Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism (Update): Draft guidance consultation

National Institute for Health and Care Excellence

A DRAFT update of NICE guideline CG92 (published January 2010), which includes new and updated recommendations on the risk assessment and prophylaxis of people at risk of venous thromboembolism, is now available for consultation.

 

Bayer halts Phase III study of rivaroxaban in embolic stroke

PharmaTimes

Bayer has halted a Phase III study investigating rivaroxaban in patients with embolic stroke of undetermined source after it showed no improvements in efficacy when compared to aspirin. Bleeding rates were low overall but higher in the rivaroxaban arm (no data presented).

 

In Use Product Safety Assessment report for Inhixa (enoxaparin biosimilar)

Specialist Pharmacy Service

This assessment, produced using the validated UKMi product assessment tool, discusses practical safety considerations associated with the introduction of this biosimilar product, including the need to ensure prescribing of product by brand name.

 

Anticoagulation combined with antiplatelet therapy in patients with left ventricular thrombus after first acute myocardial infarction

European Heart Journal

Review (n=1850 with MI) found that among those with a left ventricular thrombus given a vitamin K antagonist, those with a time in therapeutic range (TTR) ≥50% had a lower risk of thromboembolism vs those with TTR <50% (2.9% vs 19%, p=0.036) with no difference in major bleeding.

 

Indications for anticoagulant and antiplatelet combined therapy

British Medical Journal

Review notes combination treatment increases risk of bleeding, and this risk should be estimated and discussed with patients to guide treatment decisions (e.g. using risk scores such as HAS-BLED). Consideration should be given to addition of H2 antagonist or proton pump inhibitor.

 

Association Between Use of Antithrombotic Medication and Hematuria-Related Complications

Journal of the American Medical Association

Canadian retrospective cohort study (n=808,897) found that over a median follow-up of 7.3 years the rate of haematuria complications was higher in those exposed to antithrombotics vs those not exposed (123.95 vs 80.17 per 1000 person years, Rate Ratio 1.44, 95% CI 1.42-1.46).

 

Association Between Use of Non–Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation

Journal of the American Medical Association

Taiwanese study (91,330 patients on NOACs) found that those on concurrent amiodarone, fluconazole, rifampicin and phenytoin had a significant increased risk of major bleeding vs NOAC use alone (difference +13.94, +138.46 +36.90 and +52.31 incidents per 1000 person years).

 

Clinical impact of major bleeding in patients with venous thromboembolism treated with factor Xa inhibitors or vitamin K antagonists

Thrombosis and Haemostasis

Combined data from the EINSTEIN, AMPLIFY and HOKUSAI-VTE studies found that factor Xa inhibitor associated major bleeding events in these studies had a less severe presentation and similar course compared to vitamin K antagonists.

 

Shortage of abciximab (Reopro) 2mg/ml solution for injection or infusion

Specialist Pharmacy Service

There is a potential 6 month supply issue affecting abciximab from October through till March 2018. This memo advises on alternative treatment options in the interim should stock run out.

 

Low-Dose vs Standard-Dose Alteplase for Patients With Acute Ischemic Stroke: Secondary Analysis of the ENCHANTED Randomized Clinical Trial

JAMA Internal Medicine

This secondary analysis of a RCT that involved 3310 patients with acute ischaemic stroke found no clear differential benefits of low-dose alteplase compared with standard-dose alteplase in disability outcomes, irrespective of age, race/ethnicity, and neurological severity.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

Miconazole (Daktarin): over-the-counter oral gel contraindicated in patients taking warfarin

Medicines and Healthcare products Regulatory Agency

Patients taking warfarin should not use over-the-counter miconazole oral gel. If concomitant use is planned via prescription, the anticoagulant effect of warfarin should be monitored carefully. Patients who experience signs of bleeding should seek immediate medical attention.

 

Meta-Analysis of Safety and Efficacy of Uninterrupted Non–Vitamin K Antagonist Oral Anticoagulants Versus Vitamin K Antagonists for Catheter Ablation of Atrial Fibrillation

American Journal of Cardiology

Review of 13 studies (3 RCTs and 10 observational studies, total n=4,878) found no significant difference in the risk of major bleeding, systemic thromboembolism and symptomatic stroke/TIA, though the evidence was not of high quality.

 

Evolving landscape of stroke prevention in atrial fibrillation within the UK between 2012 and 2016: a cross-sectional analysis study using CPRD

BMJ Open

Cohort study showed an increasing proportions of patients with non-valvular AF receiving anticoagulant therapy (16.7% rise), together with similar reductions in antiplatelet (16.8% decrease). The proportion of patients not receiving antithrombotics remained the same (15%).

