Conference report: Updated results from ongoing phase III RE-VERSE AD study on safety and efficacy of idarucizumab (Praxbind) in urgent situations

Biospace Inc.

In trial of 494 patients who had uncontrolled or life-threatening bleeding or required emergency surgery or an invasive procedure, primary endpoint of reversal of anticoagulant effect of dabigatran with 5g of idarucizumab within 4 hours was 100% Reversal was evident immediately.


Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy


Study (n=2124) found either rivaroxaban 15 mg OD+P2Y12 inhibitor monotherapy or 2.5 mg rivaroxaban BD plus dual antiplatelet therapy (DAPT) was associated with a reduced risk of all-cause mortality/recurrent hospitalisation vs standard-of-care vitamin k antagonist+DAPT.


Warfarin utilisation and anticoagulation control in patients with atrial fibrillation and chronic kidney disease


Study (n=123188) found warfarin use decreased with increasing severity of chronic kidney disease (CKD) (57.2%–46.4%), but was higher in patients on dialysis (62.3%). Proportion of patients with time in range (TIR) ≥60% decreased with CKD severity; 21% on dialysis achieved TIR≥60%.


Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI

New England Journal of Medicine

The administration of either low-dose rivaroxaban (R)+P2Y12 inhibitor for 12 months or very-low-dose R+DAPT for 1, 6, or 12 months was associated with a
lower rate of clinically significant bleeding than was standard therapy with a vit K antagonist+DAPT for 1, 6, or 12 months.


Under-prescribing of Prevention Drugs and Primary Prevention of Stroke and Transient Ischaemic Attack in UK General Practice: A Retrospective Analysis

PLOS Medicine

UK study (n=29043) found >50% of people eligible for lipid-lowering, anticoagulant, or antihypertensive drugs were not prescribed them prior to first stroke/TIA. The authors estimate that around 12000 first strokes could be prevented/year annually through optimal prescribing.


Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients: An APEX Trial Substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban)


This study (n=7513) reports that there were fewer all-cause strokes (0.54% v 0.97%; RR=0.56; P=0.032) and ischaemic strokes (0.48% v 0.91%; RR=0.53; P=0.026) among patients treated with betrixaban v enoxaparin through 77 days of follow-up.


Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial

European Heart Journal

Analysis of the TRACER trial (n=12,944) found that MI was associated with a greater risk of mortality compared with Bleeding Academic Research Consortium (BARC) 2 and 3a bleeding; a similar risk of mortality to BARC 3c bleeding; and a lower risk of mortality than BARC 3c bleeding.


Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease

New England Journal of Medicine

RCT (n=13,885) found that ticagrelor is not superior to clopidogrel for reducing cardiovascular events (10.8% vs 10.6%, HR 1.02, 95% CI 0.92-1.13). Major
bleeding occurred at similar rates (1.6% in both groups, HR 1.10, 95% CI 0.84-1.43).


CHMP issues positive opinion for lonoctocog alfa (Afstyla) for treatment and prophylaxis of bleeding in patients with haemophilia A

European Medicines Agency

Lonoctocog alfa is a single-chain recombinant human factor VIII product. It is proposed that the market authorisation extends to use in all age groups.



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:

Association of Traditional Cardiovascular Risk Factors with Venous Thromboembolism: An Individual Participant Data Meta-analysis of Prospective Studies


Meta-analysis (9 studies, n=255,865 with 4910 VTE events) found that apart from the association of cigarette smoking with provoked VTE, modifiable traditional CVD risk factors are not associated with increased risk. Higher systolic blood pressure was inversely associated with VTE.


Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial

The Lancet

This RCT (n=152) showed no significant difference between patients receiving nadroparin v placebo in the composite primary outcome-composite measure of
extension of calf DVT to proximal veins, contralateral proximal DVT and symptomatic PE at day 42 (3% vs 5% respectively, p=0.54).



