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A lack in patient knowledge of warfarin therapy is associated with poor adherence. This knowledge gap may result in a lower INR Time in Therapeutic Range (TTR). To investigate association between patient anticoagulation knowledge and warfarin control. Michigan Anticoagulation Quality Improvement Initiative (MAQI

ImportanceFor 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.ObjectiveTo assess changes in aspirin use, bleeding, and thrombosis event rates among patients treated with warfarin.Design, Setting, and ParticipantsThis 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.InterventionPrimary 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 MeasuresOutcomes 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.ResultsA 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 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 RelevanceThis 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.

Background Use 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. Methods We 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. Results During 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. Conclusions Bridging 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.

Introduction: Fibromuscular dysplasia (FMD) is a non-inflammatory vasculopathy associated with arterial stenosis, aneurysm, dissection, and tortuosity. We investigated racial differences in clinical manifestations and events of multifocal FMD. Methods: Demographics, medical history, presenting signs and symptoms, and major vascular events were queried from the US Registry for FMD and stratified into White or Black based on self-identified race. Results: Of the 1897 female patients (pts) with multifocal FMD and race reported from 14 sites as of 12/23/2020, there were 1697 (89.5 %) White, 123 (6.5 %) Black, 52 (2.7%) Hispanic, and 25 (1.3%) pts of other races. Given a small number of pts in other groups, analysis was only performed between White and Black pts. Age at diagnosis and at first sign/symptom was similar between the two groups. Black pts were more likely to have a history of hypertension (p=0.009), stroke (p=0.002), and subarachnoid hemorrhage (p Conclusion: We noted a low number of Black patients enrolled in the US Registry for FMD at FMD specialty centers. There were differences in clinical manifestations, events, and pattern of vascular involvement among Black and White patients enrolled in US Registry, the mechanisms for which require additional study.

Patients’ international normalized ratios (INRs) often fall slightly out of range. In these cases, the American College of Chest Physicians (ACCP) guidelines suggest maintaining the current warfarin dose and retesting the INR within the following 2 weeks (watchful waiting). We sought to determine whether watchful waiting or dose changes for slightly out-of-range INRs is more effective in obtaining in-range INRs at follow-up. INRs and management strategies of warfarin-treated patients within the Michigan Anticoagulation Quality Improvement Initiative registry were analyzed. Management strategies included watchful waiting or dose changes. INRs slightly out of range (target range 2.0-3.0) and their associated management were identified. Multilevel mixed-effects logistic regression was used to estimate the probability of the next INR being in range, adjusted for clustering due to multiple out-of-range INRs per patient. A total of 45 351 slightly out-of-range INRs (ranging 1.50-1.99 and 3.01-3.49) from 8288 patients were identified. The next INR was slightly less likely to be in range with watchful waiting than with a dose change (predicted probabilities 58.9% vs 60.0%, P = 0.024). Although a significant statistical difference was detected in the probabilities of the next INR being back in range when managed by a dose change compared with watchful waiting following a slightly out-of-range INR, the magnitude of the difference was small and unlikely to represent clinical importance. Our study supports the current guideline recommendations for watchful waiting in cases of slightly out-of-range INRs values.

Background Fibromuscular dysplasia (FMD) is a nonatherosclerotic arterial disease that has a variable presentation including pulsatile tinnitus (PT). The frequency and characteristics of PT in FMD are not well understood. The objective of this study was to evaluate the frequency of PT in FMD and compare characteristics between patients with and without PT. Methods and Results Data were queried from the US Registry for FMD from 2009 to 2020. The primary outcomes were frequency of PT among the FMD population and prevalence of baseline characteristics, signs/symptoms, and vascular bed involvement in patients with and without PT. Of 2613 patients with FMD who were included in the analysis, 972 (37.2%) reported PT. Univariable analysis and multivariable logistic regression were performed to explore factors associated with PT. Compared with those without PT, patients with PT were more likely to have involvement of the extracranial carotid artery (90.0% versus 78.6%; odds ratio, 1.49; P =0.005) and to have higher prevalence of other neurovascular signs/symptoms including headache (82.5% versus 62.7%; odds ratio, 1.82; P P P Conclusions PT is common among patients with FMD. Patients with FMD who present with PT have higher rates of neurovascular signs/symptoms, cervical bruit, and involvement of the extracranial carotid arteries. The coexistence of the 2 conditions should be recognized, and providers who evaluate patients with PT should be aware of FMD as a potential cause.