 

Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial

Journal of the American Medical Association

RCT (n=1,650) found that fewer patients in the geno-type guided group had a composite outcome event (major bleeding, INR>4, VTE or death) vs clinically guided warfarin (10.8% vs 14.7%, RR 0.73, 95% 0.56 to 0.95).

 

Phase III L-PLUS2 study investigating lusutrombopag for the treatment of thrombocytopenia in patient with chronic liver disease undergoing elective invasive procedures meets primary endpoint

Biospace Inc.

This study (n=215) reports that more patients on lusutrombopag vs placebo (64.8% vs 29.0%) met the primary efficacy endpoint (defined as proportion of patients who required no platelet transfusion prior to the invasive procedure) and no rescue therapy for bleeding post procedure.

 

Interhospital Transfer Prior to Thrombectomy is Associated with Delayed Treatment and Worse Outcome in the STRATIS Registry

Circulation

Median onset-to-revascularisation time was 202 minutes for direct presentation vs 311 minutes for interhospital transfer in 984 patients undergoing mechanical thrombectomy for severe stroke (p<0.001). Mortality did not differ and IV alteplase did not impact outcomes.

 

New Drug Application submission to FDA for avatrombopag, an oral second generation thrombopoietin receptor agonist

Biospace Inc.

The NDA was based on data from two Phase III trials, ADAPT-1 and ADAPT-2, that evaluated the efficacy and safety of avatrombopag for the treatment of severe thrombocytopenia (<50,000/μL) in patients with chronic liver disease who are scheduled to undergo a procedure.

 

Diagnosis and management of postpartum haemorrhage

British Medical Journal

Review notes this is second leading direct cause of maternal deaths in UK. It recommends tranexamic acid for all women with atonic and traumatic postpartum haemorrhage as well as for ongoing haemorrhage during a caesarean section.

 

National community pharmacy oral anticoagulant safety audit

Specialist Pharmacy Service

This audit will provide insight on patient awareness of key information about their anticoagulant, use of alert cards and compliance with monitoring requirements. Results will be used to inform a national update of patient held oral anticoagulant information and alert cards.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

Screening for Occult Cancer in Patients With Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis of Individual Patient Data

Annals of Internal Medicine

10 studies (n=2,316) found a 12 month prevalence of cancer after VTE of 5.2%. The point prevalence of cancer was higher in those with extensive screening vs limited screening initially (OR 2.0, 95% CI 1.2 to 3.4), but not at 12 months (OR 1.4, 95% CI 0.89 to 2.1).

 

Effects of Anticoagulants in Patients With Cirrhosis and Portal Vein Thrombosis: A Systematic Review and Meta-analysis

Gastroenterology

Review of 8 studies (n=353) found that more patients given anticoagulants underwent portal vein thrombosis recanalization vs no treatment (71% vs 42%, p<0.0001). There was no difference in major or minor bleeding in the 6 studies that reported this.

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

Bleeding-related hospital admissions and 30-day readmissions in patients with non-valvular atrial fibrillation treated with dabigatran versus warfarin

Journal of Thrombosis and Haemastasis

Dabigatran vs warfarin, was associated with comparable incidence of first hospital admission (incidence rate ratio, 0.92; 95% CI, 0.66-1.28) but higher risk of 30-day readmission with respect to bleeding (adjusted HR, 2.87; 95%CI, 1.10-7.43) in 51,946 Hong Kong patients with AF.

 

The management of antiplatelet therapy in acute coronary syndrome patients with thrombocytopenia: a clinical conundrum

European Heart Journal

In the absence of clinical guidance, this review discusses the evidence and proposes management strategies for antiplatelet therapy in patients with acute coronary syndrome and thrombocytopenia.

 

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation–Related Mild Ischemic Stroke A Randomized Clinical Trial

JAMA Neurology

This RCT (n=195) reports in patients with mild acute ischaemic stroke and AF, new ischaemic lesions or intracranial haemorrhage (noted on MRI imaging) after 4 weeks occurred in 49.5% of patients receiving rivaroxaban v 54.5% receiving warfarin (nonsignificant difference, p=0.49).

 

Long-term mortality and prehospital tirofiban treatment in patients with ST elevation myocardial infarction

Heart
Subgroup analysis of the On-TIME 2 trial (n=984) found that baseline N-terminal pro-B-type natriuretic peptide level predicted long-term mortality. In those with high levels, early prehospital treatment with tirofiban significantly reduced 30-day and 1-year mortality vs placebo.