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:

Short term versus long term dual antiplatelet therapy after implantation of drug eluting stent in patients with or without diabetes: systematic review and meta-analysis of individual participant data from randomised trials

British Medical Journal

Review (n=11,473) found long term (12 months) dual antiplatelet therapy (DAPT) did not reduce risk of major adverse cardiac events vs. short term DAPT (≤6 months) but increased risk of bleeding among patients with stents with or without diabetes.


Association between delivery methods for red blood cell transfusion and the risk of venous thromboembolism: a longitudinal study

The Lancet Haematology

Study (n=10604) found transfusion via a multi-lumen PICC is associated with a greater risk of thrombosis than via a peripheral IV catheter (HR 1•96 (95% CI
1•47–2•61; p<0•0001) vs. patients not receiving a transfusion, and 1•79 (1•09–2•95; p=0•022) vs. peripheral IV line.


Genetic Polymorphisms and Clopidogrel Efficacy for Acute Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-analysis


Review (15 studies, 4762 patients) found carriers of CYP2C19 loss-of-function alleles (*2, *3 and/or *8) were at increased risk of stroke vs non-carriers among patients with ischemic stroke/TIA treated with clopidogrel (12.0 vs. 5.8%; RR 1.92, 95% CI: 1.57-2.35; p<0.001).


Adverse events in trial for haemophilia drug, ACE910

Reuters Health

Four patients have suffered serious adverse events relating to thrombosis/ blood clots in a trial of ACE910. ACE910 is a recombinant bispecific monoclonal
antibody which simultaneously binds factor IXa and X, exerting the same function as factor VIII.


Wide Variation in Reported Rates of Stroke Across Cohorts of Patients with Atrial Fibrillation


This review (34 studies) reports a variation in reported stroke rates in different cohorts of patients with AF showing that CHA2DS2-VASc scores do not
correspond to fixed absolute stroke rates; a net clinical benefit for anticoagulating patients with score 1 or 2 was not observed.



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:

Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: expert consensus paper of the European Society of Cardiology Working Group on Thrombosis

European Heart Journal

While waiting for observational and randomised data to accrue, this consensus paper offers a European perspective on managing antithrombotic therapy after
bleeding in patients with coronary artery disease and/or AF, including which drugs to stop, which to restart, and when.


Patterns of antiplatelet drug use after a first myocardial infarction during a 10-year period

British Journal of Clinical Pharmacology

Trial (n=4690) found persistent users decreased from 84.0% at 1-year to 32.8% at 10 years for any antiplatelet [AP: 77.3% to 27.5% for aspirin; 39.0% to 6.4% for clopidogrel at 6 years]. Most nonpersistent users restarted, leading to 89.3% overall AP users at 10 years post MI.


Medicines Optimisation in Atrial Fibrillation

Specialist Pharmacy Service

First section of this document shows how to use nationally available data to build picture of care and assess quality of AF management for any locality. Second
section provides short review protocol for patients on AF register which can be used to optimise their anticoagulation.


Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation


In this RCT (n=18,140) non-major bleeding was reported less frequently with apixaban (6.4/100 patient-years) than warfarin (9.4/100 patient-years) (adjusted HR 0.69, 95% CI 0.63 to 0.75) and was associated with fewer adverse outcomes including mortality and subsequent major bleed.


Conference report: Two real-world studies confirm positive efficacy and safety profile of rivaroxaban taken for longer than 3 months for venous thromboembolism (VTE)

Biospace Inc.

At 6 months, recurrent VTE occurred in 1.07% of people in the continued cohort and 2.10% in the discontinued cohort (p<0.05) whilst major bleeding occurred in 0.79% and 0.72% respectively (p>0.05). Similar findings were reported at 12 months.


Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery

New England Journal of Medicine

Study (n=4631) found no significant difference in death/thrombotic complications within 30 days of surgery between tranexamic acid and placebo (16.7% vs.
18.1%, respectively). Tranexamic acid was associated with a lower risk of bleeding vs placebo.



