ADVERSE EVENTS IN LOW VERSUS NORMAL BODY WEIGHT PATIENTS PRESCRIBED APIXABAN OR RIVAROXABAN FOR ATRIAL FIBRILLATION

Background: Clinical trials comparing direct oral anticoagulants (DOACs) to warfarin included only a small number of patients that weighed less than 60 kilograms (kg). The safety and efficacy of DOACs in low weight adult patients with atrial fibrillation (AF) is still unclear. Published data is not only sparse but have mixed outcomes. Therapy with DOACs may increase bleeding and/or clotting risk with uncertain antithrombotic benefit in low weight patients. Objective: To assess bleeding and thrombotic event rates for patients with AF that are prescribed a DOAC and have a low body weight (less than 60 kg) versus patients that have a normal body weight (60 to 100 kg). Methods: Within the Michigan Anticoagulation Quality Improvement Initiative (MAQI2), we analyzed data for patients with AF prescribed apixaban or rivaroxaban from 2017 through 2021 who had at least 12 months of follow-up. Patients were excluded if they were prescribed dosing different from package insert instructions. Patients were divided by weight into low (less than 60 kg) and normal (60 to 100 kg) cohorts. Assessments included rates of thrombotic events, major bleeding events (International Society on Thrombosis and Haemostasis [ISTH]), and non-major bleeding events requiring an Emergency Department (ED) visit. Patient characteristics were compared using Chi-square and t-test. Bleeding event rates were adjusted for age, gender, and diabetes mellitus and thrombotic event rates were adjusted by CHA2DS2-VASc score. Poisson regression was used to estimate adjusted adverse event rates to control for potentially confounding covariates (apixaban only due to few patients prescribed rivaroxaban). Results: A total of 616 patients met the inclusion criteria: 83 (13.5%) low weight and 533 (86.5%) normal weight. Most patients were prescribed apixaban (88.5%) with the low weight cohort more often prescribed the lower dose of apixaban (55% versus 6.2%, p\u3c0.0001). The low weight cohort had a higher mean age (78.9% versus 74.4%, p\u3c0.0002), proportion of females (94% versus 54%, p\u3c0.0001) and CHA2DS2-VASc score (4.4 (1.6) versus 3.9 (1.6)), but a lower proportion of patients with diabetes mellitus (9.6% versus 25.1%, p\u3c0.0018) [Table 1]. In the unadjusted analysis of patients prescribed apixaban, non-major bleeding events requiring an ED visit (10.8 per 100 patient-years versus 7.4 per 100 patient-years, p\u3c0.0001), occurred more often in the low versus normal weight patient cohort [Table 2]. However, adjusted analysis found no statistically significant difference in events in low and normal weight cohorts prescribed apixaban [Table 2]. Comparisons within patients prescribed rivaroxaban could not be made due to a small sample size of low weight patients. Conclusions: Among low weight patients with AF the use of apixaban was not associated with bleeding (major and non-major) or thrombotic events after adjusting for potential confounding covariates. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in these patients

Comparison of Patient Outcomes Before and After Switching From Warfarin to a Direct Oral Anticoagulant Based on Time in Therapeutic Range Guideline Recommendations

This cohort study evaluates stroke and major bleeding rates before and after switching from warfarin to a direct oral anticoagulant (DOAC) in patients grouped by pre-switch time-in-therapeutic range guideline thresholds

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

Length of Anticoagulation in Provoked Venous Thromboembolism: A Multicenter Study of How Real-World Practice Mirrors Guideline Recommendations

Background For more than a decade, guidelines have recommended a limited 3 months of anticoagulation for the treatment of provoked venous thromboembolism (VTE). How closely real-world practice follows guideline recommendations is not well described. Methods and Results In our multicenter, retrospective cohort study, we evaluated trends in anticoagulation duration for patients enrolled in the MAQI(2) (Michigan Anticoagulation Quality Improvement Initiative) registry who were receiving anticoagulation for a provoked VTE. The MAQI(2) registry comprises 6 centers in Michigan that manage patients\u27 long-term anticoagulation. We identified 474 patients on warfarin and 302 patients on direct oral anticoagulants who were receiving anticoagulation for a primary indication of provoked VTE between 2008 and 2020. Using a predefined threshold of 120 days (3 months plus a buffer period), predictors of extended anticoagulant use were identified using multivariable logistic regression. Most patients received \u3e120 days of anticoagulation, regardless of which medication was used. The median (25th-75th percentile) length of treatment for patients taking warfarin was 142 (91-234) days and for direct oral anticoagulants was 180 (101-360) days. Recurrent VTE (odds ratio [OR], 2.75 [95% CI, 1.67-4.53]), history of myocardial infarction (OR, 3.92 [95% CI, 1.32-11.7]), and direct oral anticoagulant rather than warfarin use (OR, 2.22 [95% CI, 1.59-3.08]) were independently associated with prolonged anticoagulation. Conclusions In our cohort of patients with provoked VTE, most patients received anticoagulation for longer than the guideline-recommended 3 months. This demonstrates a potential opportunity to improve care delivery and reduce anticoagulant-associated bleeding risk

AREDS Formula, Warfarin, and Bleeding: A Case Report from the Michigan Anticoagulation Quality Improvement Initiative

Importance. The anticoagulant warfarin has been shown to interact with other medications, vitamin K containing foods, and over-the-counter products. These interactions may inhibit or potentiate the effect of warfarin, resulting in serious clotting or bleeding events. Observations. We report the case of an 84-year-old woman with atrial fibrillation, prescribed warfarin in May 2010 for stroke prevention. Her international normalized ratio (INR) was stable until April 2013, when she was prescribed AREDS (Age Related Eye Disease Study) formula pills, an eye vitamin compound, to slow the progression of age-related macular degeneration. This change was not reported to the Anticoagulation Service. Eighteen days later, she presented to the ED with groin and back pain and an INR of 10.4. An abdominal CT revealed a retroperitoneal hemorrhage with extension in multiple muscles. Both warfarin and AREDS were discontinued and the patient was discharged to subacute rehabilitation. This case was reviewed by the Anticoagulation Service and actions were taken to prevent similar adverse events. Conclusions. This report provides an example of the potential danger of supplement use, in this case, AREDS formula, in patients prescribed warfarin, and the importance of communicating medication changes to the providers responsible for warfarin management

Disparities in risk perception of thyroid cancer recurrence and death

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154276/1/cncr32670.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154276/2/cncr32670_am.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