 

Factor VIII medicines: no clear and consistent evidence of difference in risk of inhibitor development between classes

European Medicines Agency

The European Medicines Agency has concluded there is no clear evidence of a difference in risk of inhibitor development between recombinant factor VIII medicines and those derived from plasma. The risk of inhibitor development should be evaluated individually for each medicine.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

 

 

 

Pharmacovigilance Risk Assessment Committee (PRAC) confirms its previous conclusion on risk of inhibitor development with factor VIII medicines

European Medicines Agency

The PRAC has confirmed its previous conclusion that there is no clear and consistent evidence of a difference in the incidence of inhibitor development between the two classes of factor VIII medicines: plasma-derived and made with recombinant DNA technology.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial

The Lancet

Guided de-escalation of antiplatelet therapy (one week prasugrel then one week clopidogrel, followed by maintenance treatment dictated by platelet function testing) was non-inferior to 12 months prasugrel for net clinical benefit at one year (7% v 9%; HR 0.81; 95% CI 0.62-1.06]).

 

Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation

New England Journal of Medicine

In patients with AF who had undergone PCI (n= 2725), dabigatran (110 mg or 150 mg bd) plus P2Y12 inhibitor (clopidogrel or ticagrelor) resulted in risk of major or clinically relevant non-major bleeding events that was significantly lower than risk with warfarin triple therapy.

 

Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease

New England Journal of Medicine

In patients with stable atherosclerotic vascular disease (n=27,395), rivaroxaban (2.5 mg bd) plus aspirin led to better CV outcomes but more major bleeding events vs aspirin. Rivaroxaban (5 mg bd) did not result in better CV outcomes vs aspirin and more major bleeding events.

 

A multifaceted intervention to improve treatment with oral anticoagulants in atrial fibrillation (IMPACT-AF): an international, cluster-randomised trial

The Lancet

Educational intervention (providers and patients, with regular monitoring and feedback), aimed to improve use of oral anticoagulation in patients with AF, resulted in an increase in patients treated with oral anticoagulants (68% to 80%) vs usual care (64% to 67%).

 

Bivalirudin versus Heparin Monotherapy in Myocardial Infarction

New England Journal of Medicine

This Swedish registry-based study (n=6006) reports among patients undergoing PCI for MI, the rate of the composite of death from any cause, MI, or major bleeding was similar among those who received bivalirudin vs heparin monotherapy (12.3% vs 12.8%, HR 0.96; 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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

 

FDA grants priority review to licensing application for haemophilia drug emicizumab

Reuters Health

Roche said submission is based on positive data from phase 3 study in adolescents/adults with haemophilia A with inhibitors (IHs) and interim phase III results in children. It said ~30% patients develop IHs limiting treatment options and increasing risk of life-threatening bleeds.

 

NIHR Signal: Drug reduces deaths from bleeding after childbirth

National Institute for Health Research Signal

Expert commentary is provided for an RCT (20,600 women with post-partum haemorrhage) which found that IV tranexamic acid reduced the risk of death from bleeding vs placebo. The challenge is to promptly implement the early use of tranexamic acid into best practice.

 

Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets. S2TOP-BLEED

Neurology

A prediction model for major bleeding in patients with a TIA or ischaemic stroke on antiplatelets was developed following review of data from 6 RCTs. Authors claim that the S2TOP-BLEED score had a reasonable external validation but slightly underestimated the major bleeding risk.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

Resubmission of licence application for andexanet alfa accepted by the FDA

Biospace Inc.

The resubmission contains supplementary information that had been requested by the FDA. Andexanet alfa is a factor Xa inhibitor reversal agent. In December 2016, following a market authorisation application. In the EU additional data from the manufacturers had also been requested.

 

Update on antithrombotic therapy after percutaneous coronary revascularisation

The Lancet

This article, the third in a Series of three about percutaneous coronary intervention, provides an update on antithrombotic therapy after percutaneous coronary revascularisation, discussing current available evidence and how to integrate these findings into clinical decisions.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

Disease understanding in patients newly diagnosed with atrial fibrillation

Heart

Survey analysis (1,004 responses) found that about half of patients with new-onset atrial fibrillation understood the benefits of anticoagulation at the time of diagnosis and understanding improved over the first 6 months. Authors suggest a need for more ongoing patient education.

