Revised SPC: Xarelto (rivaroxaban) – all strengths

electronic Medicines Compendium

A new paragraph on neuraxial (epidural/spinal) anaesthesia has been added to section 4.4 (all strengths), and new information on patients undergoing cardioversion has been added to sections 4.2 and 5.1 (15mg and 20mg strengths).



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Rivaroxaban for acute coronary syndrome: final appraisal determination

National Institute for Health and Care Excellence

In DRAFTguidance, NICE supports use of rivaroxaban, in combination with aspirin plus clopidogrel or aspirin alone, for preventing atherothrombotic events in people who have had an ACS with elevated cardiac biomarkers. Bleeding risk should be assessed before treatment is started.


Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update 2014

Journal of Clinical Oncology

An evidence update which included a review of 53 publications, found that the 2014 recommendations are consistent with the 2013 recommendations.


Patient Safety Alert (stage one): Harm from using Low Molecular Weight Heparins when contraindicated

NHS England

Consideration of contraindications is a prominent feature of available local and national guidance for prescribing and administering LMWHs. This stage one Patient Safety Alert aims to reinforce the need for reliable systems to ensure that this always occurs.


Dabigatran and Rivaroxaban Use in Atrial Fibrillation Patients on Hemodialysis


A US report found approx 5.9% of end-stage renal disease patients with AF are started on dabigatran or rivaroxaban despite the drugs being contraindicated in these patients; both were associated with a higher risk of hospitalisation or death from bleeding compared to warfarin.



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Characterizing Major Bleeding in Patients With Nonvalvular Atrial Fibrillation: A Pharmacovigilance Study of 27 467 Patients Taking Rivaroxaban

Clinical Cardiology

In a large observational study of 27,467 patients on rivaroxaban, the major bleeding rate (496 events in 478 patients; incidence of 2.86 per 100 person-years) was generally consistent with the registration trial results, and fatal bleeds were rare (0.08 per 100 person-years).


Phase IV study of Factor Xa inhibitor antidote andexanet alfa initiated to support US accelerated approval

Biospace Inc.

A Phase IV study of the investigational Factor Xa inhibitor antidote andexanet alfa in patients receiving apixaban, rivaroxaban or enoxaparin who present with an acute major bleed has been initiated to support its approval by the FDA under an Accelerated Approval pathway.


Ultrasound enhanced catheter-directed thrombolysis for pulmonary embolism: consultation

National Institute for Health and Care Excellence

This DRAFT guidance states there is inadequate evidence of any enhancement of thrombolysis with ultrasound-enhanced, catheter-directed thrombolysis (CDT) over CDT alone for PE; it should only be used with special arrangements for clinical governance, consent and audit or research.


Is Prophylactic Anticoagulation for Deep Venous Thrombosis Common Practice After Intracerebral Hemorrhage?


US analysis (n=32,690 with intracerebral haemorrhage) found <20% receive prophylactic anticoagulation for DVT during hospital stay, even though this is safe to do after cessation of haematoma growth, and when used, time to initiation is <2 days in less than half of patients.



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Anticoagulation during pregnancy in women with prosthetic valves: evidence, guidelines and unanswered questions


Managementof this patient group remains difficult and controversial. There is no ideal anticoagulation regimen as there are inherent risks and benefits of each approach for both mother and foetus. There are limited data on optimal treatment strategy for an individual patient.


FDA approves licensing of edoxaban (Savaysa) tablets

US Food and Drug Administration

The FDA has approved edoxaban, a factor Xa inhibitor, to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.


d-Dimer Testing to Select Patients With a First Unprovoked Venous Thromboembolism Who Can Stop Anticoagulant Therapy: A Cohort Study

Annals of Internal Medicine

This cohort study found a 6.7% per patient-year (PPY) risk for recurrent VTE in patients with a first unprovoked proximal DVT or PE who had a negative d-dimer test result during anticoagulant therapy and 1 month after withdrawal; the recurrence risk was higher in men (9.7% PPY).


Misperceptions of aspirin efficacy and safety may perpetuate anticoagulant underutilization in atrial fibrillation

European Heart Journal

The authors of this discussion conclude it may be necessary to exclude aspirin for stroke prevention in AF (without comorbid conditions requiring its use) from all AF guidelines, as done by NICE, to remove the 'soft option' of prescribing a drug that is neither effective nor safe.



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Biologics license application submitted to FDA for BAX111 for the treatment of Von Willebrand Disease

Biospace Inc.

BAX111 is the first highly-purified recombinant von Willebrand Factor in clinical development, as a treatment option for patients with von Willebrand disease. BAX111 has orphan-drug designation in the EU.


Supplemental New Drug Application submitted to FDA for use of eltrombopag for treatment of chronic ITP in children

Biospace Inc.

