Association of Type of Oral Anticoagulant Dispensed With Adverse Clinical Outcomes in Patients Extending Anticoagulation Therapy Beyond 90 Days After Hospitalization for Venous Thromboembolism.

Importance: Guidelines for managing venous thromboembolism (VTE) recommend at least 90 days of therapy with oral anticoagulants. Limited evidence exists about the optimal drug for continuing therapy beyond 90 days. Objective: To compare having prescriptions dispensed for apixaban, rivaroxaban, or warfarin after an initial 90 days of anticoagulation therapy for the outcomes of hospitalization for recurrent VTE, major bleeding, and death. Design, Setting, and Participants: This exploratory retrospective cohort study used data from fee-for-service Medicare (2009-2017) and from 2 commercial health insurance (2004-2018) databases and included 64 642 adults who initiated oral anticoagulation following hospitalization discharge for VTE and continued treatment beyond 90 days. Exposures: Apixaban, rivaroxaban, or warfarin prescribed after an initial 90-day treatment for VTE. Main Outcomes and Measures: Primary outcomes included hospitalization for recurrent VTE and hospitalization for major bleeding. Analyses were adjusted using propensity score weighting. Patients were followed up from the end of the initial 90-day treatment episode until treatment cessation, outcome, death, disenrollment, or end of available data. Weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. Results: The study included 9167 patients prescribed apixaban (mean [SD] age, 71 [14] years; 5491 [59.9%] women), 12 468 patients prescribed rivaroxaban (mean [SD] age, 69 [14] years; 7067 [56.7%] women), and 43 007 patients prescribed warfarin (mean [SD] age, 70 [15] years; 25 404 [59.1%] women). The median (IQR) follow-up was 109 (59-228) days for recurrent VTE and 108 (58-226) days for major bleeding outcome. After propensity score weighting, the incidence rate of hospitalization for recurrent VTE was significantly lower for apixaban compared with warfarin (9.8 vs 13.5 per 1000 person-years; HR, 0.69 [95% CI, 0.49-0.99]), but the incidence rates were not significantly different between apixaban and rivaroxaban (9.8 vs 11.6 per 1000 person-years; HR, 0.80 [95% CI, 0.53-1.19]) or rivaroxaban and warfarin (HR, 0.87 [95% CI, 0.65-1.16]). Rates of hospitalization for major bleeding were 44.4 per 1000 person-years for apixaban, 50.0 per 1000 person-years for rivaroxaban, and 47.1 per 1000 person-years for warfarin, yielding HRs of 0.92 (95% CI, 0.78-1.09) for apixaban vs warfarin, 0.86 (95% CI, 0.71-1.04) for apixaban vs rivaroxaban, and 1.07 (95% CI, 0.93-1.24) for rivaroxaban vs warfarin. Conclusions and Relevance: In this exploratory analysis of patients prescribed extended-duration oral anticoagulation therapy after hospitalization for VTE, prescription dispenses for apixaban beyond 90 days, compared with warfarin beyond 90 days, were significantly associated with a modestly lower rate of hospitalization for recurrent VTE, but no significant difference in rate of hospitalization for major bleeding. There were no significant differences for comparisons of apixaban vs rivaroxaban or rivaroxaban vs warfarin.

Safety and Efficacy Evaluation of Antithrombotic Therapy with Rivaroxaban and Clopidogrel After PCI in Chinese Patients.

OBJECTIVE: To investigate the efficacy and safety of the antithrombotic therapy using the oral anticoagulant rivaroxaban and clopidogrel in Chinese patients with acute coronary syndrome complicated with atrial fibrillation after percutaneous coronary intervention. METHODS: A total of 100 patients were selected. Patients were randomly divided into two groups: the treatment group (rivaroxaban group) received a therapy of rivaroxaban and clopidogrel. The control group (warfarin group) receivied a combined treatment of warfarin, clopidogrel, and aspirin. The primary outcome endpoint was evaluated based on the adverse cardiac and cerebrovascular events within 12 months. RESULTS: A total of 8 (8.00%) main adverse cardiac and cerebrovascular events occurred during the 12 months of follow-up, including 5 (9.80%) in the warfarin group and 3 (6.10%) in the rivaroxaban group. The risk of having main adverse cardiac and cerebrovascular events in the two groups was comparable (P = 0.479). A total of 9 patients (9.00%) were found to have bleeding events, among which 8 patients (15.7%) were in the warfarin group, whereas only 1 patient (2.00%) was in the rivaroxaban group. Therefore, the risk of bleeding in the warfarin group was significantly higher than that in the rivaroxaban group (P = 0.047). CONCLUSIONS: In Chinese patients with acute coronary syndrome complicated with atrial fibrillation, the efficacy of the dual therapy of oral anticoagulant rivaroxaban plus clopidogrel after percutaneous coronary intervention was similar to that of the traditional triple therapy combined with warfarin, aspirin and clopidogrel, but it has a better safety property, which has potential to widely apply to antithrombotic therapy after PCI.

