative. Methods Using a mixed-methods approach, we conducted post-implementation semi-structured interviews with a total of eight anticoagulation nurse or pharmacist staff members at five participating clinic sites to assess barriers and facilitators to de-implementing frequent international normalized ratio (INR) laboratory testing among patients with stable warfarin control. Interview guides were based on the Tailored Implementation for Chronic Disease (TICD) framework. Informed by interview themes, a survey was developed and administered to all anticoagulation clinical staff (n = 62) about their self-reported utilization of less frequent INR testing and specific barriers to de-implementing the standard (more frequent) INR testing practice. Results From the interviews, four themes emerged congruent with TICD domains: (1) staff overestimating their actual use of less frequent INR testing (individual health professional factors), (2) barriers to appropriate patient engagement (incentives and resources), (3) broad support for an electronic medical record flag to identify potentially eligible patients (incentives and resources), and (4) the importance of personalized nurse/pharmacist feedback (individual health professional factors). In the survey (65% response rate), staff report offering less frequent INR testing to 56% (46–66%) of eligible patients. Most survey responders (n = 24; 60%) agreed that an eligibility flag in the electronic medical record would be very helpful. Twenty-four (60%) respondents agreed that periodic, personalized feedback on use of less frequent INR testing would also be helpful. Conclusions Leveraging information system notifications, reducing additional work load burden for participating patients and providers, and providing personalized feedback are strategies that may improve adoption and utilization new policies in anticoagulation clinics that focus on de-implementation.https://deepblue.lib.umich.edu/bitstream/2027.42/137702/1/13012_2017_Article_620.pd

Selenoprotein gene nomenclature

The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates

Experimental strategies for microRNA target identification

MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression in most biological processes. They act by guiding the RNAi-induced silencing complex (RISC) to partially complementary sequences in target mRNAs to suppress gene expression by a combination of translation inhibition and mRNA decay. The commonly accepted mechanism of miRNA targeting in animals involves an interaction between the 5′-end of the miRNA called the ‘seed region’ and the 3′ untranslated region (3′-UTR) of the mRNA. Many target prediction algorithms are based around such a model, though increasing evidence demonstrates that targeting can also be mediated through sites other than the 3′-UTR and that seed region base pairing is not always required. The power and validity of such in silico data can be therefore hindered by the simplified rules used to represent targeting interactions. Experimentation is essential to identify genuine miRNA targets, however many experimental modalities exist and their limitations need to be understood. This review summarizes and critiques the existing experimental techniques for miRNA target identification