Chronic Limb-Threatening Ischemia ; Factor Xa Inhibitors/adverse effects* ; Humans ; Platelet Aggregation Inhibitors/adverse effects* ; Rivaroxaban/adverse effects* ; Singapore ; Treatment Outcome

Objective: This analysis was performed to evaluate the efficacy and the safety of rivaroxaban-aspirin combination therapy in secondary prevention of major adverse cardiovascular events in Chinese patients enrolled in the COMPASS trial. Methods: COMPASS was a prospective, international multi-center and randomized controlled trial. From September 2014 to February 2017, 1 086 patients with stable coronary artery disease and peripheral artery diseases were recruited from 31 centers in China. Patients were randomly assigned to separately receive the therapy of rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day,) group (n=366), rivaroxaban (5 mg twice a day) alone group (n=365), and aspirin (100 mg once a day) alone group (n=355). Baseline information such as age, sex, etc. of all three groups was collected. Finally, 1 081 patients were followed up successfully, with the follow-up rate 99.5% and the average follow-up time was 19 months. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction and stroke. The primary safety endpoint was major bleeding evaluated by modified International Society on Thrombosis and Haemostasis criteria. Results: Age of patients was (64.2±8.3) years and there were 293 male in rivaroxaban plus aspirin group. Age of patients was (63.8±9.0) years, and there were 301 male patients in rivaroxaban alone group. Age of patients was (63.6±8.8) years, and there were 282 male patients in the aspirin alone group. The incidences of primary efficacy endpoint occurred in 9 cases (1.5%) in rivaroxaban with aspirin group, 21 cases (3.7%) in rivaroxaban alone group and 14 cases (2.5%) in aspirin alone group. Meanwhile, the incidences of primary safety endpoint occurred in 6 cases (1.0%) in rivaroxaban with aspirin group, 9 cases (1.6%) in rivaroxaban alone group and 7 cases (1.2%) in aspirin alone group. The net clinical benefit events were 10 cases (1.7%) in rivaroxaban with aspirin group, 22 cases (3.9%) in rivaroxaban alone group and 15 cases (2.7%) in aspirin alone group (P>0.5%). Conclusions: The combination of rivaroxaban with aspirin can be safe and effectively used for the secondary prevention in Chinese patients with stable coronary artery disease and peripheral artery diseases.
Aged ; Aspirin/therapeutic use* ; Cardiovascular Diseases/prevention & control* ; China ; Drug Therapy, Combination ; Factor Xa Inhibitors/therapeutic use* ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/therapeutic use* ; Prospective Studies ; Rivaroxaban/therapeutic use* ; Secondary Prevention

Anticoagulants ; Antithrombins/therapeutic use* ; Coronary Disease ; Heparin ; Hirudins ; Humans ; Peptide Fragments ; Percutaneous Coronary Intervention ; Recombinant Proteins ; Treatment Outcome

Abdominal Injuries ; Antithrombins/adverse effects* ; Atrial Fibrillation ; Dabigatran/adverse effects* ; Humans ; Thoracic Injuries

BACKGROUND: Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE. METHODS: Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality. RESULTS: Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (P = 0.074). No inter-group difference was observed for rate of VTE recurrence (3.8% with rivaroxaban vs. 3.9% with LMWH; P > 0.999) or incidence of major bleeding (5.1% with rivaroxaban vs. 8.9% with LMWH; P = 0.296). Multivariate Cox proportional hazards analysis for age, cancer type, metastasis, history of chemotherapy or recent surgery, and Eastern Cooperative Oncology Group performance status revealed a 1.904-fold higher risk of bleeding with rivaroxaban than LMWH (1.031–3.516; P = 0.040). No significant inter-group difference was found in terms of hazard ratio for all-cause mortality. CONCLUSION: Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.
Colorectal Neoplasms ; Drug Therapy ; Factor Xa Inhibitors ; Gastrointestinal Tract ; Hemorrhage ; Heparin, Low-Molecular-Weight ; Humans ; Incidence ; Mortality ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies ; Rivaroxaban ; Stomach Neoplasms ; Venous Thromboembolism

PURPOSE: Comparisons of rhythm and rate control strategies for stroke prevention in patients with atrial fibrillation (AF) are still inconclusive. We compared differences in clinical outcomes between the rhythm and rate control strategies. MATERIALS AND METHODS: The COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry prospectively enrolled 6000 patients who were treated for AF using real-world guideline adherence at multiple referral centers. In total, 2508 (41.8%) patients were clinically followed up for over six months. Of these, 1134 (45.2 %) patients treated by rhythm control and 1374 (54.8 %) patients treated by rate control were analyzed for clinical outcomes, including stroke and cardiovascular outcomes. RESULTS: Among all patients (age, 68±10 years; male, 62.4%), those treated with the rhythm control strategy were significantly younger, had more symptomatic paroxysmal AF, and a shorter AF duration, and were less likely to have diabetes, renal dysfunction, and heart failure, compared to those treated with the rate control strategy (CHA₂DS₂-VASc score 2.4±1.5 vs. 3.1±1.7, p < 0.001). Even though oral anticoagulation was similarly prescribed in both groups, occurrence of stroke was less likely to occur in the rhythm control strategy group (0.0% vs. 0.7%, p=0.015). Multivariate Cox hazard regression showed that only age, especially more than 75 years old, were significantly correlated with the occurrence of stroke, regardless of the strategy used for treatment. CONCLUSION: In this prospective AF cohort, compared with the rate control strategy, the rhythm control strategy was associated with fewer cardiovascular events and strokes in a short-term period.
Administration, Oral ; Aged ; Antithrombins/administration & dosage/therapeutic use ; Atrial Fibrillation/drug therapy/*physiopathology ; Female ; Heart Rate/*physiology ; Humans ; Kaplan-Meier Estimate ; Male ; Proportional Hazards Models ; Prospective Studies ; Stroke/drug therapy/*etiology/*physiopathology ; Treatment Outcome

