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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.

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.

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

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

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.

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.

Background— Fibromuscular dysplasia (FMD), a noninflammatory disease of medium-size arteries, may lead to stenosis, occlusion, dissection, and/or aneurysm. There has been little progress in understanding the epidemiology, pathogenesis, and outcomes since its first description in 1938. Methods and Results— Clinical features, presenting symptoms, and vascular events are reviewed for the first 447 patients enrolled in a national FMD registry from 9 US sites. Vascular beds were imaged selectively based on clinical presentation and local practice. The majority of patients were female (91%) with a mean age at diagnosis of 51.9 (SD 13.4 years; range, 5–83 years). Hypertension, headache, and pulsatile tinnitus were the most common presenting symptoms of the disease. Self-reported family history of stroke (53.5%), aneurysm (23.5%), and sudden death (19.8%) were common, but FMD in first- or second-degree relatives was reported only in 7.3%. FMD was identified in the renal artery in 294 patients, extracranial carotid arteries in 251 patients, and vertebral arteries in 82 patients. A past or presenting history of vascular events were common: 19.2% of patients had a transient ischemic attack or stroke, 19.7% had experienced arterial dissection(s), and 17% of patients had an aneurysm(s). The most frequent indications for therapy were hypertension, aneurysm, and dissection. Conclusions— In this registry, FMD occurred primarily in middle-aged women, although it presents across the lifespan. Cerebrovascular FMD occurred as frequently as renal FMD. Although a significant proportion of FMD patients may present with a serious vascular event, many present with nonspecific symptoms and a subsequent delay in diagnosis.

IMPORTANCE: Fibromuscular dysplasia (FMD) is a nonatherosclerotic arterial disease that predominately affects women and is most commonly diagnosed in middle age. The natural history of FMD among patients diagnosed at an older age is not well understood. OBJECTIVE: To examine the differences in clinical presentation, arterial bed involvement, vascular events, and need for vascular procedures between younger and older patients with FMD. DESIGN, SETTING, AND PARTICIPANTS: Analysis of baseline data for patients enrolled in the US Registry for FMD as of December 15, 2016, at referral centers participating in the US Registry for FMD. Patients 18 years and older at the time of enrollment and those with only confirmed multifocal (string of beads type) FMD were included. Patients were categorized according to age at the time of diagnosis (≥65 years vs

Fibromuscular dysplasia (FMD), a non-inflammatory arterial disease, may lead to renovascular hypertension (HTN) and cerebrovascular disease. Little is known about medication use in FMD. Clinical features and medication use were reviewed in a national FMD registry (12 US sites). Medication usage was assessed in raw and adjusted analyses. Covariates included demographic characteristics, co-morbid conditions and vascular bed involvement. A total of 874 subjects (93.6% female) were included in the analysis. Mean age was 55.6±13.1 years, 74.5% had HTN, 25.4% had a history of transient ischemic attack or stroke, and 7.5% had a history of coronary artery disease (CAD). Renal and cerebrovascular arteries were affected in 70.4% and 74.7%, respectively. Anti-platelet agents were administered to 72.9% of patients. In multivariate analyses, factors associated with a greater likelihood of anti-platelet agent use were older age (OR=1.02 per year, p=0.005), CAD (OR=3.76, p=0.015), cerebrovascular artery FMD involvement in isolation (OR=2.31, p

To the Editor: Fibromuscular dysplasia (FMD) is an uncommon arteriopathy which can result in stenosis, aneurysm, dissection, and/or occlusion of arteries. It most commonly affects the renal, extracranial carotid, and vertebral arteries but can affect any artery. Although FMD occurs primarily in

The pathophysiology of fibromuscular dysplasia (FMD) is unknown; however, smoking has been implicated as a potential contributing factor [(1,2)][1]. Prior studies have shown a higher prevalence of smoking among those with renal FMD compared with matched hypertensive control subjects [(3)][2]. The

Background— The purpose of this study was to assess whether delayed enhancement (DE) on MRI is associated with ventricular tachycardia (VT)/ventricular fibrillation or death in patients with cardiac sarcoidosis and left ventricular ejection fraction >35%. Methods and Results— Fifty-one patients with cardiac sarcoidosis and left ventricular ejection fraction >35% underwent DE-MRI. DE was assessed by visual scoring and quantified with the full-width at half-maximum method. The patients were followed for 48.0±20.2 months. Twenty-two of 51 patients (63%) had DE. Forty patients had no prior history of VT (primary prevention cohort). Among those, 3 patients developed VT and 2 patients died. DE was associated with risk of VT/ventricular fibrillation or death ( P =0.0032 for any DE and P Conclusions— RV DE in patients with cardiac sarcoidosis is associated with a risk of adverse events in patients with cardiac sarcoidosis and preserved ejection fraction in the absence of a prior history of VT. Patients with DE and a prior history of VT have a high VT recurrence rate. Patients without DE on MRI have a low risk of VT.