Effect of Rivaroxaban and Clopidogrel Combination Therapy on In-Stent Responses After Everolimus-Eluting Stent Implantation in a Porcine Coronary Model.

AIM: According to recent clinical trials, a combination of direct oral anticoagulants with antiplatelet drugs is often recommended for atrial fibrillation patients who receive drug-eluting stents (DESs). Although the optimal combination comprises direct factor Xa inhibitors and a P2Y12 receptor antagonist (or aspirin), their influence on vascular responses to DESs remains unclear. METHODS: Pigs were given either aspirin and clopidogrel (dual antiplatelet therapy [DAPT] group), aspirin and rivaroxaban (AR group), or clopidogrel and rivaroxaban (CR group), followed by everolimus-eluting stent (Promus Element) implantation into the coronary artery. Stented coronary arteries were evaluated via intravascular optical coherence tomography (OCT) and histological analysis at 1 and 3 months. RESULTS: OCT revealed lower neointimal thickness in the DAPT group and comparable thickness among all groups at 1 and 3 months, respectively. Histological analyses revealed comparable neointimal area among all groups and the smallest neointimal area in the CR group at 1 and 3 months, respectively. In the DAPT and AR groups, the neointima continued to grow from 1 to 3 months. A shortened time course for neointima growth was observed in the CR group, with rapid growth within a month (maintained for 3 months). A higher incidence of in-stent thrombi was observed in the AR group at 1 month; no thrombi were found in either group at 3 months. More smooth muscle cells with contractile features were found in the CR group at both 1 and 3 months. CONCLUSIONS: Our results proved the noninferiority of the combination of rivaroxaban with an antiplatelet drug, particularly the dual therapy using rivaroxaban and clopidogrel, compared to DAPT after DES implantation.

Exploratory Evaluation of Rhythm Control by Dronedarone in Combination With Low-Dose Rivaroxaban, Warfarin, Antiplatelet, or None of the Antithrombotic Therapy in High-Risk Patients With Non-Permanent Atrial Fibrillation: A Retrospective Cohort Study.

The emerging data supports rhythm control to prevent major adverse cardiac events (MACE) in high-risk patients with atrial fibrillation (AF). Limited data demonstrated rivaroxaban 10 mg combining dronedarone seemed feasible. This study aimed at investigating clinical events in a dronedarone-treated cohort. This exploratory, retrospective chart review was conducted in nonpermanent AF patients receiving dronedarone for ≥ 3 months between 2009/1 and 2016/2. In Taiwan, dronedarone's labeled indication was strict to age ≥ 70 or 65 to 70 years with either hypertension, diabetes, prior stroke, or left atrium >50 mm. We divided all into 4 groups using antithrombotic strategies to evaluate the safety, effectiveness, and MACE endpoints. A total of 689 patients (mean CHA2DS2-VASc score 3.8 ± 1.4) were analyzed: rivaroxaban 10 mg (n = 93, 13.5%), warfarin (n = 89, 12.9%), antiplatelet (n = 331, 48.0%), and none (n = 176, 25.5%). During the follow-up period (mean 946 ± 493.8 days), the rivaroxaban group did not report any stroke or thromboembolism (ishcmeic stroke rate: antiplatelet [0.6%], none [1.1%]; hemorrahgic stroke rate: warfarin [2.2%]; thromboembolism rate: warfarin [2.2%]). There was no significant difference in safety, effectiveness, and MACE endpoints between groups. Also, >104 weeks of dronedarone use was the independent predictor for MACE after adjusting the strategy and other covariates (hazard ratio 0.14 [95% confidence interval 0.04-0.44], P = .001). Our findings warrant concomitant rivaroxaban 10 mg and dronedarone for further investigation. Regardless of antithrombotic strategies, a more extended persistence of dronedarone was associated with fewer MACE.

