Treatment of atrial fibrillation and venous thromboembolism with factor Xa inhibitors in severely obese patients.

A paucity of data exists to support the use of factor (F)Xa inhibitors in severely obese patients with a weight of ≥150 kg or body mass index (BMI) of ≥50 kg/m2. The purpose of this study was to evaluate whether FXa inhibitors are as safe and effective as warfarin for the treatment of atrial fibrillation (AF) and/or venous thromboembolism (VTE) in individuals with a BMI of ≥50 kg/m2 and/or weight of ≥150 kg. This was a multicenter retrospective cohort study of severely obese adult patients with AF and/or VTE treated with a FXa inhibitor or warfarin. The primary effectiveness outcome was composite odds of stroke, systemic embolism, or VTE; the primary safety outcome was odds of major bleeding. Secondary outcomes included incidence of stroke or systemic embolism, VTE, major bleeding, clinically relevant nonmajor bleeding, all-cause mortality, change in anticoagulation, and total number of hospital encounters. Outcomes were assessed for 12 months following initiation of study drug. A total of 1736 patients were included. The mean weight and BMI of the overall cohort were 164.4 kg and 54.6 kg/m2, respectively. There was no difference in odds of stroke, systemic embolism or VTE (odds ratio, 1.005; 95% CI, 0.6-1.68), or major bleeding (odds ratio, 0.9; 95% CI, 0.47-1.7) between groups. These data suggest that apixaban and rivaroxaban are safe and effective alternatives to warfarin for the treatment of AF and/or VTE in individuals with a BMI of ≥50 kg/m2 and/or weight of ≥150 kg.

Dobry P ，Edwin SB ，Haymart B ，Barnes GD ，Kaatz S ，Ali MA ，Giuliano C ... -  《-》

Comparative effectiveness and safety of apixaban and rivaroxaban in older patients with atrial fibrillation: A population-based cohort study.

There are no clinical trials with a head-to-head comparison between the 2 most commonly used oral anticoagulants (apixaban and rivaroxaban) in patients with atrial fibrillation (AF). The comparative efficacy and safety between these drugs remain unclear, especially in older patients who are at the highest risk for stroke and bleeding. The purpose of this study was to compare the risk of major bleeding and thromboembolic events between apixaban and rivaroxaban in older patients with AF. We conducted a population-based retrospective cohort study of all adult patients (66 years or older) with AF in Ontario, Canada, who were treated with apixaban or rivaroxaban between April 1, 2011, and March 31, 2020. The primary safety outcome was major bleeding, and the primary efficacy outcome was thromboembolic events. Secondary outcomes included any bleeding. Rates and hazard ratios (HRs) were adjusted for baseline comorbidities with inverse probability of treatment weighting. This study included 42,617 patients with AF treated with apixaban and 30,725 patients treated with rivaroxaban. After inverse probability of treatment weighting using the propensity score, patients in the apixaban and rivaroxaban groups were well balanced for baseline values of demographic characteristics, comorbidities, and medications; both groups had a similar mean age of 77.4 years, and 49.9% were female. At 1 year, the apixaban group had a lower risk for both major bleeding with an absolute risk reduction at 1 year of 1.1% (2.1% vs 3.2%; HR 0.65; 95% confidence interval [CI] 0.59-0.71]) and any bleeding (8.1% vs 10.9%; HR 0.73; 95% CI 0.69-0.77), with no difference in the risk for thromboembolic events (2.2% vs 2.2%; HR 1.02; 95% CI 0.92-1.13). In patients with AF, 66 years or older, treatment with apixaban was associated with lower risk for major bleeding, with no difference in the risk for thromboembolic events compared with rivaroxaban.

Shurrab M ，Austin PC ，Jackevicius CA ，Tu K ，Qiu F ，Haldenby O ，Middleton A ，Turakhia MP ，Lopes RD ，Boden WE ，Castellucci LA ，Heidenreich PA ，Healey JS ，Ko DT ... -  《-》

Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin among Nursing Home Residents with Atrial Fibrillation: A Retrospective Cohort Study.