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.

Cronobacter sakazakii (C. sakazakii) in viable but nonculturable (VBNC) state might evade traditional culture detection, and pose a serious threat to food safety. The objective of this study was to establish an improved propidium monoazide (PMAxx), combined with a single intact cell droplet digital PCR (SIC ddPCR) method for rapid and absolute quantification of VBNC C. sakazakii and apply it to the detection of several infant foods. In this study, we optimized the detection conditions for C. sakazakii, and determined the optimal PMAxx final concentration (8 μM), light exposure times (10 min), annealing temperature (58 °C) and elongation time (1 min). In addition, PMAxx-SIC ddPCR demonstrated a higher detection sensitivity and accuracy relative to real-time PCR (qPCR), with 23 CFU/mL in pure culture. Furthermore, PMAxx-SIC ddPCR was used to detect VBNC C. sakazakii in the actual infant food samples. A total of 240 samples were analyzed, out of which 6 samples turned out to be positive by the traditional culture method, whereas 11 samples were found as positive by PMAxx-SIC ddPCR. These results demonstrate that the presence of VBNC may cause the conventional culture-based method to underestimate the size of microbial population.

IMPORTANCE: It is not clear how often patients receive aspirin (acetylsalicylic acid) while receiving oral anticoagulation with warfarin sodium without a clear therapeutic indication for aspirin, such as a mechanical heart valve replacement, recent percutaneous coronary intervention, or acute coronary syndrome. The clinical outcomes of such patients treated with warfarin and aspirin therapy compared with warfarin monotherapy are not well defined to date. OBJECTIVE: To evaluate the frequency and outcomes of adding aspirin to warfarin for patients without a clear therapeutic indication for combination therapy. DESIGN, SETTING, AND PARTICIPANTS: A registry-based cohort study of adults enrolled at 6 anticoagulation clinics in Michigan (January 1, 2010, to December 31, 2017) who were receiving warfarin therapy for atrial fibrillation or venous thromboembolism without documentation of a recent myocardial infarction or history of valve replacement. EXPOSURE: Aspirin use without therapeutic indication. MAIN OUTCOMES AND MEASURES: Rates of any bleeding, major bleeding events, emergency department visits, hospitalizations, and thrombotic events at 1, 2, and 3 years. RESULTS: Of the study cohort of 6539 patients (3326 men [50.9%]; mean [SD] age, 66.1 [15.5] years), 2453 patients (37.5%) without a clear therapeutic indication for aspirin were receiving combination warfarin and aspirin therapy. Data from 2 propensity score–matched cohorts of 1844 patients were analyzed (warfarin and aspirin vs warfarin only). At 1 year, patients receiving combination warfarin and aspirin compared with those receiving warfarin only had higher rates of overall bleeding (cumulative incidence, 26.0%; 95% CI, 23.8%-28.3% vs 20.3%; 95% CI, 18.3%-22.3%; P

Supplemental material, 10.1177_1358863X18815971_Supplemental_Material for Missed opportunities to prevent upper GI hemorrhage: The experience of the Michigan Anticoagulation Quality Improvement Initiative by Jacob E Kurlander, Xiaokui Gu, James M Scheiman, Brian Haymart, Eva Kline-Rogers, Sameer D Saini, Scott Kaatz, James B Froehlich, Caroline R Richardson and Geoffrey D Barnes in Vascular Medicine

Background Fibromuscular dysplasia (FMD) is a noninflammatory arterial disease that predominantly affects women. The arterial manifestations may include beading, stenosis, aneurysm, dissection, or tortuosity. Objectives This study compared the frequency, location, and outcomes of FMD patients with aneurysm and/or dissection to those of patients without. Methods The U.S. Registry for FMD involves 12 clinical centers. This analysis included clinical history, diagnostic, and therapeutic procedure results for 921 FMD patients enrolled in the registry as of October 17, 2014. Results Aneurysm occurred in 200 patients (21.7%) and dissection in 237 patients (25.7%); in total, 384 patients (41.7%) had an aneurysm and/or a dissection by the time of FMD diagnosis. The extracranial carotid, renal, and intracranial arteries were the most common sites of aneurysm; dissection most often occurred in the extracranial carotid, vertebral, renal, and coronary arteries. FMD patients with dissection were younger at presentation (48.4 vs. 53.5 years of age, respectively; p Conclusions Patients with FMD have a high prevalence of aneurysm and/or dissection prior to or at the time of FMD diagnosis. Patients with dissection were more likely to experience ischemic events, and a significant number of patients with dissection or aneurysm underwent therapeutic procedures for these vascular events. Because of the high prevalence and associated morbidity in patients with FMD who have an aneurysm and/or dissection, it is recommended that every patient with FMD undergo one-time cross-sectional imaging from head to pelvis with computed tomographic angiography or magnetic resonance angiography.