Cancer-associated thrombosis - treatment and prevention with direct oral factor Xa inhibitors.

BACKGROUND: Venous thromboembolism (VTE) is a frequent cause of morbidity and mortality in patients with cancer. Moreover, management of VTE is frequently connected with complications, namely risk of recurrent VTE and bleeding. Low molecular weight heparins (LMWH) therapy administrated for 3-6 months is currently considered a standard for the treatment of cancer-associated VTE (CA-VTE). Direct oral factor Xa inhibitors (FXaI) apixaban, edoxaban and rivaroxaban have emerged as a new possibility for long-term antithrombotic therapy for VTE. These agents expose several advantages in individuals with cancer, and might overcome several disadvantages connected with LMWH therapy. PURPOSE: First clinical studies with oral FXaI for the treatment of CA-VTE with very promising results were recently published. The article summarizes current data regarding the use of oral FXaI in the treatment of CA-VTE.

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial.

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.

The efficacy and safety of rivaroxaban in coronary artery disease patients with heart failure and sinus rhythm: a systematic review and meta-analysis.

PURPOSE: To explore the efficacy and safety of rivaroxaban in patients with coronary artery disease (CAD), heart failure (HF) and sinus rhythm (SR). METHODS: Comprehensive literature searches were conducted using the PubMed, Cochrane Library, Embase, CNKI and Wanfang databases from inception to February 2021. Randomized controlled trials (RCTs) focusing on the efficacy and safety of new oral anticoagulant (NOAC) therapy in CAD and HF patients in SR were eligible. Statistical analyses were performed using R Programming Language. RESULTS: Three RCTs included 10,658 adult patients treated with antiplatelet drugs with or without rivaroxaban were ultimately analysed. The average follow-up period was 20.4-24 months. Rivaroxaban had a favourable point estimate in myocardial infarction (MI) and stroke (MI rivaroxaban group (3.83%, 203/5306) vs. APT group (4.52%, 214/4731), RR = 0.78, 95% CI 0.65-0.94, P < 0.01, I2 = 0%), (stroke: rivaroxaban group (1.60%, 85/5306) vs. APT group (2.52%, 119/4731), RR = 0.64, 95% CI 0.49-0.85, P < 0.01, I2 = 12%) compared with the placebo. Rivaroxaban was comparable to the placebo for all-cause death and major bleeding (all-cause death: rivaroxaban group (12.27%, 688/5606) vs. APT group (14.59%, 737/5052), RR = 0.73, 95% CI 0.49-1.06, P > 0.05, I2 = 87%), (major bleeding: rivaroxaban group (1.52%, 85/5586) vs. APT group (1.37%, 69/5043), RR = 1.18, 95% CI 0.86-1.62, P > 0.05, I2 = 0%). CONCLUSIONS: In SR patients with CAD and HF, the rates of MI and stroke associated with rivaroxaban combined with APT were lower than those associated with APT alone, and the two treatments had similar rates of all-cause death and major bleeding.

An emulated target trial analysis based on Medicare data suggested non-inferiority of Dabigatran versus Rivaroxaban.

OBJECTIVES: Rivaroxaban and Dabigatran were the first two non-vitamin K antagonist oral anticoagulants (NOACs) for preventing stroke among non-valvular Atrial Fibrillation patients. This article aimed to evaluate the relative efficacy and safety of Rivaroxaban versus Dabigatran. STUDY DESIGN AND SETTING: An emulated target trial analysis was conducted based on Medicare, in which we constructed three "randomized clinical trials" with well-defined inclusion/exclusion criteria, treatment regimens, and analysis procedures. We analyzed the individual trials, examined temporal variations, and generated unified results via pooled analysis. RESULTS: With a two-year data collection window (2012-2013), 70,129 subjects were enrolled in the three emulated trials, with 36,269 and 34,089 in the Rivaroxaban and Dabigatran arms, respectively. Dabigatran (the reference group for hazard ratio - HR) was superior regarding time to any primary event (including ischemic stroke, other thromboembolic events, major bleeding, and death; HR 1.232, P-value 0.0025), major bleeding (HR 1.187, P-value <0.0001), and mortality (HR 1.488, P-value <0.0001). Differences regarding stroke and other thromboembolic events were not significant. CONCLUSION: Dabigatran was found as superior for the Medicare patients with multiple chronic conditions. Temporal variations, which had been largely neglected in the literature, were observed. This study may provide new insight into treating AF with NOACs.