 

New product: Inhixa (enoxaparin biosimilar) solution for injection in prefilled syringe

electronic Medicines compendium

Inhixa (first enoxaparin biosimilar launched in the UK) is licensed for the same indications as Clexane® and is available in the following strengths: 2,000 IU (20mg) in 0.2mL, 4,000 IU (40mg) in 0.4mL, 6,000 IU (60mg) in 0.6mL, 8,000 IU (80mg) in 0.8mL, 10,000 IU (100mg) in 1mL.

 

Impact of design of coronary stents and length of dual antiplatelet therapies on ischaemic and bleeding events: a network meta-analysis of 64 randomized controlled trials and 102 735 patients

European Heart Journal

Rates of major adverse CV events were similar in all treatment arms, but some secondary outcomes varied by stent type. Prolonged dual antiplatelet therapy was linked to lower MI incidence in patients with an everolimus/zotarolimus-eluting stent but a higher bleeding rate.

 

 

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:

 

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

 

Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial

The Lancet Neurology

In patients with acute stroke, achievement of an excellent functional outcome (modified Rankin Scale score 0–1) at 3 months was similar for tenecteplase (64%) and alteplase (63%). Further trials are needed to establish whether tenecteplase is non-inferior to alteplase.

 

Non-vitamin-K antagonist oral anticoagulants (NOACs) for the prevention of stroke and systemic embolism in people with atrial fibrillation: commissioning support

Midlands Therapeutics Review and Advisory Committee

Commissioners should ensure robust processes/local initiatives are in place to identify patients with AF at increased risk of stroke, and a record made of decision whether or not to proceed with treatment. They should refer to NICE CG 180 and range of decision support tools.

 

Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study

European Heart Journal

In trial of 422 DOAC-treated patients requiring invasive procedure, last dose of DOAC 3 days before procedure resulted in minimal pre-procedural anticoagulant effect for almost all patients. Moderate renal impairment and antiarrhythmics should result in longer DOAC interruption.

 

Drug Trial Snapshots: Bevyxxa (betrixaban)

US Food and Drug Administration

This Drug Trials Snapshot is intended as a tool for consumers to use when discussing risks/benefits of betrixaban for the prevention of venous thromboembolism (VTE) in hospitalised adults at risk for developing VTE. The FDA approval was based on evidence from one clinical trial.

 

Mechanical versus bioprosthetic aortic valve replacement

European Heart Journal

Review notes main reason to opt for bioprosthesis is to avoid lifelong anticoagulation (AC) which has resulted in increase in use of bioprosthetic as opposed to mechanical valves. Currently, there is not enough evidence to support routine AC after bioprosthetic valve implantation.

 

Direct Healthcare Professional Communication: Clexane (enoxaparin sodium): Updates to strength expression, dose regimens in DVT/PE, use in patients with severe renal impairment

Sanofi UK

Product information has been harmonised in EU. Strength will now be expressed both in IU of anti-Xa activity and in mg. Treatment dose for DVT/PE has been clarified. Use in end stage renal disease (creatinine clearance <15 ml/min) is not recommended outside haemodialysis setting.

 

Shortage of enoxaparin injection: alternative treatment options

Specialist Pharmacy Service

In light of current shortage of enoxaparin injection (all strengths), a table of licensed low molecular weight heparins has been drawn up to compare/contrast key prescribing parameters and a section on DOACs included to highlight where they could be used in certain settings.

 

Antiphospholipid syndrome and pregnancy: Pathogenesis to translation

Arthritis & Rheumatology

Antiphospholipid syndrome (APS) is an autoimmune condition linked with thrombosis and adverse pregnancy outcomes. Review discusses abnormal placental development, prediction of adverse pregnancy outcomes in APS and SLE, and potential targets to prevent obstetric APS.

 

Subarachnoid Hemorrhage

New England Journal of Medicine

Subarachnoid hemorrhage without preceding trauma is caused by rupture of an intracranial aneurysm in 80% of cases. This review discusses signs /symptoms, evaluation, medical interventions to reduce risk of rupture, treatment of ruptured cerebral aneurysms and of complications.

 

Duration of Dual Antiplatelet Therapy in Patients with an Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

American Journal of Medicine

Meta-analysis of 8 trials (n=12,917) found no significant difference in CV mortality/MI/major bleeding between shortterm and 12-month/extended dual antiplatelet therapy (eDAPT).However, 12-month DAPT showed significantly higher risk of MI but reduced major bleeding risk vs. eDAPT.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

Page 1 of 19