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

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

Guidelines and experts note that patients with atrial fibrillation require regular renal function monitoring to ensure safe use of direct oral anticoagulants (DOACs). Insufficient monitoring could lead to inappropriate dosing and adverse events. Our objective was to describe the frequency of insufficient creatinine monitoring among patients on DOACs, and to describe clinical factors associated with insufficient monitoring. We hypothesized that renal impairment would be associated with insufficient monitoring. A retrospective cohort study was performed with data from the Michigan Anticoagulant Quality Improvement Initiative. Patients were included if they initiated DOAC therapy for stroke prevention related to atrial fibrillation, remained on therapy for ≥ 1 year, and had baseline creatinine and weight measurements. Creatinine clearance (CrCl) was calculated via Cockcroft-Gault equation. Our outcome was the presence of insufficient creatinine monitoring, defined as: \u3c 1 creatinine level/year for patients with CrCl \u3e 50, or \u3c 2 creatinine levels/year for patients with CrCl ≤ 50. Multivariable analysis was done via logistic regression. Study population included 511 patients. In overall, 14.0% of patients received insufficient monitoring. Among patients with CrCl \u3e 50, 11.5% had \u3c 1 creatinine level/year. Among patients with CrCl ≤ 50, 27.1% received \u3c 2 creatinine levels/year. Baseline renal dysfunction was associated with a higher likelihood of insufficient creatinine monitoring (adjusted odds ratio 3.64, 95% confidence interval 1.81-7.29). This shows a significant gap in the monitoring of patients on DOACs-patients with renal impairment are already at higher risk for adverse events. Future studies are needed to describe the barriers in monitoring these patients and to identify how to optimally address them

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

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

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

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

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

Safety and efficacy of direct oral anticoagulants (DOAC) in low weight patients with atrial fibrillation (AF) is unclear due to few low body weight patients enrolled in clinical trials. To assess bleeding and thrombotic event rates for patients with AF that are prescribed apixaban and have a low versus normal body weight. We analyzed patients with AF prescribed apixaban from 2017 to 2020 with at least 12 months of follow-up. Patients were divided into low [\u3c 60 kg (kg)] and normal (60-100 kg) weight cohorts. Bleeding and thrombotic event rates were compared. Poisson regression and Cox proportional hazard models were used to estimate adjusted adverse event rates. A total of 545 patients met inclusion criteria. In the unadjusted analysis, there was an increase in non-major bleeding events requiring an Emergency Department visit more often in the low versus normal weight cohort (10.8 versus 7.4 per 100 patient-years, p = 0.15). Thrombotic event rates also occurred more often in the lower versus normal weight cohort (2.4 versus 0.9 per 100 patient-years, p = 0.09). However, adjusted analysis found no statistically significant difference in bleeding or thrombotic events between low and normal weight cohorts. The adjusted hazard ratio for bleeding was similar between the two weight cohorts. The use of apixaban in low body weight patients was not associated with higher rates of bleeding or thrombotic events, compared to those with normal body weight, after adjusting for potential confounding covariates. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in these patients