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Thromboembolism is a common and deadly consequence of COVID-19 infection for hospitalized patients. Based on clinical evidence pre-dating the COVID-19 pandemic and early observational reports, expert consensus and guidance documents have strongly encouraged the use of prophylactic anticoagulation for patients hospitalized for COVID-19 infection. More recently, multiple clinical trials and larger observational studies have provided evidence for tailoring the approach to thromboprophylaxis for patients with COVID-19. This document provides updated guidance for the use of anticoagulant therapies in patients with COVID-19 from the Anticoagulation Forum, the leading North American organization of anticoagulation providers. We discuss ambulatory, in-hospital, and post-hospital thromboprophylaxis strategies as well as provide guidance for patients with thrombotic conditions who are considering COVID-19 vaccination.

Evidence suggests that an apixaban-based strategy to treat acute venous thromboembolism (VTE) in patients with End-Stage Kidney Disease (ESKD) may be safer than a warfarin-based strategy. Apixaban has an additional advantage of not requiring bridging with heparin which often necessitates long hospitalizations for patients with ESKD. We sought to determine if an apixaban-based strategy is associated with less healthcare utilization than a warfarin-based strategy.We employed a new-user, active-comparator retrospective cohort study using inverse probability of treatment weights (IPTW) to adjust for confounding demographic and clinical variables. Patients with ESKD newly initiated on either apixaban or warfarin for an acute VTE between 2014 and 2018 in the United States Renal Data System were included. Outcomes were presence of index hospitalization, length of index hospitalization, total hospital days, total hospital days excluding index hospitalization, total emergency department (ED) visits that did not result in hospitalization, and total skilled nursing facility days.At six months, patients who received apixaban were less likely to have an index hospitalization, had a shorter index hospitalization (median of 4.0 vs 8.0 days, p 0.001), and had fewer total hospital days. The IPTW and index year-adjusted incidence rate ratios of total hospital days at one, three, and six months were 0.83 (95 % confidence intervals (CI) 0.79-0.86), 0.84 (95 % CI 0.81-0.88), and 0.88 (95 % CI 0.83-0.92) for apixaban compared to warfarin.Among patients with ESKD and VTE, resource utilization for an apixaban-based strategy appears to be lower than for a warfarin-based strategy.

Patients with end-stage kidney disease (ESKD) are at significantly increased risk for both thrombosis and bleeding relative to those with normal renal function. The optimal therapy of venous thromboembolism (VTE) in patients with ESKD is unknown.To compare the safety and effectiveness of apixaban relative to warfarin in patients with ESKD and acute VTE.New-user, active-comparator retrospective United States population-based cohort with inverse probability of treatment weighting, using the United States Renal Data System data from 2014 to 2018. We included adults with ESKD on hemodialysis or peritoneal dialysis who were newly initiated on apixaban or warfarin for an acute VTE.The coprimary outcomes were major bleeding, recurrent VTE, and all-cause mortality within 6 months of anticoagulant initiation. Secondary outcomes were intracranial hemorrhage and gastrointestinal bleeding. The primary analyses were based on intent-to-treat defined by the first drug received and accounted for competing risks of death. Sensitivity analyses included varied follow-up time, as-treated analyses, and dose-specific apixaban subgroups.The apixaban and warfarin cohorts included 2302 and 9263 patients, respectively. Apixaban was associated with a lower risk of major bleeding (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.70-0.94), intracranial bleeding (HR 0.69, 95% CI 0.48-0.98), and gastrointestinal bleeding (HR 0.82, 95% CI 0.69-0.96). Recurrent VTE and all-cause mortality were not significantly different between the groups.Apixaban was associated with a lower risk of bleeding relative to warfarin when used to treat acute VTE in patients with ESKD on dialysis.

Direct-acting oral anticoagulants (DOACs) are associated with risk of major bleeding. This study evaluated the incremental healthcare economic burden of patients with atrial fibrillation (AF) treated with DOACs and hospitalized with a major bleed (MB).Adult patients with AF treated with DOACs and hospitalized with MB or no MB hospitalizations during January 1, 2015-April 30, 2018 were extracted from MarketScan claims databases. The index date was defined as the first MB hospitalization for patients with MB and a random date during DOAC usage for patients without MB. Healthcare resource utilization and costs were evaluated for index hospitalizations of patients with MB and during the 6-month period prior to index dates and a variable follow-up period of 1-12 months for both patients with and those without MB. Multivariable regression analyses were performed to evaluate the incremental burden of MB vs. non-MB status on all-cause hospital days and healthcare costs.Of the overall AF patient population using DOACs (N = 152,305), 7577 (5.0%) had a hospitalization for MB. Greater proportions of those who had an MB hospitalization were older and female compared to patients without MB (mean age 76.1 vs. 70.1 years; 44.1% vs. 40.5% female, respectively). For index MB hospitalizations, mean length of stay (LOS) was 5.3 days and cost was $32,938. In adjusted analyses, patients with MB had 3.6 more hospital days, $10,609 higher inpatient cost, $9613 higher outpatient medical cost, and $18,910 higher total healthcare costs for all causes per patient during follow-up (all p 0.001). Including index MB hospitalization costs in the follow-up, all-cause total adjusted healthcare costs were almost two times higher for patients with vs. without MB ($96,590 vs. $49,091, p 0.001).Among a large US nationally representative sample of patients with AF treated with DOACs, the cost of MB hospitalization was substantial. Furthermore, healthcare costs following MB events were nearly 40% higher compared to those of patients with AF without an MB.

