OBJECTIVE: Anticoagulation can prevent stroke and prolong lives in patients with atrial fibrillation (AF); However, anticoagulated patients with AF remain at risk of death. The aim of this study was to investigate the causes of death and factors associated with all-cause and cardiovascular death in the XANTUS population.
RESULTS: Causes of death occurring within a year after rivaroxaban initiation in patients in the XANTUS program studies were adjudicated by a central adjudication committee and classified following international guidance.Baseline characteristics associated with all-cause or cardiovascular death were identified. Of 11,040 patients, 187 (1.7%) died. Almost half of these deaths were due to cardiovascular causes other than bleeding (n = 82, 43.9%), particularly heart failure (n = 38, 20.3%) and sudden or unwitnessed death (n = 24, 12.8%). Fatal stroke (n = 8, 4.3%), which was classified as a type of cardiovascular death, and fatal bleeding (n = 17, 9.1%) were less common causes of death. Independent factors associated with all-cause or cardiovascular death included age, AF type, body mass index, left ventricular ejection fraction, hospitalization at baseline, rivaroxaban dose, and anaemia.
CONCLUSIONS: The overall risk of death due to stroke or bleeding was low in XANTUS. Anticoagulated patients with AF remain at risk of death due to heart failure and sudden death. Potential interventions to reduce cardiovascular deaths in anticoagulated patients with AF, require further investigation, e.g. early rhythm control therapy and AF ablation.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly prescribed for life-long anticoagulation in chronic thromboembolic pulmonary hypertension (CTEPH) patients, despite not being recommended in the guidelines. This study aims to evaluate the efficacy and safety of DOACs in CTEPH patients.
METHODS: From May 2013 to December 2022, patients who were first diagnosed with CTEPH in Fuwai Hospital and started long-term anticoagulation treatment with warfarin or DOACs were retrospectively included and followed up until (1) death, (2) transition to other kinds of anticoagulants, or (3) discontinuation of anticoagulation. Propensity score matching was used to balance confounding bias of baseline characteristics. All-cause death, major bleeding, clinically relevant nonmajor bleeding and venous thromboembolism (VTE) recurrence were obtained and analysed.
RESULTS: After propensity score matching, 115 patients taking warfarin and 206 patients taking DOACs were included in our study and followed up for 5.5 [3.4, 7.1] years. There was no significant difference of survival between the warfarin and the DOAC group (p = 0.77). The exposure adjusted event rate of major bleeding (0.3%/person-year vs 0.4%/person-year, p = 0.705) and clinically relevant nonmajor bleeding (3.1%/person-year vs 3.2%/person-year, p > 0.999) was similar between two groups. The exposure adjusted rate of VTE recurrence was significantly higher in the DOAC group (1.5%/person-year vs 0.3%/person-year, p = 0.030).
CONCLUSIONS: In anticoagulation of CTEPH patients, DOACs have similar survival rate, similar risk of bleeding but higher risk of VTE recurrence than warfarin.

UNASSIGNED: Unusual site deep vein thrombosis (DVT) was defined as venous thromboembolism (VTE) occurring outside the conventional deep veins of the lower extremity or pulmonary arteries. However, the optimal anticoagulation therapy for unusual site DVT remained unclear. This study aims to evaluate the efficacy and safety of rivaroxaban in unusual site DVT.
UNASSIGNED: This retrospective cohort study enrolled consecutive patients at Nanjing Drum Tower Hospital between January 2011 and December 2021 who were diagnosed with unusual site DVT. Patients were divided into two groups based on their ultimate medication choice: the warfarin group and the rivaroxaban group. The demographic characteristics were recorded for all enrolled patients. Clinical outcomes included recurrent VTE, bleeding complications and major bleeding.
UNASSIGNED: A total of 1,088 patients were divided into warfarin (n = 514) and rivaroxaban (n = 574) groups. After the stabilized inverse probability of treatment weighting, Hazard Ratios for warfarin vs. rivaroxaban of recurrent VTE, bleeding complications and major bleeding were 0.52(95% CI: 0.25-1.08), 0.30(95% CI: 0.14-0.60), and 0.33 (95% CI, 0.13-0.74), respectively. Risk of clinical outcomes in specified subgroups for age, gender, renal function, thrombosis sites and diagnosis were assessed. The interaction of gender and treatment on major bleeding was significant (P for interaction = 0.062). Otherwise, there was no significant interaction between the other subgroups and the treatment group in terms of clinical outcomes.
UNASSIGNED: Compared with warfarin, rivaroxaban exhibited comparable efficacy for the anticoagulant treatment of unusual site DVT, associated with a lower risk of bleeding complications and major bleeding.