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

Vibrio parahaemolyticus, a marine food-borne pathogen, has been proved to be a significant cause of human gastrointestinal disorders worldwide. In this study, a method of multiplex droplet digital PCR (ddPCR) based on primer and probe sequences of the tlh, tdh and ureR genes were developed and evaluated for the reliable quantification of V. parahaemolyticus cells in seafoods. The specificities of all primers and probes used in this study were validated on three standard strains of V. parahaemolyticus, 10 strains of Vibrio spp., and 22 strains of other bacteria by ddPCR and quantitative PCR (qPCR). Then the ddPCR system, primers, probe concentration and amplification procedures were optimized, and the templates with cell and genomic DNA (gDNA) were compared. The results showed that using cell as template could benefit for multiplex ddPCR, which performed higher linkage among three genes. This method improved sensitivity, specificity, accuracy, convenience, and reproducibility for the detection of V. parahaemolyticus, and the limit of detection (LOD) was 15 CFU/mL. In addition, the applicability of this method was compared with plate count and qPCR, and then verified to detect artificially contaminated seafood samples containing different concentrations of V. parahaemolyticus. The results indicated that the established method is stable, accurate, sensitive, range-wide, and has the potential to detect the three different genes of V. parahaemolyticus in food samples.

Immunomagnetic separation (IMS) is an effective method for specific enrichment and purification of target food-borne pathogens from complex food samples. To detect viable but non-culturable (VBNC) Vibrio parahaemolyticus (V. parahaemolyticus) with greater accuracy and sensitivity, we used an improved propidium monoazide (PMAxx) dye to eliminate dead cell interference in an IMS-PMAxx-real-time (quantitative) polymerase chain reaction (IMS-PMAxx-qPCR) assay. We prepared immunomagnetic beads (IMBs) using streptavidin-conjugated magnetic nanoparticles and biotinylated polyclonal antibodies, and optimized the reaction conditions to establish an IMS method for VBNC V. parahaemolyticus. We determined the optimal antibody amount (30 μg), IMBs volume (150 μL), incubation time (45 min), immunomagnetic separation time (4 min), and separation temperature (25 °C). The IMS-PMAxx-qPCR method could detect VBNC V. parahaemolyticus in raw shrimp samples at levels as low as 1.85 CFU/g without any pre-enrichment. The IMS-PMAxx-qPCR assay is highly sensitive, selective, simple, and rapid (

Use of bridging anticoagulation has been shown to be harmful and without benefit in warfarin-treated patients with atrial fibrillation. We performed a quasi-experimental interrupted time series analysis between 2010 and 2017 in the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) collaborative before and after the BRIDGE trial publication (July 2015). Predicted use of bridging at the end of the study period was calculated with and without the effect of the BRIDGE trial after adjustment for patient-level clustering. Predictors of bridging anticoagulation use in the post-BRIDGE trial period were analyzed. In adjusted analyses, the use of bridging anticoagulation declined from a predicted 27.8% (95% confidence interval, 20.5%-35.1%) to 13.6% (95% confidence interval, 9.0%-18.2%) at the end of 2017 (P = .001) in response to the BRIDGE trial. Use of bridging anticoagulation declined similarly among atrial fibrillation patients at low risk for stroke (29.0% to 14.4%) and intermediate or high risk for stroke (38.0%-20.3%). Younger age and a prior history of stroke were independent predictors of bridging anticoagulation use following the BRIDGE trial publication. The BRIDGE trial publication is associated with a rapid and significant decline in the use of periprocedural bridging anticoagulation.

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 (MAQI

Background Outpatient anticoagulation clinics were initially developed to care for patients taking vitamin K antagonists such as warfarin. There has not been a systematic evaluation of the barriers and facilitators to integrating direct oral anticoagulant (DOAC) care into outpatient anticoagulation clinics. Methods We performed a mixed methods study consisting of an online survey of anticoagulation clinic providers and semi‐structured interviews with anticoagulation clinic leaders and managers between March and May of 2017. Interviews were transcribed and coded, exploring for themes around barriers and facilitators to DOAC care within anticoagulation clinics. Survey questions pertaining to the specific themes identified in the interviews were analyzed using summary statistics. Results Survey responses were collected from 159 unique anticoagulation clinics and 20 semi‐structured interviews were conducted. Three primary barriers to DOAC care in the anticoagulation clinic were described by the interviewees: (a) a lack of provider awareness for ongoing monitoring and services provided by the anticoagulation clinic; (b) financial challenges to providing care to DOAC patients in an anticoagulation clinic model; and (c) clinical knowledge versus scope of care by the anticoagulation staff. These themes linked to three key areas of variation, including: (a) the size and hospital affiliation of the anticoagulation clinic; (b) the use of face‐to‐face versus telephone‐based care; and (c) the use of nurses or pharmacists in the anticoagulation clinic. Conclusions Anticoagulation clinics in the United States experience important barriers to integrating DOAC care. These barriers vary based on the clinic size, model for warfarin care, and staff credentials (nursing or pharmacy).

Many anticoagulation clinics have adapted their services to provide care for patients taking direct oral anticoagulants (DOAC) in addition to traditional warfarin management. Anticoagulation clinic scope of service and operations in this transitional environment have not been well described in the literature. A survey was conducted of United States-based Anticoagulation Forum members to inquire about anticoagulation clinic structure, function, and services provided. Survey responses are reported using summary or non-parametric statistics, when appropriate. Unique clinic survey responses were received from 159 anticoagulation clinics. Clinic structure and staffing are highly variable, with approximately half of clinics (52%) providing DOAC-focused care in addition to traditional warfarin-focused care. Of those clinics managing DOAC patients, this accounts for only 10% of their clinic volume. These clinics commonly have a DOAC follow up protocol (75%). Clinics assign a median of 190.5 (interquartile range 50–300) patients per staff full-time-equivalent, with more patients assigned in phone-based care clinics than in face-to-face based care clinics. Most clinics (68.5%) report receiving reimbursement, which occur either through a combination of patient and insurance provider billing (78.2%), insurance reimbursement only (19.5%) or patient reimbursement only (2.3%). There is wide heterogeneity in anticoagulation clinic structure, function, and services provided. Half of all survey-responding anticoagulation clinics provide care for DOAC-treated patients. Understanding how changes in healthcare policy and reimbursement have impacted these clinics remains to be explored.

Background The impact on health‐care costs and utilization of a single out‐of‐range (OOR) INR value not associated with bleeding or thromboembolic complication among chronic warfarin‐treated patients is not well described. Methods At four large phone‐based anticoagulation clinics (total 14 948 patients), warfarin‐treated patients with atrial fibrillation (AF) or venous thromboembolism were retrospectively propensity matched into an OOR INR group (n = 116) and a control group (n = 58). Types and frequency of contacts (eg, phone, voicemail, facsimile) and personnel involved were identified. A prospective time study analysis of 59 OOR and 92 control patients was performed over 8.5 days to record the time required to care for these patients. 2016 USD cost estimates were generated from average salaries. Results OOR and in‐range INR patients experienced an average of 4.2 and 3.2 (P

Clinical factors and patient preferences are important for selecting oral anticoagulants for venous thromboembolism (VTE) and atrial fibrillation (AF). The relative association of sociodemographic factors with anticoagulant use is unknown. We evaluated a prospective cohort to compare sociodemographic variables in patients who continued on warfarin for AF or VTE to those who transitioned to 1 of the direct oral anticoagulants (DOACs). Adult patients, newly started on warfarin, were enrolled through 6 anticoagulation clinics across Michigan. Of 8468 patients, 53.3% had AF, 45.6% had VTE, and 1.1% had both. Of these, 696 (8.2%) switched from warfarin to a DOAC. There were no significant differences between switchers and nonswitchers for percentage of time with a therapeutic international normalized ratio on warfarin, urban-rural residence status, or health insurance. Switchers were more often white (83.3% vs 77.7%; P < .001), partnered (67.3% vs 59.2%; P < .001), or resided in a zip code with a higher median household income (P < .001). The results show that sociodemographic factors, such as race, partnered status, and income are associated with a patient's likelihood of switching to a DOAC vs remaining on warfarin therapy. Although clinical factors predominate, the reason for, and impact of, these observed variations in care requires further investigation.