Introduction Stroke prevention among patients with nonvalvular atrial fibrillation (NVAF) requires careful assessment of both the risk of stroke and bleeding. Hypothesis We hypothesized that in a real-world managed care population of patients with NVAF, bleeding incidence increases with CHADS2 stroke risk. Methods Administrative claims data were used for this retrospective study. Adults with healthcare claims related to AF (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Patients were categorized based on CHADS2 scores of 0, 1, 2, or ≥3, with higher scores indicating more risk factors. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, death, physician guided medical or surgical treatment, or intracranial bleed. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Results The mean (SD) age of the study sample (N=48,260) was 67±13 years and 62% of the patients were male. Mean follow-up duration was 802±540 days (median 673 days). Mean (SD) baseline CHADS2 score was 1.48±1.15. Event rates for each bleeding category increased with increasing CHADS2 scores (Table). Conclusions Patients with NVAF in a real-world managed care setting who had high stroke risk also had a high rate of bleeding events, including major events. Patients at high risk for stroke might require more careful selection of anticoagulation therapy to avoid bleeding events.

Introduction Warfarin discontinuation among real world nonvalvular atrial fibrillation (NVAF) patients is common. Hypothesis We hypothesized that in a managed care population, warfarin discontinuation is associated with increased stroke risk. Methods Patients who initiated warfarin therapy between Jan 2005 and Jun 2009 and had a healthcare claim related to AF within 30 days prior to the first warfarin claim, but no evidence of valvular disease, were included. Warfarin discontinuation was defined as a supply gap of >60 days without evidence of International Normalized Ratio (INR) measurements. Follow-up was divided into periods of warfarin treatment and discontinuation. Stroke events were identified based on claims for inpatient stays with a primary diagnosis for stroke or transient ischemic attack (TIA). Cox proportional hazards models were constructed to assess the relationship between warfarin discontinuation and incident stroke while adjusting for baseline demographics, stroke and bleeding risk, and comorbidities, as well as time-dependent antiplatelet use, stroke, and bleeding events in the prior warfarin treatment period. Results The mean (SD) age of the study sample (N=16,253) was 67±12 years; 64.8% was male. Mean CHADS2 score was 1.84±1.30; mean HAS-BLED score was 2.00±1.18. Half (51.4%) of patients discontinued warfarin therapy at least once and the overall sample had a mean of 1.87 warfarin treatment periods during a mean of 668 days follow-up. Approximately 1186 patients (7%) had a stroke or TIA at any site of service during follow-up. Risk of stroke significantly increased during warfarin discontinuation periods compared with therapy periods (HR 1.60; 95%CI 1.35-1.90; P Conclusions In the real world, over half of patients on anticoagulation therapy had treatment gaps or permanently discontinued therapy. These usage patterns, as well as prior bleeding, were associated with increased stroke risk.

Introduction Bleeding among patients with nonvalvular atrial fibrillation (NVAF) may prevent subsequent anticoagulation, and consequent inadequate stroke prophylaxis could extend the economic impact of bleeding beyond the acute event. Hypothesis We hypothesized that costs for NVAF patients rise acutely following a major bleed and stay elevated through extended follow-up compared with costs for NVAF patients without a major bleed. Methods Adults with healthcare claims related to AF between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Follow-up lasted until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, death, physician guided medical or surgical treatment, or intracranial bleed. Among patients with major bleeding events, average daily costs were calculated in the pre-bleed (from the index date until the event) and post-bleed (from the end of the event until the end of follow-up) periods, and during the event. Among patients without major bleeding events, the average daily cost during the entire follow-up period was calculated. Results Among 48,260 patients with NVAF (mean age 67±13 years; 62% male), 7908 (16%) had a major bleeding event during a mean (SD) follow-up of 802±540 days (median 673 days). Major bleeding events lasted a mean of 15±25 days and averaged $16,830 per event. Among patients who experienced a major event, average costs per patient increased from approximately $50 per day in the pre-bleed period to $63 per day in the post-bleed period, a difference of approximately $13 per day. Daily costs for NVAF patients who did not experience a major bleeding event averaged approximately $36 per day; thus, average daily costs for patients who had a major bleed were greater in both the pre- and post-bleed periods (by $14 per day and $27 per day, respectively) than for patients who did not have a major event. Cost differences persisted 2 years following incident major bleeding events. Conclusions Major bleeding events among NVAF patients are associated with substantial healthcare costs, both directly related to the event and in the post-event period.