Effectiveness and safety of apixaban and rivaroxaban for acute venous thromboembolism therapy in patients with extremes in bodyweight.

OBJECTIVES: To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with bodyweight <60 kg, 60-120 kg, and >120 kg. METHODS: Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview. RESULTS: Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight < 60 kg, and 230 (8.9%) had bodyweight >120 kg. Patients with bodyweight <60 kg treated with DOACs had higher 3- and 6-month incidence of major bleeding compared to the bodyweight 60-120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight >120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (P = .01). CONCLUSIONS: Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight >120 kg on rivaroxaban.

DOACs Versus VKAs in Older Adults Treated for Acute Venous Thromboembolism: Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTVES: Four direct-acting oral anticoagulants (DOACs) are currently approved by the Food and Drug Administration for the treatment of venous thromboembolism (VTE). Limited efficacy and safety data are available for their use in older adults (aged ≥75 years). METHODS: Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for trials comparing DOACs with vitamin K antagonists (VKAs) for the treatment of VTE in older adults from inception through January 1, 2020. Meta-analysis was performed to assess the combined endpoint of recurrent VTE and related deaths and bleeding events (composite of major and clinically relevant nonmajor bleeding). The Mantel-Haenszel relative risk (RR) random effects model was used to pool results across studies. RESULTS: Six randomized controlled trials at low risk of bias met criteria for inclusion with a total of 3,665 patients aged 75 years and older with follow-up of 24 weeks or longer. Data for bleeding events were not available for dabigatran. Overall, DOACs had an improved efficacy over VKAs (RR = .56; 95% confidence interval [CI] = .38-.82). There was no statistically significant difference in the safety outcomes (RR = .77; 95% CI = .56-1.05). No significant heterogeneity was observed for efficacy outcome, and only moderate heterogeneity was observed for safety outcome. CONCLUSION: In older adults with VTE, DOACs appear to improve rates of recurrent VTE and VTE-related deaths compared with VKAs with similar bleeding outcomes.

Treatment of upper extremity deep vein thrombosis with apixaban and rivaroxaban.

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.

Resolution of acute lower extremity deep vein thrombosis with rivaroxaban compared to warfarin.

Thrombosis resolution is an important component of treatment for deep vein thrombosis (DVT) and multiple anticoagulants are now available. It is unknown whether rivaroxaban contributes to a higher degree of thrombus resolution compared to conventional anticoagulation with warfarin. Our objective was to compare thrombus resolution for rivaroxaban versus warfarin treated patients with acute lower extremity DVT. Consecutive patients treated for proximal or distal lower extremity DVT with rivaroxaban were identified from the Mayo Thrombophilia Clinic Anticoagulants Registry (November 2015-June 2016) and compared to patients treated with warfarin. Ultrasonography/Doppler images were analyzed by two independent radiologists blinded to anticoagulant and using a standardized assessment algorithm. A total of 111 patients with DVT were studied. Sixty-three rivaroxaban treated patients were compared to 48 warfarin treated patients over a median follow up of 92 and 97 days, respectively. Percentage of patients with total or partial resolution of thrombosis was similar in rivaroxaban and warfarin treated groups (95.2% vs. 91.7%, p = 0.46, respectively); also the proportion of patients with total thrombus resolution was not significantly different (38.1% vs. 29.2%, p = 0.42, respectively). There was no significant difference in the proportion of patients with no thrombus resolution between rivaroxaban and warfarin treated groups either (4.8% vs. 2.1%, p = 0.63). Thrombus propagation with warfarin therapy was observed in 6.3% of patients treated with warfarin and in none of the patients from the rivaroxaban group (p = 0.08). Resolution of acute lower extremity DVT in patients treated with rivaroxaban is similar to those treated with warfarin.

Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer-associated venous thromboembolism.

To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer-associated venous thromboembolism (Ca-VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non-major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca-VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51-3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban (P = .03) and LMWH (P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.

Apixaban and Rivaroxaban in Patients With Acute Venous Thromboembolism.

OBJECTIVE: To compare the clinical efficacy and safety of apixaban with those of rivaroxaban for the treatment of acute venous thromboembolism (VTE). PATIENTS AND METHODS: Consecutive patients enrolled in the Mayo Thrombophilia Clinic Registry (between March 1, 2013, and January 30, 2018) and treated with apixaban or rivaroxaban for acute VTE were followed forward in time. The primary efficacy outcome was VTE recurrence. The primary safety outcome was major bleeding; the second safety outcome was clinically relevant nonmajor bleeding (CRNMB); and the third was a composite of major bleeding or CRNMB. RESULTS: Within the group of 1696 patients with VTE enrolled, 600 (38%) were treated either with apixaban (n=302, 50%) or rivaroxaban (n=298, 50%) within the first 14 days of VTE diagnosis and who completed at least 3 months of therapy or had a study event. Recurrent VTE was diagnosed in 7 patients (2.3%) treated with apixaban and in 6 (2%) treated with rivaroxaban (adjusted hazard ratio [aHR], 1.4; 95% CI, 0.5-3.8). Major bleeding occurred in 11 patients (3.6%) receiving apixaban and in 9 patients (3.0%) receiving rivaroxaban (aHR, 1.2; 95% CI, 0.5-3.2). Clinically relevant nonmajor bleeding was diagnosed in 7 patients (2.3%) receiving apixaban and in 20 (6.7%) receiving rivaroxaban (aHR, 0.4; 95% CI, 0.2-0.9). The rates of composite major bleeding or CRNMB were similar (aHR, 0.6; 95% CI, 0.3-1.2). Most study events occurred in patients with cancer. CONCLUSION: In the setting of a standardized, guideline-directed, patient-oriented clinical practice, the efficacy and safety of apixaban and rivaroxaban for the treatment of acute VTE were comparable.