It has been suggested that direct oral anticoagulants are being preferentially used in low risk atrial fibrillation (AF) patients. Understanding the changing risk profile of new AF patients treated with warfarin is important for interpreting the quality of warfarin delivery through an anticoagulation clinic. Six anticoagulation clinics participating in the Michigan Anticoagulation Quality Improvement Initiative enrolled 1293 AF patients between 2010 and 2014 as an inception cohort. Abstracted data included demographics, comorbidities, medication use and all INR values. Risk scores including CHADS2, CHA2DS2-VASc, HAS-BLED, SAMe-TT2R2, and Charlson comorbidity index (CCI) were calculated for each patient at the time of warfarin initiation. The quality of anticoagulation was assessed using the Rosendaal time in the therapeutic range (TTR) during the first 6 months of treatment. Between 2010 and 2014, patients initiating warfarin therapy for AF had an increasing mean CHADS2 (2.0 ± 1.1 to 2.2 ± 1.4, p = 0.02) and CCI (4.7 ± 1.8 to 5.1 ± 2.0, p = 0.03), and a trend towards increasing mean CHA2DS2-VASc, HAS-BLED, and SAMe-TT2R2 scores. The actual TTR remained unchanged over the study period (62.6 ± 18.2 to 62.7 ± 17.0, p = 0.98), and the number of INR checks did not change (18.9 ± 5.2 to 18.5 ± 5.1, p = 0.06). Between 2010 and 2014, AF patients newly starting warfarin had mild increases in risk for stroke and death with sustained quality of warfarin therapy.

Importance The prevalence of intracranial aneurysm in patients with fibromuscular dysplasia (FMD) is uncertain. Objective To examine the prevalence of intracranial aneurysm in women diagnosed with FMD. Design, Setting, and Participants This cross-sectional study included 669 women with intracranial imaging registered in the US Registry for Fibromuscular Dysplasia, an observational disease-based registry of patients with FMD confirmed by vascular imaging and currently enrolling at 14 participating US academic centers. Registry enrollment began in 2008, and data were abstracted in September 2015. Patients younger than 18 years at the time of FMD diagnosis were excluded. Imaging reports of all patients with reported internal carotid, vertebral, or suspected intracranial artery aneurysms were reviewed. Only saccular or broad-based aneurysms 2 mm or larger in greatest dimension were included. Extradural aneurysms in the internal carotid artery were included; fusiform aneurysms, infundibulae, and vascular segments with uncertainty were excluded. Main Outcomes and Measures Percentage of women with FMD with intracranial imaging who had an intracranial aneurysm. Results Of 1112 female patients in the registry, 669 (60.2%) had undergone intracranial imaging at the time of enrollment (mean [SD] age at enrollment, 55.6 [10.9] years). Of the 669 patients included in the analysis, 86 (12.9%; 95% CI, 10.3%-15.9%) had at least 1 intracranial aneurysm. Of these 86 patients, 25 (53.8%) had more than 1 intracranial aneurysm. Intracranial aneurysms 5 mm or larger occurred in 32 of 74 patients (43.2%), and 24 of 128 intracranial aneurysms (18.8%) were in the posterior communicating or posterior arteries. The presence of intracranial aneurysm did not vary with location of extracranial FMD involvement. A history of smoking was significantly associated with intracranial aneurysm: 42 of 78 patients with intracranial aneurysm (53.8%) had a smoking history vs 163 of 564 patients without intracranial aneurysm (28.9%; P Conclusions and Relevance The prevalence of intracranial aneurysm in women diagnosed with FMD is significantly higher than reported in the general population. Although the clinical benefit of screening for intracranial aneurysm in patients with FMD has yet to be proven, these data lend support to the recommendation that all patients with FMD undergo intracranial imaging if not already performed.