Comparison of Low-Dose Direct Acting Anticoagulant and Warfarin in patients Aged ≥80 years With Atrial Fibrillation.

Low dose direct acting oral anticoagulants (LDDOACS) were approved for elderly atrial Fibrillation (AF) patients with limited information. A retrospective analysis collecting baseline characteristics and outcomes in AF patients ≥ 80 prescribed LDDOAC or warfarin (W), from a multidisciplinary practice between 1/1/11 (First LDDOAC available) and 5/31/17 was conducted. From 9660 AF patients, 514 ≥ 80 received a LDDOAC and 422 W. A multivariable comparison found LDDOAC patients were older (p <0.001), had lower creatinine clearance (CrCl) (p = 0.006), used more anti-platelet drugs (p <0.001), and more often had new onset AF verses those prescribed W (p <0.001). There were no clinically significant differences among those patients receiving Dabigatran 75 mgs BID (D), Rivaroxaban 15mgs (R) or Apixaban 2.5mgs BID (A). Forty-eight and 50% of the patients remained on their LDDOAC or W for the observation period (p = 0.55). Stroke/systemic embolism (SSE) and CNS bleeds were 1.16 vs 2.22%/yr., (p = 0.143) and 1.46 vs 0.93%/yr., (p = 0.24). Mortality and major bleeds were 6.26 vs 1.67%/yr., and 12.3vs 3.77%/yr. (p <0.001). SSE were 1.1%/yr for D, R, and A (p = 0.94). CNS bleeds were 2.2 for D, 1.7 for R and 0.8%/yr. for A: p = 0.53. Major bleeding was: 14.3 for D, 14.1 for R and 9.1%/yr. for A, p = 0.048 (with A < R, p = 0.01). Mortality was 5.5 for D, 4.2 for R and 9.5% for A, p = 0.031. In conclusion, half the patients remained on their assigned anti-coagulant. SSE and intracranial bleed rates were similar and low. Major bleeds and deaths were different between groups emphasizing the need for prospective randomized trials in this growing population with AF.

Appropriate intraprocedural initial heparin dosing in patients undergoing catheter ablation for atrial fibrillation receiving uninterrupted non-vitamin-K antagonist oral anticoagulant treatment.

BACKGROUND: To clarify the appropriate initial dosage of heparin during radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) receiving uninterrupted nonvitamin K antagonist oral anticoagulant (NOAC) treatment. METHODS: A total of 187 consecutive AF patients who underwent their first RFCA in our center were included. In the warfarin group (WG), an initial heparin dose of 100 U/kg was administered (control group: n = 38). The patients who were on NOACs were randomly divided into 3 NOAC groups (NG: n = 149), NG110, NG120, and NG130, and were administered initial heparin doses of 110 U/kg, 120 U/kg, and 130 U/kg, respectively. During RFCA, the activated clotting time (ACT) was measured every 15 min, and the target ACT was maintained at 250-350 s by intermittent heparin infusion. The baseline ACT and ACTs at each 15-min interval, the average percentage of measurements at the target ACT, and the incidence of periprocedural bleeding and thromboembolic complications were recorded and analyzed. RESULTS: There was no significant difference in sex, age, weight, or baseline ACT among the four groups. The 15 min-ACT, 30 min-ACT, and 45 min-ACT were significantly longer in the WG than in NG110 and NG120. However, no significant difference in 60 min-ACT or 75 min-ACT was detected. The average percentages of measurements at the target ACT in NG120 (82.2 ± 23.6%) and NG130 (84.8 ± 23.7%) were remarkably higher than those in the WG (63.4 ± 36.2%, p = 0.007, 0.003, respectively). These differences were independent of the type of NOAC. The proportion of ACTs in 300-350 s in NG130 was higher than in WG (32.4 ± 31.8 vs. 34.7 ± 30.6, p = 0.735). Severe periprocedural thromboembolic and bleeding complications were not observed. CONCLUSIONS: For patients with AF receiving uninterrupted NOAC treatment who underwent RFCA, an initial heparin dosage of 120 U/kg or 130 U/kg can provide an adequate intraprocedural anticoagulant effect, and 130 U/kg allowed ACT to reach the target earlier. TRIAL REGISTRATION: Registration number: ChiCTR1800016491, First Registration Date: 04/06/2018 (Chinese Clinical Trial Registry http://www.chictr.org.cn/index.aspx ).