BACKGROUND: This study evaluates the cost-effectiveness of Apixaban and Rivaroxaban, compared to Warfarin, for stroke prevention in patients with non-valvular atrial fibrillation in Iran.
METHODS: A Markov model with a 30-year time horizon was employed to simulate and assess different treatment strategies\' cost-effectiveness. The study population comprised Iranian adults with NVAF, identified through specialist consultations, hospital visits, and archival record reviews. Direct medical costs, direct nonmedical, and indirect costs were included. Quality-adjusted life years (QALY) were assessed using an EQ-5D questionnaire. This study utilized a cost-effectiveness threshold of $11 134 per QALY.
RESULTS: Apixaban demonstrated superior cost-effectiveness compared to Rivaroxaban and Warfarin. Over 30 years, total costs were lower in the Apixaban and Rivaroxaban groups compared to the Warfarin group ($126.18 and $109.99 vs. $150.49). However, Apixaban showed higher total QALYs gained compared to others (0.134 vs. 0.133 and 0.116). The incremental cost-effectiveness ratio for comparing Apixaban to Warfarin was calculated at -1332.83 cost per QALY, below the threshold of $11 134, indicating Apixaban\'s cost-effectiveness. Sensitivity analyses confirmed the robustness of the findings, with ICER consistently remaining below the threshold. Over 5 years (2024-2028) of Apixaban usage, the incremental cost starts at USD 70 250 296 in the first year and gradually rises to USD 71 770 662 in the fifth year. DSA and PSA were assessed to prove the robustness of the results.
CONCLUSIONS: This study shows that Apixaban is a cost-effective option for stroke prevention in non-valvular atrial fibrillation patients in Iran compared to Warfarin.

BACKGROUND: Direct oral anticoagulants (DOAC) are increasingly used for prophylaxis and treatment of thromboembolic events. Incorrectly dosed DOAC treatment is associated with excess mortality.
OBJECTIVE: This article aims at raising awareness of DOAC overdosing and its causes as well as presenting a diagnostic and therapeutic work-up.
METHODS: Based on a case presentation, a structured review of the current literature on DOAC overdosing was performed and treatment recommendations were extracted.
RESULTS: In addition to wittingly or unwittingly increased DOAC intake, common causes of overdose are inadequate dose adjustment for concomitant medication or comorbidities. Global coagulation testing should be supplemented with DOAC-specific testing. Severe bleeding and the need for invasive diagnostics or urgent surgery represent indications for treating DOAC overdoses. Based on the cause of an DOAC overdose, active charcoal, endoscopic pill rescue, antagonization with idarucizumab or andexanet alfa and the targeted substitution of coagulation factors represent treatment options.
CONCLUSIONS: The sensitization of clinicians is important to ensure a timely diagnosis and adequate treatment of DOAC overdosing. This report provides an overview of current knowledge on diagnostics and treatment; however, further studies are necessary to improve the existing algorithms.
UNASSIGNED: HINTERGRUND: Direkte orale Antikoagulanzien (DOAK) werden zunehmend zur Prophylaxe und Therapie thromboembolischer Ereignisse eingesetzt. Eine fehldosierte DOAK-Therapie ist mit einer Übersterblichkeit verbunden. ZIEL: Der Beitrag möchte für das Problem von DOAK-Überdosierungen sowie deren Ursachen sensibilisieren. Diagnostische und therapeutische Möglichkeiten werden zusammengefasst.
METHODS: Basierend auf einem Fallbeispiel erfolgte die Auswertung der verfügbaren Literatur zum Thema DOAK-Überdosierungen. Hieraus wurden Handlungsempfehlungen abgeleitet.
UNASSIGNED: Häufigste Ursache für DOAK-Überdosierungen ist neben der bewusst oder akzidentell gesteigerten Einnahme eine unzureichende Anpassung der Dosis an Komorbiditäten oder an weitere Medikamente. Globale Gerinnungstests sollten durch DOAK-spezifische Untersuchungen ergänzt werden. Eine schwere Blutung sowie die Notwendigkeit einer invasiven Diagnostik oder einer dringenden Operation stellen Indikationen zur Therapie einer DOAK-Überdosierung dar. Je nach Ursache kommen die Gabe von Aktivkohle, die endoskopische Tablettenbergung, die Antagonisierung mit Idarucizumab oder Andexanet alfa sowie die gezielte Substitution von Gerinnungsfaktoren infrage.
UNASSIGNED: Um eine zeitgerechte Diagnose und adäquate Behandlung von DOAK-Überdosierungen zu gewährleisten, bedarf es der Sensibilisierung der behandelnden Ärzt*innen. Dieser Artikel gibt eine aktuelle Übersicht zu Diagnostik und Therapie, jedoch sind zur Verbesserung der bestehenden Algorithmen weitere Studien notwendig.

UNASSIGNED: Rivaroxaban, a non-vitamin K antagonist oral anticoagulant, has become widely used for the management of venous thromboembolism (VTE) in adult patients. However, few trials have explored the efficacy and safety of rivaroxaban in VTE patients over 80 years of age. This necessitates further real-world studies of rivaroxaban across elderly populations.
UNASSIGNED: We performed a retrospective single center study involving extremely aged VTE sufferers treated with rivaroxaban. The sample comprised 121 patients newly initiated on rivaroxaban diagnosed between January 2018 and January 2020. Patients were followed up for no less than 2 years. The effectiveness outcome was the disappearance of thromboembolism. The safety outcome was the incidence of major bleeding events. Comorbidities and complications were recorded throughout the entire study.
UNASSIGNED: The efficacy outcome occurred in 114 of 121 patients (94.21%) and the safety outcome occurred in 12 of 121 patients (9.91%). Increased hemorrhages were observed in patients with infection (15.15% vs 7.80%), but no significant difference was observed due to limited sample size (P=0.3053). Patients with an age-adjusted Charlson comorbidity index score higher than 6 points exhibited higher bleeding rates (14.08% vs 4.00%; P=0.0676) and lower thrombus cure rates (88.73% vs 100%; P=0.0203).
UNASSIGNED: Patients with infection should be more careful of bleeding events during rivaroxaban therapy. An age-adjusted Charlson comorbidity index score higher than 6, which predicted poor survival, indicated inferior safety and efficacy of rivaroxaban.
UNASSIGNED: To investigate the efficacy and safety of Rivaroxaban in an aged venous thromboembolism patient population under real-world conditions.