Background: The impact on healthcare utilization of a single out of range (OOR) INR value not associated with any bleeding or thromboembolic complication among chronic warfarin-treated patients is not well described. Methods: At four large phone-based anticoagulation clinics in Michigan, warfarin-treated patients with atrial fibrillation (AF) or venous thromboembolism (VTE) were identified and data collected via medical chart abstraction. Propensity score matching was used to identify two groups closely matched on patient characteristics: the OOR INR group (INR value < 1.8 or > 3.2 if target range was 2-3) and the control group (INR value between 1.8 and 3.2). Data for each anticoagulation clinic interaction and INR lab test were abstracted until the patient had 2 subsequent and sequential in-range INR values. Methods and frequency of interactions between the anticoagulation clinic and patient were recorded, described as median and interquartile ranges (IQR) and compared using Poisson regression with adjusted means. Results: Demographics were similar for the 116 OOR INR patients and the 58 control patients studied (mean±SD age 72.1±13.0 and 74.3±11.3 years, respectively). Indications for warfarin were more commonly venous thromboembolism in the OOR versus in-range patients (42.2% vs. 27.6%, p=0.06). OOR and in-range INR patients experienced a median of 3 (IQR 3-5) and 3 (IQR 3-3) with adjusted means of 4.2 and 3.2 (p Conclusions: Warfarin-treated patients who experience OOR INR values without any bleeding or thromboembolic complication require more frequent interactions with the anticoagulation clinic, including more telephone calls and multiple types of contact.

Introduction Guidelines recommend the assessment of stroke and bleeding risk before initiating warfarin anticoagulation in patients with atrial fibrillation. Many of the elements used to predict stroke also overlap with bleeding risk in atrial fibrillation patients and it is tempting to use stroke risk scores to efficiently estimate bleeding risk. Comparison of stroke risk scores to bleeding risk scores to predict bleeding has not been thoroughly assessed. Methods 2600 patients followed at seven anticoagulation clinics were followed from October 2009-May 2013. Five risk models (CHADS2, CHA2DS2-VASc, HEMORR2HAGES, HAS-BLED and ATRIA) were retrospectively applied to each patient. The primary outcome was the first major bleeding event. Area under the ROC curves were compared with C statistic and net reclassification improvement (NRI) analysis was performed. Results 110 patients experienced a major bleeding event in 2581.6 patient-years (4.5%/year). Mean follow up was 1.0 ± 0.8 years. All of the formal bleeding risk scores had a modest predictive value for first major bleeding events (C statistic 0.66-0.69), performing better than CHADS2 and CHA2DS2-VASc scores (C statistic difference 0.10 - 0.16). NRI analysis demonstrated a 52-69% and 47-64% improvement of the formal bleeding risk scores over the CHADS2 score and CHA2DS2-VASc score, respectively. Conclusions The CHADS2 and CHA2DS2-VASc scores did not perform as well as formal bleeding risk scores for prediction of major bleeding in non-valvular atrial fibrillation patients treated with warfarin. All three bleeding risk scores (HAS-BLED, ATRIA and HEMORR2HAGES) performed moderately well.