Randomized clinical trial to evaluate a routine full anticoagulation Strategy in Patients with Coronavirus Infection (SARS-CoV2) admitted to hospital: Rationale and design of the ACTION (AntiCoagulaTlon cOroNavirus)-Coalition IV trial.

BACKGROUND: Observational studies have suggested a higher risk of thrombotic events in patients with coronavirus disease 2019 (COVID-19). Moreover, elevated D-dimer levels have been identified as an important prognostic marker in COVID-19 directly associated with disease severity and progression. Prophylactic anticoagulation for hospitalized COVID-19 patients might not be enough to prevent thrombotic events; therefore, therapeutic anticoagulation regimens deserve clinical investigation. DESIGN: ACTION is an academic-led, pragmatic, multicenter, open-label, randomized, phase IV clinical trial that aims to enroll around 600 patients at 40 sites participating in the Coalition COVID-19 Brazil initiative. Eligible patients with a confirmed diagnosis of COVID-19 with symptoms up to 14 days and elevated D-dimer levels will be randomized to a strategy of full-dose anticoagulation for 30 days with rivaroxaban 20 mg once daily (or full-dose heparin if oral administration is not feasible) vs standard of care with any approved venous thromboembolism prophylaxis regimen during hospitalization. A confirmation of COVID-19 was mandatory for study entry, based on specific tests used in clinical practice (RT-PCR, antigen test, IgM test) collected before randomization, regardless of in the outpatient setting or not. Randomization will be stratified by clinical stability at presentation. The primary outcome is a hierarchical analysis of mortality, length of hospital stay, or duration of oxygen therapy at the end of 30 days. Secondary outcomes include the World Health Organization's 8-point ordinal scale at 30 days and the following efficacy outcomes: incidence of venous thromboembolism , acute myocardial infarction, stroke, systemic embolism, major adverse limb events, duration of oxygen therapy, disease progression, and biomarkers. The primary safety outcomes are major or clinically relevant non-major bleeding according to the International Society on Thrombosis and Haemostasis criteria. SUMMARY: The ACTION trial will evaluate whether in-hospital therapeutic anticoagulation with rivaroxaban for stable patients, or enoxaparin for unstable patients, followed by rivaroxaban through 30 days compared with standard prophylactic anticoagulation improves clinical outcomes in hospitalized patients with COVID-19 and elevated D-dimer levels.

Treatment with direct oral anticoagulants or warfarin and the risk for incident diabetes among patients with atrial fibrillation: a population-based cohort study.