Rivaroxaban and Apixaban for Initial Treatment of Acute Venous Thromboembolism of Atypical Location.

OBJECTIVES: To assess the outcome of direct oral anticoagulants (DOACs), specifically Xa inhibitors: rivaroxaban and apixaban, for the treatment of venous thromboembolism (VTE) of atypical location (VTE-AL), portal, mesenteric, hepatic, splenic, gonadal, renal, and cerebral veins, prospectively collected data of Mayo Thrombophilia Clinic Registry were used. METHODS: Patients with acute VTE-AL treated with DOACs, enrolled between March 1, 2013, and February 1, 2017, were compared with patients with VTE of typical location (VTE-TL: deep vein thrombosis of extremities and/or pulmonary embolism) receiving DOACs and with patients with VTE-AL treated with enoxaparin. RESULTS: Out of 623 patients with acute VTE receiving the study drug within 14 days of diagnosis, there were 63 with VTE-AL: 36 on DOAC, 23 on enoxaparin, and 4 on warfarin; 352 received DOAC for VTE-TL. The VTE-AL treated with DOAC/enoxaparin included the following: splanchnic (26/22), ovarian (8/2), renal (3/5), and cerebral veins (1/1), respectively. Recurrence rate (per 100 person-years) for the VTE-AL group receiving DOAC was 7.3, which was not different when compared with those for VTE-TL (2.4; P=.13) and VTE-AL groups receiving enoxaparin (23.7; P=.37). Major bleeding rate in the VTE-AL group receiving DOAC was not different compared with those for VTE-TL (7.2 vs 3.0; P=.26) and VTE-AL groups on enoxaparin (22.4; P=.31). Mortality was higher in the VTE-AL group on DOAC compared with the VTE-TL group (21.45 [95% CI, 7.87-46.69] vs 8.26 [95% CI, 5.35, 12.20]; P=.03). All patients with VTE-AL with events had cancer. CONCLUSION: The VTE recurrence and bleeding rates for rivaroxaban and apixaban used in VTE-AL are not different from those in patients with VTE-TL and similar to that for enoxaparin.

Efficacy and Safety of Rivaroxaban in Patients with Venous Thromboembolism and Active Malignancy: A Single-Center Registry.

OBJECTIVE: The purpose of this study is to evaluate the efficacy and safety of rivaroxaban in patients with venous thromboembolism and active malignancy, given the paucity of clinical data with the use of direct Xa inhibitors in this high-risk population. PATIENTS AND METHODS: Consecutive patients treated with rivaroxaban for deep vein thrombosis or pulmonary embolism, enrolled into Mayo Thrombophilia Clinic Direct Oral Anticoagulants Registry between March 1, 2013, and April 30, 2015, were followed prospectively to evaluate the efficacy and safety of this therapy. RESULTS: Of the 404 venous thromboembolism patients in the registry, 296 received rivaroxaban and had at least 3 months of follow-up. Of these, 118 (40%) had active malignancy (51% female, mean age 66 ± 10 years) and 178 had no cancer (47% female, mean age 55 ± 15 years). The 3 most common cancer locations were genitourinary (23.6%), gastrointestinal (20.3%), and lung (13.5%). There was no difference in venous thromboembolism recurrence between the malignant (3.3%) and the nonmalignant (2.8%) venous thromboembolism groups (P = .533). Borderline higher rates for major bleeding (P = .06) and nonmajor clinically relevant bleeding (P = .08) were observed in patients with cancer. CONCLUSIONS: The "real world" effectiveness and safety of rivaroxaban is similar for venous thromboembolism patients with and without active malignancy.

Failure of dabigatran and rivaroxaban to prevent thromboembolism in antiphospholipid syndrome: a case series of three patients.

Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.

Periprocedural anticoagulant management.

Approximately 6 million Americans are treated with chronic anticoagulation. Of these, 10% of patients will require temporary anticoagulation interruption for an invasive procedure each year. Anticoagulation management during this period requires a formal strategy in order to limit both bleeding and thromboembolic complications. This article will give health care providers a stepwise approach to this process. The first step is to determine whether warfarin discontinuation is necessary for the planned procedure. For procedures requiring warfarin discontinuation, the second step is to determine the appropriate timing. The third step is to identify the patient-specific thromboembolic risk in order to determine which patients require bridging therapy with parenteral anticoagulants. The fourth step is both the most complicated and most critical step in this management strategy. This decision-making step involves choosing the appropriate anticoagulant regimen, dose, and timing of reinitiation that is best tailored to a specific patient, as well as determining procedural variables, in order to limit bleeding and thrombotic complications.