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:

AF patients with no schooling benefit least from anticoagulants

European Heart Journal

Survey of more than 1100 patients with atrial fibrillation found those with no schooling missed treatment targets more often, were less aware of bleeding
risks, and did not know they could continue normal daily activities (for example drive, play sports and travel by plane).



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:

Ischaemic and haemorrhagic stroke associated with non-vitamin K antagonist oral anticoagulants and warfarin use in patients with atrial fibrillation: a nationwide cohort study

European Heart Journal

Analysis of registry data (2011–15) found that among 43, 299 anticoagulant-naïve AF patients, treatment with NOACs was not linked to significantly lower risk of stroke/thromboembolism vs. vitamin K antagonist but intracranial bleeding risk was lower with dabigatran and apixaban.


What factors should be considered when using LMWH to treat venous thromboembolism in patients with high body weight?

Specialist Pharmacy Service

This Q&A offers guidance on what factors should be considered when calculating a low molecular weight treatment dose following a venous thromboembolism in non-pregnant adult patients with a high body weight, defined as more than 120kg.


Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial

The Lancet Neurology

In this study of 96 patients, the primary outcomes (30 day mortality, 7 day procedure-related mortality, 72h symptomatic bleeding, and 30 day brain
infections) did not differ between the standard medical care vs minimally invasive surgery + alteplase groups.


FDA analyses conclude that results from ROCKET-AF trial of rivaroxaban were not affected by faulty INR meter

US Food and Drug Administration

In July 2016, Alere INRatio device, which was used to monitor warfarin in control group of trial was recalled due to potential to generate inaccurate results.
Following series of analyses, FDA has determined effects on strokes or bleeding, including cerebral bleeds were minimal.


Real-world comparison of major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin. A propensity matched analysis

Thrombosis and Haemostasis

This study (n=45,361) found that apixaban and dabigatran were associated with a lower risk of major bleeding vs warfarin (HR 0.53, 95% CI 0.39-0.71 and 0.69, 0.50-0.96). Compared to apixaban, rivaroxaban was associated with higher risk of major bleeding (1.82, 1.36-2.43).



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:

Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation

JAMA Internal Medicine

This analysis of 118 891 atrial fibrillation patients taking rivaroxabanor dabigatran reports that those treated with rivaroxaban were more likely to experience both intracranial haemorrhage or major extracranial bleeding than those treated with dabigatran.


The Handbook of Perioperative Medicines

UK Clinical Pharmacy Association

This handbook, in the form of drug monographs, contains information on how medicines are to be managed in the peri-operative period. It has been developed collaboratively by clinical pharmacy experts, to address the need for a national guidance for healthcare professionals.


International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer

The Lancet Oncology

In this review, the authors provide the first evidence-based international guidelines on direct oral anticoagulant use in the treatment of VTE. These guidelines
aim to address in-hospital and outpatient cancer-associated VTE in specific subgroups of patients with cancer.


Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials

The Lancet

Review of 8 RCTs (n=963) found that low-molecular-weight heparin (LMWH) does not seem to reduce risk of recurrent placenta-mediated pregnancy complications vs. no LMWH in at-risk women. However some decreases in event rates might have been too small for power of study to explore.



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:

Early real-world evidence of persistence on oral anticoagulants for stroke prevention in non-valvular atrial fibrillation: a cohort study in UK primary care


Study (n=15,242) found observed differential prescribing of oral anticoagulants (OACs) can result in channeling bias in comparative effectiveness research.
Persistence patterns changed over follow-up time, apixaban had improved persistence rates vs. other OACs.


Management and outcomes of vaginal bleeding and heavy menstrual bleeding in women of reproductive age on direct oral anti-factor Xa inhibitor therapy: a case series

The Lancet Haematology

Study (n=57, with 72 vaginal bleeding events) found vaginal bleeding, particularly heavy menstrual bleeding, is a common complication in women of reproductive age on direct oral factor Xa inhibitor therapy. Most cases can be treated conservatively.