Residents of nursing homes are usually excluded from clinical trials, including trials to assess treatments for common conditions such as nonvalvular atrial fibrillation (NVAF). We aimed to quantify the real-world comparative safety and effectiveness of direct-acting oral anticoagulants (DOACs) vs warfarin among nursing home residents with NVAF. Retrospective cohort study using 100% national Minimum Data Set and linked Medicare claims from January 2011 through December 2018. Long-term care nursing home residents aged ≥66 years enrolled in fee-for-service Medicare. We included individuals diagnosed with NVAF newly initiating oral anticoagulants. We identified exposure to DOACs (apixaban, dabigatran, rivaroxaban, and edoxaban) vs warfarin. Outcomes were hospitalization for ischemic stroke/systemic embolism, major bleeding, pneumonia (negative control outcome), and all-cause death. We used inverse probability of treatment weighting competing risk regression models for clinical outcomes and Cox proportional hazards regression for all-cause death. Of 38,983 individuals newly initiating anticoagulants, 19,366 (49.7%) initiated DOACs and 19,617 (50.3%) initiated warfarin. In the inverse probability of treatment weighting analysis, compared with warfarin, there was no statistically significant association between DOAC use and ischemic stroke/systemic embolism [4.5 vs 4.7 events per 100 person-years; adjusted hazard ratio (aHR), 0.94; 95% CI, 0.84-1.05] or major bleeding (12.6 vs 12.4 events per 100 person-years; aHR, 1.03; 95% CI, 0.96-1.10). DOACs use was associated with a modest but statistically significant lower risk of all-cause death (48.1 vs 49.0 events per 100 person-years; IPTW analysis aHR, 0.95; 95% CI, 0.91-0.98). Among nursing home residents with NVAF, DOACs and warfarin were associated with a similar risk of ischemic stroke/systemic embolism and major bleeding. However, the use of DOACs was associated with a slightly reduced risk of all-cause mortality.

Mehta HB ，Xiao X ，An H ，Alexander GC ... -  《-》

Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial.

McIntyre WF ，Benz AP ，Healey JS ，Connolly SJ ，Yang M ，Lee SF ，Field TS ，Alings M ，Benezet-Mazuecos J ，Boriani G ，Nielsen JC ，Gold MR ，Pergolini F ，Glotzer TV ，Granger CB ，Lopes RD ... -  《-》

Standard- versus extended-duration anticoagulation for primary venous thromboembolism prophylaxis in acutely ill medical patients.