Fibromuscular Dysplasia (FMD) is an arteriopathy which may lead to stenosis, aneurysm, and dissection. Pulsatile tinnitus (PT) is a common, debilitating symptom of FMD. Data were queried from the United States Registry for FMD from 11 clinical centers. Of the 873 patients (pts) enrolled, data

Introduction: The regulatory approval and growing clinical acceptance of the direct oral anticoagulants (DOACs: apixaban, dabigatran, edoxaban, and rivaroxaban) has challenged warfarin as the mainstay of anticoagulation for the management of venous thromboembolic disease (VTE: deep vein thrombosis and pulmonary embolism) and atrial fibrillation/flutter (Afib). As clinicians and patients choose from the expanded menu of oral anticoagulant options, it is unknown how socioeconomic variables like income, race, gender, health insurance, or marital status may influence which anticoagulant a patient utilizes. We sought to explore if patients who stayed on warfarin differed from those who changed to a DOAC, with regard to the aforementioned socioeconomic variables. Furthermore, we desired to assess how the clinical variable of INR management, as reflected by the percent of time in therapeutic range (TTR), compared between these two groups. Methods: The Michigan Anticoagulation Quality Improvement Initiative (MAQI2) is a multi-center collaborative registry of 6 active anticoagulation clinics across Michigan. Patients newly initiating warfarin for Afib or VTE between October 2009 and July 2016 were included. Enrollees who remained on warfarin in follow-up ("non-switchers") were compared to those that transitioned to a DOAC ("switchers") on the basis of demographics, TTR by linear interpolation, race, marital status, and insurance. Patients in each group were further analyzed in quartiles based on the median household income of their zip code of residence, derived from the 2014 U.S. Census Bureau's American Community Survey. Analyses were performed using Student's t-tests and Wilcoxon Rank-sum tests for continuous variables, and chi-square and Fisher's exact tests for categorical variables. Results: 8,480 patients met the inclusion criteria, 54.4% with Afib, 45.6% with VTE, and 1.1% with both; out of this group, 675 (8%) switched from warfarin to a DOAC. There were no significant differences between switchers and non-switchers for age (mean 68.1±13.6 and 67.4±15.7, p=0.23), gender (53.9% vs. 51.5% male, p=0.23), percent TTR on warfarin (55.1% vs. 56.9%, p=0.056), or percent with commercial health insurance (33.9% vs. 34.4%, p=0.78) or uninsured (0.3% vs. 0.9%, p=0.17). Patients were more likely to switch to DOAC therapy if they had Afib vs. VTE (10.9% vs. 4.5%, p Conclusion: While DOACs are often considered in patients who have difficulty maintaining a therapeutic INR, TTR was not predictive of changing from warfarin to a DOAC in this population. However, we found that SES factors, such as race, insurance status and income are associated with a patient's likelihood for switching to DOAC therapy vs. remaining on warfarin therapy. Further investigation into the reason for, and clinical impact of, these observed disparities in the care of our patients is needed. Table Table. Disclosures Sood: Bayer: Research Funding. Kline-Rogers:Janssen: Consultancy; ACP: Consultancy; AC Forum: Membership on an entity's Board of Directors or advisory committees. Almany:Abbott: Research Funding; Kona: Consultancy; Trice Orthopedics: Consultancy; MiCardia: Consultancy; Biostar Ventures: Equity Ownership; Ablative Solutions: Equity Ownership; Boston Scientific: Research Funding. Kaatz:Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; Daiichi Sankyo: Consultancy; Janssen: Consultancy; Boehringer Ingelheim: Consultancy; Boehringer Ingelheim: Honoraria; Janssen: Honoraria; Bristol Myer Squibb: Honoraria; Pfizer: Honoraria; CSL Behring: Honoraria. Froehlich:Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees; Fibromuscular Disease Society of America: Research Funding; Blue Cross/Blue Shield of Michigan: Research Funding; Novartis: Consultancy; Janssen: Consultancy; Merck: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees. Barnes:Portolal: Consultancy; Blue Cross Blue Shield of Michigan: Research Funding; Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding.

Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are associated with high rates of venous thromboembolism (VTE). Anticoagulants, such as warfarin, are commonly used to prevent VTE in such patients. The practice and effectiveness of warfarin in real world populations is not well documented. 595 TKA and THA patients treated with warfarin were followed by two anticoagulation clinics in the Michigan Anticoagulation Quality Improvement Initiative. Length of prescribed anticoagulation, percent time in therapeutic range (%TTR) and time to first therapeutic INR were calculated for each surgical group. For THA, all 300 patients received at least ten days with a 28-day median length of anticoagulation therapy. For TKA, all 295 patients received at least 10 days with a 28-day median length of anticoagulation therapy. For THA patients, time to first therapeutic INR was on average 12.0 ± 8.0 days with a mean %TTR of 36.6 ± 26.8 % for goal INR 2.0–3.0. For THA patients, 39 (13 %) never reached target INR. For TKA patients, time to first therapeutic INR was on average 12.8 ± 10.3 days with a mean %TTR of 36.0 ± 28.3 % for goal INR 2.0–3.0. For TKA patients, 44 (14.9 %) never reached target INR. Many orthopaedic surgeons who use warfarin for post-arthroplasty VTE prophylaxis do so in accordance with national guidelines. The time to first therapeutic INR is strikingly long and %TTR markedly low for these patients, raising questions about the efficacy of warfarin therapy in the first 1–2 post-operative weeks. Further studies to investigate the best target INR for warfarin prophylaxis, as well as the composite rates of VTE and clinically relevant bleeding from treatment with warfarin, LMWH and newer anticoagulants are needed.