The license extension application will be for use in children aged over 6 years who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Currently, eltrombopag is not licensed in any country for treatment of chronic ITP in the paediatric setting.


Duration of Anticoagulation for Venous Thromboembolic Events


This review, based on a case vignette, discusses the evidence for anticoagulant selection and the recommended duration of therapy in patients presenting with venous thromboembolic events



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Outpatient versus inpatient treatment for acute pulmonary embolism

Cochrane Database of Systematic Reviews

Current very low quality evidence from one published RCT did not provide sufficient evidence to assess efficacy and safety of outpatient versus inpatient treatment for acute PE in overall mortality, bleeding and recurrence of PE adequately.


A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke

New England Journal of Medicine

RCT (n=500) found intraarterial treatment (IAT) given within 6 hours after stroke led to shift in distribution of score on modified Rankin scale at 90 days vs. usual care in favour of IAT (OR 1.67; 95% CI, 1.21 to 2.30) and likewise in proportion who were functionally independent.


Biologics License Application submitted to FDA for recombinant Factor VIII (BAY 81-8973) for the treatment of haemophilia A in adults and children

Biospace Inc.

The submission was based on results from the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials, which evaluated rFVIII administered in two-to-three-times-per-week prophylaxis dosing regimens.


Dabigatran etexilate for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism – guidance (TA327)

National Institute for Health and Care Excellence

Dabigatran etexilate is recommended, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults.


Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial

European Heart Journal

In the ARISTOTLE study, major bleeds were associated with an increased risk of death, ischaemic stroke, or MI, especially following intracerebral haemorrhage. This risk was similarly elevated regardless of whether the patient was treated with apixaban or warfarin.



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Use and Outcomes Associated with Bridging During Anticoagulation Interruptions in Patients with Atrial Fibrillation: Findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)

This study noted that bridging anticoagulation is used in a-quarter of anticoagulation interruptions and is linked to higher risk for bleeding (5.0 vs. 1.3%, OR 3.84, p<0.0001) and adverse events (13 vs. 6.3%; OR 1.94, p=0.0001) vs. non-bridging.


Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis

New England Journal of Medicine

RCT in 300 patients found FXI-ASO was non-inferior (200mg OD) or superior (300mg OD) to enoxaparin 40mg OD daily in prevention of VTE in patients undergoing total knee arthroplasty (VTE in 27%, 4% and 30%; and bleeding in 3%, 3%, and 8%; respectively).


Conference report: Phase I study reports idarucizumab reverses anticoagulant effects of dabigatran in middle-aged, elderly and renally impaired volunteers

Biospace Inc.

Administration of idarucizumab in these groups (n=46) resulted in immediate, complete and sustained reversal of the anticoagulation effects of dabigatran. Anticoagulation was restored when volunteers were re-dosed with dabigatran 24 hours after idarucizumab was administered.




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Meta-analysis on Risk of Bleeding with Apixaban in Patients with Renal Impairment

American Journal of Cardiology

In 6 trials (n= 40,145), risk of bleeding with apixaban in patients with mild renal impairment (RI) was significantly less (RR, 0.80; 95% CI, 0.66 to 0.96) vs. conventional anticoagulants, but was similar in patients with moderate-severe RI (1.01; 0.49 to 2.10).


Warfarin Versus Novel Oral Anticoagulants: How to Choose?


This article for patient describes the differences between NOACs and warfarin, use of NOACs for mechanical heart valves and how to select an agent.


Effect of Alteplase Within 6 Hours of Acute Ischemic Stroke on All-Cause Mortality (Third International Stroke Trial)


This exploratory analysis of RCT (n=3035) examining whether long-term survival varied by baseline characteristics after alteplase treatment supports improving acute stroke patients' access to earlier (<3 vs. 3–6 hours) alteplase treatment and treating those with poor prognosis.


Thrombolysis and clinical outcome in patients with stroke after implementation of the Tyrol Stroke Pathway: a retrospective observational study

The Lancet Neurology

This pathway provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation, leading to an increase in use of thrombolysis and an improvement in clinical outcome, although mortality did not change.



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CHMP issues positive opinion on licensing of vorapaxar (Zontivity) in EU

European Medicines Agency

Vorapaxar 2mg film tablet is intended for the reduction of atherothrombotic events in adult patients with a history of MI and should be co-administered with aspirin, and where appropriate, with clopidogrel.


Six-month versus 24-month dual antiplatelet therapy after implantation of drug eluting stents in patients non-resistant to aspirin: ITALIC, a randomized multicenter trial

Journal of the American College of Cardiology

This RCT, terminated early due to recruitment problems (n=2031 of planned 2475) found rates of bleeding and of thrombotic events were not significantly different for 6- vs. 24-month dual antiplatelet therapy after PCI with new-generation DES in aspirin responders.