The number of patients with atrial fibrillation is increasing, and frailty prevalence increases with age, posing challenges for physicians in prescribing anticoagulants to such patients because of possible harm. The effects of frailty on anticoagulant therapy in older Japanese patients with nonvalvular atrial fibrillation (NVAF) are unclear. Herein, we prescribed rivaroxaban to Japanese patients with NVAF and monitored for a mean of 2.0 years. The primary endpoint was stroke or systemic embolism. The secondary endpoints were all-cause or cardiovascular death, composite endpoint, and major or non-major bleeding. Frailty was assessed using the Japanese long-term care insurance system. A multiple imputation technique was used for missing data. The propensity score (PS) was obtained to estimate the treatment effect of frailty and was used to create two PS-matched groups. Overall, 5717 older patients had NVAF (mean age: 73.9 years), 485 (8.5%) were classified as frail. After PS matching, background characteristics were well-balanced between the groups. Rivaroxaban dosages were 10 and 15 mg/day for approximately 80% and the remaining patients, respectively. Frailty was not associated with the primary endpoint or secondary endpoints. In conclusion, frailty does not affect the effectiveness or safety of rivaroxaban anticoagulant therapy in older Japanese patients with NVAF.Trial registration: UMIN000019135, NCT02633982.

The gold standard therapy for end-stage heart failure is cardiac transplantation. However, in the face of a donor shortage, a mechanical assist device such as the left ventricular assist device HeartMate 3 (Abbott Laboratories, Abbott Park, IL, USA) serves as bridging therapy to transplantation and/or destination therapy. Current guidelines recommend anticoagulation with a vitamin K antagonist in combination with low-dose aspirin. We herein report a challenging anticoagulation regimen in a patient with a HeartMate 3 in whom systemic anticoagulation with warfarin was not feasible for 4 years because of low compatibility and a rare X-factor deficiency. This is a rare hematological disorder, estimated to affect approximately 1 in every 500,000 to 1,000,000 people in the general population. The patient finally received a modified anticoagulation regimen involving the combination of rivaroxaban and clopidogrel without warfarin. Under this regimen, the patient remained free of thromboembolic complications for 4 years with in situ placement of the left ventricular assist device. This case illustrates that under specific circumstances, long-term absence of warfarin therapy is feasible in patients with a HeartMate 3.

UNASSIGNED: Direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, commonly used direct oral anticoagulant (DOAC), are widely used to prevent and treat stroke and venous thromboembolic events in patients with atrial fibrillation (AF). This study aimed to assess and compare reports of adverse events associated with rivaroxaban, apixaban, and edoxaban, including hemorrhagic and non-hemorrhagic events.
UNASSIGNED: Reporting odds ratio (ROR), proportional reporting ratio (PRR), Medications and Health Care Products Regulatory Agency (MHRA), and the information component (IC) were used to perform a risk assessment of adverse event reports in the FDA Adverse Event Reporting System (FAERS) database for the years 2018-2022.
UNASSIGNED: Combined with disproportionality analysis in different backgrounds, the salient risks of the three-factor Xa inhibitors varied. Rivaroxaban had the most significant risk of hemorrhage, apixaban had a higher incidence and risk of death, cardiac and cerebral adverse events, and edoxaban showed a more prominent risk in the kidneys and urinary system.
UNASSIGNED: Hemorrhage is a common risk with factor Xa inhibitors, with rivaroxaban being the most significant. Apixaban and edoxaban also showed significant association with non-hemorrhagic adverse events, and increased attention to non-hemorrhagic adverse events is needed in clinical use.

BACKGROUND: There are no clinical trials with head-to-head comparison between the two 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 among older patients who are at the highest risk for stroke and bleeding.
OBJECTIVE: To compare the risk of major bleeding and thromboembolic events with apixaban versus rivaroxaban in older patients with AF.
METHODS: 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 (IPTW).
RESULTS: This study included 42,617 patients with AF treated with apixaban and 30,725 patients treated with rivaroxaban. After IPTW using the propensity score, patients in the apixaban and rivaroxaban groups were well balanced for baseline values of demographics, comorbidities and medications; both groups had similar mean age of 77.4 years and 49.9% were female. At one year, the apixaban group had reduced risk for both major bleeding with an absolute risk reduction at one year of 1.1% (2.1% vs 3.2%; HR 0.65 [95% 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]).
CONCLUSIONS: Among AF patients, 66 years or older, treatment with apixaban was associated with reduced risk for major bleeding with no difference in risk for thromboembolic events compared with rivaroxaban.