BACKGROUND: Diabetes mellitus is a common comorbidity of atrial fibrillation (AF), which can complicate the management of AF. The pharmacology of oral anticoagulants (OACs) have been implicated in pathogenesis of diabetes, but the relationship between different OACs and risk of diabetes remains unexamined. This study aimed to evaluate the risk of diabetes with use of different OACs in AF patients. METHODS: Population-based retrospective cohort study using an electronic healthcare database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with AF from 2014 through 2018 and prescribed OACs were included and followed till December 31, 2019. Inverse probability of treatment weighting based on the propensity score (PS) is used to address potential bias due to nonrandomized allocation of treatment. The risks ofdiabetes were compared between different new OAC users using propensity score-weighted cumulative incidence differences (CID). RESULTS: There were 13,688 new users of OACs (warfarin: n = 3454; apixaban: n = 3335; dabigatran: n = 4210; rivaroxaban: n = 2689). The mean age was 75.0 (SD, 11.2), and 6,550 (47.9%) were women. After a median follow-up of 0.93 years (interquartile range, 0.21-1.92 years), 698 incident diabetes cases were observed. In Cox-regression analysis, dabigatran use was significantly associated with reduced risk of diabetes when compared with warfarin use [HR 0.69 (95% CI 0.56-0.86; P < 0.001)], with statistically insignificant associations observed for use of apixaban and rivaroxaban. The corresponding adjusted CIDs at 2 years after treatment with apixaban, dabigatran, and rivaroxaban users when compared with warfarin were - 2.06% (95% CI - 4.08 to 0.16%); - 3.06% (95% CI - 4.79 to - 1.15%); and - 1.8% (- 3.62 to 0.23%). In head-to-head comparisons between women DOAC users, dabigatran was also associated with a lower risk of diabetes when compared with apixaban and rivaroxaban. CONCLUSIONS: Among adults with AF receiving OACs, the use of dabigatran had the lowest risk of diabetes when compared with warfarin use.

Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: A Multicenter Randomized Controlled Trial.

BACKGROUND: In patients with normal renal function or early stage CKD, the risk-benefit profile of direct oral anticoagulants (DOACs) is superior to that of vitamin K antagonists (VKAs). In patients on hemodialysis, the comparative efficacy and safety of DOACs versus VKAs are unknown. METHODS: In the Valkyrie study, 132 patients on hemodialysis with atrial fibrillation were randomized to a VKA with a target INR of 2-3, 10 mg rivaroxaban daily, or rivaroxaban and vitamin K2 for 18 months. Patients continued the originally assigned treatment and follow-up was extended for at least an additional 18 months. The primary efficacy end point was a composite of fatal and nonfatal cardiovascular events. Secondary efficacy end points were individual components of the composite outcome and all-cause death. Safety end points were life-threatening, major, and minor bleeding. RESULTS: Median (IQR) follow-up was 1.88 (1.01-3.38) years. Premature, permanent discontinuation of anticoagulation occurred in 25% of patients. The primary end point occurred at a rate of 63.8 per 100 person-years in the VKA group, 26.2 per 100 person-years in the rivaroxaban group, and 21.4 per 100 person-years in the rivaroxaban and vitamin K2 group. The estimated competing risk-adjusted hazard ratio for the primary end point was 0.41 (95% CI, 0.25 to 0.68; P=0.0006) in the rivaroxaban group and 0.34 (95% CI, 0.19 to 0.61; P=0.0003) in the rivaroxaban and vitamin K2 group, compared with the VKA group. Death from any cause, cardiac death, and risk of stroke were not different between the treatment arms, but symptomatic limb ischemia occurred significantly less frequently with rivaroxaban than with VKA. After adjustment for competing risk of death, the hazard ratio for life-threatening and major bleeding compared with the VKA group was 0.39 (95% CI, 0.17 to 0.90; P=0.03) in the rivaroxaban group, 0.48 (95% CI, 0.22 to 1.08; P=0.08) in the rivaroxaban and vitamin K2 group and 0.44 (95% CI, 0.23 to 0.85; P=0.02) in the pooled rivaroxaban groups. CONCLUSIONS: In patients on hemodialysis with atrial fibrillation, a reduced dose of rivaroxaban significantly decreased the composite outcome of fatal and nonfatal cardiovascular events and major bleeding complications compared with VKA. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Oral Anticoagulation in Hemodialysis, NCT03799822.

Rivaroxaban monotherapy versus combination therapy according to patient risk of stroke and bleeding in atrial fibrillation and stable coronary disease: AFIRE trial subanalysis.