Regulatory approvals of non-vitamin K antagonist oral anticoagulants (NOACs) have been based on large randomized phase III trials evaluating dabigatran, rivaroxaban, apixaban, or edoxaban relative to warfarin for atrial fibrillation (AF). The results of the trials showed that all NOACs were at least non-inferior to warfarin in the prevention of stroke/thromboembolism and showed lower rates of intracranial bleeding than those associated with warfarin. However, the trials were designed differently, varied in the inclusion/exclusion criteria, and used either one dose or a low/high dose of the NOAC drug. Some of these differences have challenged the ability to directly compare various NOACs, and comparative data on effectiveness and intracranial bleeding are sparse in “real-world” patients. Real-world data complement data from large randomized phase III trials by providing new aspects of the “real-world” absolute risks of ischemic and hemorrhagic stroke associated with NOACs vs. warfarin. Moreover, “real-world” fragile patients might have been included (e.g., patients with increased risk of bleeding, liver disease, and chronic kidney disease), although these patients would be less represented in trials. This paper introduces recently published real-world data of NOACs and further suggests the recommended dosage of NOACs for Korean patients.
Anticoagulants* ; Atrial Fibrillation ; Complement System Proteins ; Dabigatran ; Factor Xa Inhibitors ; Hemorrhage ; Humans ; Kidney ; Liver Diseases ; Rivaroxaban ; Stroke ; Warfarin

Heparin-induced thrombocytopenia (HIT) is a serious, immune mediated complication of exposure to unfractionated or low-molecular-weight heparin. Though rare, it is a condition associated with high morbidity and mortality that requires immediate change to alternative anticoagulants for the prevention of life-threatening thrombosis. The direct thrombin inhibitors lepirudin and argatroban are currently licensed for the treatment of HIT. Dabigatran, a novel oral anticoagulant (NOAC) with a similar mechanism of action and effective use in other indications, has recently been proposed as another therapeutic option in cases of HIT. This review serves as an introduction to using dabigatran for this purpose, detailing the clinical aspects of its administration, evidence of its performance compared to other anticoagulants, and the preliminary reports of HIT successfully treated with dabigatran. As the literature on this develops, it will need to include clinical trials that directly evaluate dabigatran against the other NOACs and current treatment options.
Anticoagulants ; Antithrombins ; Dabigatran* ; Heparin, Low-Molecular-Weight ; Mortality ; Thrombocytopenia* ; Thrombosis

INTRODUCTIONDirect oral anticoagulants (DOACs) are establishing themselves as principle choices for the treatment of a variety of thrombotic disorders. DOACs are also known to affect common coagulation tests which are routinely performed for patients in clinical practice. An understanding of their varied effects is crucial for the appropriate ordering of coagulation tests and their interpretation.

MATERIALS AND METHODSLaboratories in public and private healthcare institutions and commercial sectors were surveyed on coagulation tests offered and their methods. A Medline and bibliography search, including a search on search engines, was performed for publications reporting the effects of dabigatran, apixaban and rivaroxaban on these coagulation tests. These papers were reviewed and summarised for consensus recommendations.

RESULTSProthrombin time (PT) and activated partial thromboplastin time (aPTT) are variably affected by the DOACs and dependent of the coagulation assays used. Clinicians must know which laboratory has performed these tests to logically interpret test results. A normal PT or aPTT does not exclude the presence of residual DOACs effect. The thrombin time is sensitive to dabigatran but not apixaban or rivaroxaban. Specialised coagulation tests such as thrombophilia tests are also variably affected by the DOACs. All laboratories in Singapore however, employ similar test methods permitting a common set of recommendations for specialised coagulation testing.

CONCLUSIONKnowledge of the effects of DOACs on coagulation testing is essential to determine the appropriateness of performing such tests and interpreting them coherently. Practical recommendations which are tests and location-specific are set out in this paper.

Antithrombins ; therapeutic use ; Blood Coagulation Tests ; Dabigatran ; therapeutic use ; Factor Xa Inhibitors ; therapeutic use ; Humans ; Partial Thromboplastin Time ; Practice Guidelines as Topic ; Prothrombin Time ; Pyrazoles ; therapeutic use ; Pyridones ; therapeutic use ; Rivaroxaban ; therapeutic use ; Singapore

Cirrhosis can occur with the development of portal vein thrombosis (PVT). PVT may aggravate portal hypertension, and it can lead to hepatic decompensation. The international guideline recommends for anticoagulation treatment to be maintained for at least 3 months in all patients with acute PVT. Low-molecular-weight-heparin and changing to warfarin is the usual anticoagulation treatment. However, warfarin therapy is problematic due to a narrow therapeutic window and the requirement for frequent dose adjustment, which has prompted the development of novel oral anticoagulants for overcoming these problems. We report a 63-year-old female who experienced complete resolution of recurrent acute PVT in liver cirrhosis after treatment with rivaroxaban.
Administration, Oral ; Factor Xa Inhibitors/*therapeutic use ; Female ; Humans ; Liver Cirrhosis/*complications/diagnosis ; Middle Aged ; Portal Vein ; Recurrence ; Rivaroxaban/*therapeutic use ; Tomography, X-Ray Computed ; Venous Thrombosis/complications/diagnostic imaging/*drug therapy