Results: Mean age at the time of enrollment was 55.7 +13.1 years (range 18-86 years) and 91% of pts were female. Mean BMI was 25.5 + 5.2 kg/ m2 and 48.8% of patients had a BMI > 25 kg/m2. Mean blood pressure on enrollment was 130/75 + 20/12.4 mmHg and 77.9% of pts were taking at least one blood pressure medication. 60% of pts reported significant headaches and 27.5% had pulsatile tinnitus. A cervical or epigastric bruit was a presenting sign that led to FMD diagnosis in 22.2% and 9.4% of pts, respectively. A neurological and vascular PE was recorded at the time of enrollment in 92.6% (414/447). Findings suggestive of Horner’s syndrome (pupil abnormality or ptosis) were reported in 12.4% of pts. Cranial nerve abnormalities were reported in 9.4% and other focal neurological deficits were reported in 13.6%. Bruits were reported over the carotid arteries (30.5%; 18.1% bilateral), epigastrium (17.5%), and flanks (6.1%; 3.2% bilateral). Among pts with reported imaging of the extracranial circulation (carotid and vertebral) and a documented PE, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of carotid bruit in predicting extracranial carotid FMD were 45.4%, 93.7%, 95.4%, and 37.4%, respectively. The sensitivity, specificity, PPV and NPV of epigastric and/or flank bruit in predicting renal and/or mesenteric FMD were 24.0%, 93.3%, 92.6%, and 26.0%, respectively.

Results: Among pts with renal artery involvement alone, ultrasound (US) was the most common initial diagnostic modality (77%), followed by catheter-based angiography (66.7%), CT angiography (39.7%), MR angiography (21.4%), and intravascular US (5.6%). Among pts with extracranial carotid or vertebral alone, US remained the most commonly used imaging modality (79.2%); with fewer pts undergoing catheter-based angiography (37.5%). Pts with both renal and extracranial carotid/vertebral involvement underwent more imaging overall, with US (83.8%) and catheter-based angiography (64.1%) the most common. At follow-up, US remained the most common in pts with renal involvement alone (72.3%), extracranial carotid/vertebral alone (86.2%), or both (77.1%). Catheter-based angiography was common for renal alone (38.3%), extracranial carotid/vertebral alone (20.7%), or both (40%). 74.5% of pts with renal FMD underwent carotid/vertebral artery imaging; 83.7% of pts with carotid/vertebral FMD had renal artery imaging. Of pts diagnosed with extracranial carotid FMD, 63.7% also had imaging of the intracranial vasculature.

Background Performing preoperative coronary angiography (CA) before surgical repair of a type A acute aortic dissection (TA-AAD) remains controversial. Although the information provided by CA may be useful in planning the surgical approach, the potential delay to surgery and complications of CA may confer added risk of death before definitive repair of the aorta. Methods We analyzed 1,343 patients from January 27, 1996, to May 3, 2010, with TA-AAD from the International Registry of Acute Aortic Dissection who underwent surgical or endovascular repair during the index hospitalization, with (n = 156) or without (n = 1,187) preoperative CA. The main outcomes measured were in-hospital complications and in-hospital and long-term mortality. Results Patients who underwent preoperative CA were more likely to have a history of atherosclerosis and present with electrocardiographic signs of myocardial ischemia/infarction. In the preoperative CA group, significant delays from the onset of symptoms to the time of surgery occurred. In-hospital postoperative complications and mortality rates were largely similar between the 2 groups. On multivariable logistic regression analysis, preoperative CA had no significant effect on in-hospital risk-adjusted mortality when compared to the validated International Registry of Acute Aortic Dissection risk score. Long-term mortality was similar between patients receiving preoperative CA and those who did not; long-term rehospitalization rates were higher, although largely insignificantly, among preoperative CA recipients through 5 years of follow-up. Conclusions Preoperative CA is infrequently performed on patients with TA-AAD, except, occasionally, on patients at high risk for myocardial ischemia. When performed, preoperative CA was not associated with any significant changes in in-hospital and long-term mortality.

The clinical phenotype and prognosis in Fibromuscular Dysplasia (FMD) patients (pts) with Dissection (D) and Aneurysm (A) are poorly defined. Clinical features, locations and therapeutic procedures were reviewed in 732 pts enrolled in the United States Registry for FMD. Aneurysm (A) was present in