BACKGROUND: In the AFIRE trial, rivaroxaban monotherapy was noninferior to combination therapy with rivaroxaban and an antiplatelet agent for thromboembolic events or death, and superior for major bleeding in patients with atrial fibrillation (AF) and stable coronary artery disease. Little is known about impacts of stroke and bleeding risks on the efficacy and safety of rivaroxaban monotherapy. METHODS: In this subanalysis of the AFIRE trial, we assessed the risk of stroke and bleeding by the CHADS2, CHA2DS2-VASc, and HAS-BLED scores. The primary efficacy end point was the composite of stroke, systemic embolism, myocardial infarction (MI), unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding defined by the International Society on Thrombosis and Haemostasis. RESULTS: Rivaroxaban monotherapy significantly reduced the primary efficacy and safety end points with no evidence of differential effects by stroke risk (CHADS2, p for interaction = 0.727 for efficacy, 0.395 for safety; CHA2DS2-VASc, p for interaction = 0.740 for efficacy, 0.265 for safety) or bleeding risk (HAS-BLED, p for interaction = 0.581 for efficacy, 0.225 for safety). There was also no evidence of statistical heterogeneity across patient risk categories for other end points; stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, MI, MI or unstable angina, death from any cause, any bleeding, or net adverse clinical events. CONCLUSIONS: The advantages of rivaroxaban monotherapy compared with those of combination therapy with respect to all prespecified end points, including thromboembolism, bleeding, and mortality were similar across patients with AF and stable coronary artery disease, irrespective of their risk for stroke and bleeding. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry number, UMIN000016612, and ClinicalTrials.gov number, NCT02642419.

[Antithrombotic therapy after peripheral revascularization]. / Antithrombotische Therapie nach peripherer Revaskularisation.

Patients with lower extremity arterial disease are at increased risk for cardiovascular events. Antithrombotic therapy improves prognosis in these patients especially after peripheral revascularization. After endovascular revascularization duale anti-platelet therapy with Aspirin and Clopidogrel is used for up to 3 months in most cases, although there is only little evidence for this practice. Following peripheral bypass grafting most guidelines recommend single anti-platelet therapy. In some patients, anticoagulation with Vitamin K antagonists or dual anti-platelet therapy is indicated. But this practice is also based on small studies. The Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease (VOYAGER PAD) study is the largest randomized trial concerning antithrombotic therapy after peripheral revascularization. In total 6564 patients were included after successful surgical or endovascular lower-extremity revascularization. Rivaroxaban 2.5 mg twice daily plus Aspirin 100 mg reduced cardiac and peripheral events compared with Aspirin 100 mg alone with increased risk for relevant but not for critical bleeding complications. In addition to antithrombotic medication risk factor management and regular follow-up examinations are important improve long-term prognosis after peripheral revascularization.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Eligibility for Low-Dose Rivaroxaban Based on the COMPASS Trial: Insights from the Veterans Affairs Healthcare System.

INTRODUCTION: Low-dose rivaroxaban reduced major adverse cardiac and limb events among patients with stable atherosclerotic vascular disease (ASCVD) in the COMPASS trial. The objective of our study was to evaluate the eligibility and budgetary impact of the COMPASS trial in a real-world population. METHODS: The VA administrative and clinical databases were utilized to conduct a cross-sectional study to identify patients eligible for low-dose rivaroxaban receiving care at all 141 facilities between October 1, 2014 and September 30, 2015. Proportion of patients with stable ASCVD eligible for low-dose rivaroxaban and prevalence of multiple risk enrichment criteria among eligible patients. Pharmaceutical budgetary impact using VA pharmacy pricing. Chi-squared and Student's t tests were used to compare patients eligible versus ineligible patients. RESULTS: From an initial cohort of 1,248,214 patients with ASCVD, 488,495 patients (39.1%) met trial eligibility criteria. Eligible patients were older (74.2 vs 64.5 years) with higher proportion of hypertension (84.1% vs 82.1%) and diabetes (46.2% vs 32.9) compared with ineligible patients (p < 0.001 for all comparisons). A median of 38.7% (IQR 4.6%) of total ASCVD patients per facility were rivaroxaban eligible. Estimated annual VA pharmacy budgetary impact would range from $0.47 billion to $1.88 billion for 25% to 100% treatment penetration. Annual facility level pharmaceutical budgetary impact would be a median of $12.3 million (IQR $8.0-$16.3 million) for treatment of all eligible patients. Among eligible patients, age greater than 65 years was the most common risk enrichment factor (86.9%). Prevalence of eligible patients with multiple enrichment factors varied from 34.2% (one factor) to 6.2% (four or more). CONCLUSION: Over one third of patients with stable ASCVD may qualify for low-dose rivaroxaban within the VA. Additional studies are needed to understand eligibility in other populations and a formal cost-effectiveness analysis is warranted.