Venous thromboembolism (VTE) includes two interrelated conditions, deep vein thrombosis (DVT) and pulmonary embolism (PE). Risk factors include dehydration, prolonged immobilization, acute medical illness, trauma, clotting disorders, previous thrombosis, varicose veins with superficial vein thrombosis, exogenous hormones, malignancy, chemotherapy, infection, inflammation, pregnancy, obesity, smoking, and advancing age. It is estimated that hospitalized patients are 100 times more likely to develop VTE and, compared with surgical patients, medical patients often have more severe forms of VTE. VTE carries a significant risk of morbidity and mortality. Prophylactic strategies, including mechanical and pharmacological methods, are recommended for patients at risk of VTE. Pharmacological prophylaxis is considered the standard practice for acutely ill medical patients at risk of developing VTE in the absence of contraindications. For hospitalized patients, the risk of VTE extends beyond hospital stay and up to 90 days, with most events occurring within 45 days of discharge. Despite that, it remains unclear whether extended-duration anticoagulation for primary VTE prophylaxis would provide benefits without added risks or harm. To assess the benefits and risks of standard- versus extended-duration anticoagulation for primary VTE prophylaxis in acutely ill medical patients. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialized Register, CENTRAL, MEDLINE, Embase, CINAHL and Web of Science databases, as well as the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers up to 27 March 2023. We also searched reference lists of all included studies for additional references and searched the last five years of the American Society of Hematology conference proceedings. We included randomized controlled trials (RCTs) comparing standard-duration versus extended-duration anticoagulation for primary VTE prophylaxis in acutely ill medical patients (adults being treated in a medical inpatient setting). We used the standard methodological procedures set by Cochrane. At least two authors independently screened titles and abstracts for inclusion and performed data extraction. Two authors independently assessed the risk of bias (RoB) using the Cochrane RoB 2 tool. We analyzed outcomes data using the risk ratio (RR) with 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence for each outcome. Our outcomes of interest were assessed in the short term (during the treatment period and within 45 days of hospitalization) and long term (assessed beyond 45 days of hospitalization). Primary outcomes were symptomatic VTE, major bleeding, and all-cause mortality. Secondary outcomes were total VTE, a composite of fatal and irreversible vascular events (including myocardial infarction, non-fatal PE, cardiopulmonary death, stroke), fatal bleeding, and VTE-related mortality. A total of seven RCTs fulfilled our inclusion criteria, comprising 40,846 participants. All studies contributing data to our outcomes were at low risk of bias in all domains. Most studies reported the outcomes in the short term. Extended-duration anticoagulation, compared with standard-duration anticoagulation, for primary VTE prophylaxis in acutely ill medical patients reduced the risk of short-term symptomatic VTE (RR 0.60, 95% CI 0.46 to 0.78; standard-duration 12 per 1000, extended-duration 7 per 1000, 95% CI 6 to 10; number needed to treat for an additional beneficial outcome [NNTB] 204, 95% CI 136 to 409; 4 studies, 24,773 participants; high-certainty evidence). This benefit, however, was offset by an increased risk of short-term major bleeding (RR 2.05, 95% CI 1.51 to 2.79; standard-duration 3 per 1000, extended duration 6 per 1000, 95% CI 5 to 8; number needed to treat for an additional harmful outcome [NNTH] 314, 95% CI 538 to 222; 7 studies, 40,374 participants; high-certainty evidence). Extended-duration anticoagulation, compared with standard-duration, results in little to no difference in short-term all-cause mortality (RR 0.97, 95% CI 0.87 to 1.08; standard-duration 34 per 1000, extended-duration 33 per 1000, 95% CI 30 to 37; 5 studies, 38,080 participants; high-certainty evidence), reduced short-term total VTE (RR 0.75, 95% CI 0.67 to 0.85; standard-duration 37 per 1000, extended duration 28 per 1000, 95% CI 25 to 32; NNTB 107, 95% CI 76 to 178; 5 studies, 33,819 participants; high-certainty evidence), and short-term composite of fatal and irreversible vascular events (RR 0.71, 95% CI 0.56 to 0.91; standard-duration 41 per 1000, extended-duration 29 per 1000, 95% CI 23 to 37; NNTB 85, 95% CI 50 to 288; 1 study, 7513 participants; high-certainty evidence). Extended-duration anticoagulation may result in little to no difference in short-term fatal bleeding (RR 2.28, 95% CI 0.84 to 6.22; standard-duration 0 per 1000, extended-duration 0 per 1000, 95% CI 0 to 1; 7 studies, 40,374 participants; low-certainty evidence), and likely results in little to no difference in short-term VTE-related mortality (RR 0.78, 95% CI 0.58 to 1.05; standard-duration 5 per 1000, extended-duration 4 per 1000 95% CI 3 to 6; 6 studies, 36,170 participants; moderate-certainty evidence). In the short term, extended- versus standard-duration anticoagulation for primary VTE prophylaxis in acutely ill medical patients reduced the risk of symptomatic VTE at the expense of an increased risk of major bleeding. Extended-duration anticoagulation resulted in little to no difference in all-cause mortality. Extended-duration anticoagulation reduced the risk of total VTE and the composite of fatal and irreversible vascular events, but may show little to no difference in fatal bleeding and VTE-related mortality. Further data, with longer follow-up, are needed to determine the optimal agent and duration for primary VTE prophylaxis in acutely ill medical patients.

Kolkailah AA ，Abdelghaffar B ，Elshafeey F ，Magdy R ，Kamel M ，Abuelnaga Y ，Nabhan AF ，Piazza G ... -  《Cochrane Database of Systematic Reviews》