Introduction: For warfarin-treated patients with atrial fibrillation (AF) or venous thromboembolism (VTE), concomitant use of aspirin and warfarin increases the risk of major bleeding 1.5-1.8 fold without an apparent reduction in thrombotic events when there is no clear indication for combination therapy. As a result, each of six anticoagulation clinics in the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) consortium implemented a common intervention between late 2017 and mid 2018 aiming to reduce inappropriate aspirin use. The intervention consisted of a screening process to identify possible inappropriate aspirin use and then contacting the patient's provider to discuss the need for ongoing aspirin therapy. Site-level implementation variation included the personnel carrying out the intervention, the use of technology, and the means of provider communication. Treatment decisions were deferred to the treating provider but facilitated by the anticoagulation clinic staff. We sought to assess the impact of this intervention on the rate of inappropriate aspirin use over time and compare patient characteristics based on aspirin use post intervention. Methods: First, we compared the overall rate of inappropriate aspirin use among the six center MAQI2 anticoagulation clinic cohort immediately before and after the intervention. All patients in MAQI2 were treated with warfarin. Then, we identified a sub-cohort of warfarin-treated patients with AF and/or VTE enrolled between January 2010 to June 2019. Within that sub-cohort, we assessed aspirin use pre and post the site-specific date of implementation of the intervention. Patients with a potential indication for aspirin use were excluded (e.g., any history of coronary artery disease, myocardial infarction, percutaneous coronary intervention, mechanical heart valve replacement, left ventricular assist device placement, peripheral arterial disease, or coronary artery bypass grafting). Each site was able to further restrict who was targeted for intervention (for example, excluding patients with a history of antiphospholipid syndrome or stroke). Using site specific definitions for inappropriate aspirin use we identified four groups at the end of the study period: 1) patients not on aspirin, 2) aspirin-using patients without an apparent indication who stopped aspirin following implementation, 3) aspirin-using patients without an apparent indication who remained on aspirin following implementation, and 4) aspirin-using patients who developed an indication for aspirin during the study period. To assess inappropriate aspirin use in our cohort, the characteristics of the first three groups were compared. Results: Between August 2017 and May 2019, a total of 3,766 warfarin-treated patients enrolled in MAQI2. Following implementation, inappropriate aspirin use was reduced by 34% (from 27.9% [401/1437] to 18.5% [251/1356]). A sub-cohort of 1,007 patients who met the inclusion criteria had clinical follow-up pre and post intervention and were followed for an average of 40.1 months from enrollment to their first follow-up post-intervention. Of this sub-cohort, 226 (22.4%) were inappropriately on aspirin, with 50 (22.1%) stopping aspirin. A small number of patients 37 (3.7%) developed an indication for aspirin (e.g., myocardial infarction) during the study period and were removed from this analysis. As compared to patients not taking aspirin, patients on inappropriate aspirin were more often taking warfarin for AF, had congestive heart failure, chronic kidney disease, diabetes mellitus, hypertension, and had a higher Charlson Comorbidity index; they were less likely to have VTE or a history of VTE. As compared to patients continuing on aspirin following implementation, patients stopping inappropriate aspirin were more likely to have chronic kidney disease (p=0.02) or a history of falls (p=0.03). Conclusion: Among warfarin-treated patients with AF or VTE, inappropriate aspirin usage can be identified and significantly reduced using a simple intervention in the anticoagulation clinic. Patients at higher risk of bleeding may be more likely to have their aspirin discontinued. Further studies are needed to see if reducing inappropriate aspirin usage translates to improved clinical outcomes and to determine the reasons for patient persistence on inappropriate aspirin. Disclosures Kaatz: Janssen: Honoraria, Research Funding; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria; Portola: Honoraria. Kline-Rogers:AC Forum: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; QUANTUM-AF: Membership on an entity's Board of Directors or advisory committees. Sood:Bayer: Research Funding. Froehlich:Blue Cross Blue Shield of Michigan: Research Funding; Novartis: Honoraria; Boehringer-Ingelheim: Honoraria; Fibromuscular Dysplasia Society: Research Funding; Merck: Honoraria; Pfizer: Honoraria; Janssen: Honoraria. Barnes:Portola: Honoraria; Pfizer/Bristol Myers Squib: Research Funding; Pfizer: Honoraria; AMAG Pharmaceuticals: Honoraria; Bristol Myers Squib: Honoraria; Blue Cross Blue Shield of Michigan: Research Funding; Janssen: Honoraria.

To more accurately quantify the proportion of anticoagulated patients with atrial fibrillation (AF) that may be inappropriately treated with warfarin for stroke prevention. Patients with AF have an increased risk of stroke, which is lowered by the use of warfarin. However there is likely more potential harm than benefit in patients that do not have additional stroke risk factors. Studies have described overuse of warfarin for stroke prophylaxis in lowest risk patients. However, many of those studies did not assess for electrical cardioversion (ECV) or radiofrequency ablation (RFA) as indications for warfarin therapy. Data from 1852 non-valvular AF patients treated with warfarin between October 2009 and October 2011 at seven anticoagulation centers participating in the Michigan Anticoagulation Quality Improvement Initiative registry were analyzed. Low risk AF patients were risk stratified using the CHADS2 scoring systems, with a score of zero representing lowest risk. 193 (10.4 %) of AF patients receiving warfarin were identified as having the lowest risk of stroke by the CHADS2 score. Of the patients with CHADS2 = 0, 130 (67.4 %) had undergone a recent ECV and/or RFA. Of all AF patients, only 63 (3.4 %) had a CHADS2 score of 0 and no recent ECV or RFA. The vast majority of AF patients receiving anticoagulation in this multi-center registry are doing so in accordance with national and international guidelines. In contrast to prior population-based studies, very few low risk patients are receiving inappropriate warfarin therapy for stroke prophylaxis in AF, when procedure-based indications are also considered.

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.