BMJ investigation finds manufacturer failed to disclose faulty device in ROCKET AF trial of rivaroxaban

British Medical Journal

Investigation found companies were aware of concerns about faulty INRatio device, which could have put participants at unnecessary risk. It asks whether regulatory investigations could have been avoided, who was informed, FDA's concerns, and whether trial results can be trusted.


Does tranexamic acid improve outcomes in traumatic brain injury?

British Medical Journal

Review notes efficacy/safety is uncertain, although RCTs are under way. It suggests intracranial bleeding could be reduced but risk of cerebral thrombosis and
ischaemia might increase with treatment. It does not support use in routine clinical practice unless RCTs show benefit.


Novel oral anticoagulants for atrial fibrillation

British Medical Journal

Editorial notes use has proved to be highly variable in patients most at risk, (4%-70% in different areas in England), which may partly be due to clinical
uncertainty about balance of benefit to harm, and which cannot be resolved until independent scrutiny of key trial data.


New oral anticoagulants for stroke prevention in atrial fibrillation: Infographic

Pharmaceutical Journal

This infographic covers the anticoagulant effect of these agents, the slow rise of prescribing, the individual agents, and deciding which one to prescribe.


Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomised controlled trial

British Medical Journal

RCT (n=7123) found a bivalirudin monotherapy strategy vs. heparin with or without glycoprotein IIb/IIIa inhibitors, did not result in reduced major adverse
cardiovascular events or net adverse clinical events in patients with or without ST segment elevation.


Valvular heart disease and pregnancy: management of prosthetic valves


This review discusses the pregnancy risks in women with prosthetic heart valves, strategies for anticoagulation in women with mechanical heart valves, and the management of complications.



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:

New Product: Kogenate Bayer powder (human coagulation factor VIII ) and solvent for solution for injection

electronic Medicines Compendium

This product is licensed for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). This preparation does
not contain von Willebrand factor and is therefore not indicated in von Willebrand's disease.


Revised SPC: Haemoctin (Human plasma derived coagulation factor VIII)

electronic Medicines Compendium

Special warning for use in patients with existing cardiovascular risk factors has been added, which states that substitution with factor VIII may increase the
cardiovascular risk.


Edoxaban drug–drug interactions with ketoconazole, erythromycin, and cyclosporine

British Journal of Clinical Pharmacology

Report of 3 drug-drug interaction studies notes administration of dual inhibitors of P-gp and CYP3A4 increased edoxaban exposure by less than two-fold. Effect
appears to be primarily due to P- gp inhibition and impact of CYP3A4 inhibition appears to be less pronounced.


A systematic review of tranexamic acid in hip fracture surgery

British Journal of Clinical Pharmacology

Analysis of 7 studies (n=770) found moderate quality evidence that tranexamic acid reduces blood transfusion in hip fracture surgery vs. placebo (RR: 0.54; 95% CI: 0.35–0.85), with low quality evidence suggesting no increased risk of thrombotic events.


Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation


This analysis (UK) of 39,670 newly diagnosed AF patients showed that since NOACs were introduced, there has been an increase in patients receiving
guideline-recommended therapy, predominantly driven by increased use of NOACs and reduced use of other antithrombotics.



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:

Spontaneous subarachnoid haemorrhage

The Lancet

This article discusses pathophysiology, diagnosis, management, prognosis and prevention of this uncommon and severe subtype of stroke.



The Lancet

This seminar discusses the diagnosis, specific treatments for acute ischaemic and haemorrhagic stroke. It includes detail on recovery and rehabilitation, as
well as interventions under investigation and future directions.


idarucizumab (Praxbind)

Scottish Medicines Consortium

The SMC has accepted for use within NHS Scotland, idarucizumab (Praxbind®) for adults treated with dabigatran etexilate, when rapid reversal of its anticoagulanteffects is required for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding.



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:

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