Percutaneous Left Atrial Appendage Closure vs Warfarin for Atrial Fibrillation: A Randomized Clinical Trial

Journal of the American Medical Association

This study found mechanical left atrial appendage closure to be non-inferior and superior to warfarin in patients with nonvalvular AF and CHADS2 score ≥1 in preventing the combined outcome of stroke, systemic embolism and CV death (rate of 2.3 v 3.8 events per 100 patient-years).


Interim data on dabigatran versus warfarin for AF in routine care

Biospace Inc.

An interim analysis of two health insurance databases show that patients with non-valvular AF treated with dabigatran had a lower rate of major haemorrhage (354 v 395 events; HR 0.75) and stroke (62 v 69; HR 0.77, not statistically significant) vs. those receiving warfarin.


Ponatinib (Iclusig▼): risk of vascular occlusive events

Medicines and Healthcare products Regulatory Agency

An EU review on the risk of serious vascular occlusive events with ponatinib has been completed. The available evidence shows that the risk is likely to be dose-dependent; however the data are insufficient to recommend reducing the ponatinib dose.


Relation of Nonsteroidal Anti-inflammatory Drugs to Serious Bleeding and Thromboembolism Risk in Patients With Atrial Fibrillation Receiving Antithrombotic Therapy: A Nationwide Cohort Study

Annals of Internal Medicine

In patients with AF receiving anticoagulants, exposure to NSAIDs increased the risk of serious bleeding (additional 1.9 events per 1000 patients). The majority of events (38.7%) were gastrointestinal; 18.9% were intracranial. Thromboembolism risk was also increased.


Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate


In this randomised, placebo-controlled Phase 1 study (n=110), a 4-factor prothrombin complex concentrate reversed the effects of edoxaban on bleeding duration following punch biopsy in a dose-dependent manner, with complete reversal observed following 50 IU/kg.


Effects of Golden Hour Thrombolysis: A Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) Substudy

JAMA Neurology

The availability of a stroke emergency mobile unit increased rates of thrombolysis overall (32.6% v 22% with conventional care; P<0.001) and the rates delivered within the first 'golden hour' after symptom onset (31.0% v 4.9%; P<0.01). Short-term mortality rates were similar.

Controversies in cardiovascular medicine – pre-treatment with P2Y12 inhibitors in NSTEMI


Two linked articles discuss whether pre-treatment with P2Y12 inhibitors in Non–ST-segment–elevation acute coronary syndrome is clinically justified.


Extended duration dual antiplatelet therapy and mortality: a systematic review and meta-analysis

The Lancet

This analysis of 14 trials that randomised participants to different durations of dual antiplatelet therapy (DAPT) did not find any difference in all-cause, cardiovascular (CV) or non-CV mortality between extended duration and short-duration DAPT (≤6 months) or aspirin alone.


Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents

New England Journal of Medicine

Patients with a drug-eluting stent who continued dual antiplatelet therapy >1 year had a lower risk of stent thrombosis and major adverse cardiovascular and cerebrovascular events, but increased all-cause mortality (secondary endpoint; HR 1.36; 95% CI, 1.00 to 1.85; P=0.05).



The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service. Further details on this service can be found at:

Development of investigational antibody MEDI2452 for reversal of antiplatelet effects of ticagrelor

Biospace Inc.
A pre-clinical development program is evaluating the ability of MEDI2452 to rapidly and specifically reverse the antiplatelet effects of ticagrelor in emergency situations that cause major bleeding, such as surgery.


Anticoagulant therapy during primary percutaneous coronary intervention for acute myocardial infarction: a meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors

British Medical Journal

In patients with STEMI undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor (GPI) and LMWH plus GPI were most efficacious in terms of avoiding major adverse cardiovascular events in the short-term; bivalirudin was associated with the lowest bleeding risk.


Platelet Transfusion: A Clinical Practice Guideline From the AABB

Annals of Internal Medicine

These US guidelines provide pragmatic recommendations on the appropriate use of platelet transfusion (prophylactic and therapeutic) in adults, based on the best available published evidence.


Vitamin K for Patients with High International Normalized Ratios (INRs): Safety

Canadian Agency for Drugs and Technologies in Health

A limited literature search identified one non-randomised study which found that withholding warfarin or giving vitamin K treatment to patients on oral anticoagulants who have an INR >9 did not effectively reduce the INR within 24 hours.


RAC recommends further assessment of risk of developing inhibitors with Kogenate Bayer/Helixate NexGen (factor VIII)

European Medicines Agency

The PRAC is recommending further examination of the available evidence for Kogenate Bayer/Helixate NexGen, as new evidence has shown it may be associated with a higher risk of inhibitor (antibody) development than other FVIII products in treatment-naïve haemophilia patients.



The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service. Further details on this service can be found at: