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

Comparative table of low molecular weight heparins

Specialist Pharmacy Service

In light of current shortage of enoxaparin injection (all strengths), this table of the licensed low molecular weight heparins has been drawn up to compare/contrast key prescribing parameters.

 

Coagulopathy and haemorrhagic progression in traumatic brain injury: advances in mechanisms, diagnosis, and management

The Lancet Neurology

This Series paper explores current understanding of clinical course and underlying mechanisms of coagulopathy in traumatic brain injury. Management strategies are reviewed, including traditional use of blood products and more novel approaches, as well as thrombosis prophylaxis.

 

Idarucizumab for Dabigatran Reversal — Full Cohort Analysis

New England Journal of Medicine

Final analysis from RE-VERSE AD (n=510) reported that the primary endpoint, reversal of the anticoagulant effect of dabigatran within four hours as measured by diluted thrombin time and ecarin clotting time, was observed in 100% of patients (95% CI, 100-100).

 

Revised SPC: Xarelto (rivaroxaban) film coated tablets (all strengths)

electronic Medicines Compendium

Serious skin reactions, including Stevens-Johnson syndrome/Toxic Epidermal Necrolysis, have been reported. The highest risk appears to be early in the course of therapy. Treatment should be discontinued at the first appearance of a severe skin rash.

 

Initial anticoagulation in patients with pulmonary embolism: thrombolysis, unfractionated heparin, LMWH, fondaparinux, or DOACs?

British Journal of Clinical Pharmacology

This article gives an overview of the biophysical, pharmacokinetic and pharmacodynamic properties of anticoagulants currently available for the initial management of PE including low molecular weight heparins and direct oral anticoagulants.

 

 

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

Low-Molecular-Weight Heparin and the Relative Risk of Surgical Site Bleeding Complications: Results of a Systematic Review and Meta-Analysis of Randomized Controlled Trials of Venous Thromboprophylaxis in Patients After Total Joint Arthroplasty

Journal of Arthroplasty

Review of 45 RCTs (n= 56,730) found low-molecular-weight heparin had increased relative risk (RR) of surgical site bleeding vs. control (2.32; 95% CI, 1.40-3.85), warfarin (1.54; 1.23-1.94), and dabigatran (4.38; 1.53-12.57). There was trend towards increased risk vs. apixaban.

 

U.S. FDA grants priority review of rivaroxaban supplemental new drug application for 10 mg dose to reduce risk of recurrent venous thromboembolism (VTE)

Biospace Inc.

Application is for use of 10 mg once-daily dose to reduce risk of VTE after ≥6 months of standard anticoagulation and is based on data from EINSTEIN CHOICE study which found 2 doses of rivaroxaban (10 mg and 20 mg) to be superior to aspirin in reducing risk of recurrent VTE.

 

Risk for Major Bleeding in Patients Receiving Ticagrelor Compared with Aspirin After TIA or Acute Ischemic Stroke in the SOCRATES Study

Circulation

Review of the SOCRATES study found that bleeds occurred in 0.5% of patients on ticagrelor and 0.6% of patients on aspirin (HR 0.83 95% CI 0.52 to 1.34). Intracranial haemorrhage was reported in 0.2% of patients on ticagrelor and 0.3% on aspirin.

 

Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia: A Systematic Review

Annals of Internal Medicine

No RCTs were identified. Review of 24 observational studies (n=6153) noted no extractable data on anticoagulants, lack of uniform bleeding definitions, and systematic reporting of outcomes, thus risk–benefit ratio of antiplatelets in essential thrombocythemia is highly uncertain.

 

Conference report- Assessing the risk-benefit of anticoagulants in elderly patients with cancer-associated venous thromboembolism: a population based study

Biospace Inc.

Population-based retrospective cohort study found use of anticoagulants in patients ≥65 years with cancer-related thrombosis results in higher mortality if they develop major bleeding (MB) compared to venous thromboembolic event [VTE] (7-day mortality rate:0.5% VTE vs. 11% MB).

 

Conference report: Emicizumab showed positive results in phase III studies (HAVEN 1 and HAVEN 2) in haemophilia A with inhibitors

Biospace Inc.

HAVEN 1 showed statistically significant reduction in bleed rate of 87% (risk rate 0.13, p<0.0001) with emicizumab prophylaxis vs. on-demand treatment with bypassing agents. HAVEN 2 study noted after 12 weeks, 1 of 19 children on emicizumab reported a treated bleed.

 

FDA approves betrixiban (BevyxXa) for preventing blood clots in hospitalised patients

PharmaTimes

The US approval was based on findings of the APEX Study (n=7513), which found that betrixiban reduced incidence of DVT and PE vs enoxaparin (4.4% vs 6.0%) with no significant increase in major bleeding (0.67% vs. 0.57%).

 

 

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

Use of the Dual-Antiplatelet Therapy Score to Guide Treatment Duration After Percutaneous Coronary Intervention

Annals of Internal Medicine

Retrospective analysis of 1970 patients undergoing PCI reports prolonged dual-antiplatelet therapy (DAPT) resulted in harm in patients with low DAPT scores but reduced risk for ischaemic events in patients with high scores receiving paclitaxel-eluting stents.

 

Antithrombotic treatment after stroke due to intracerebral haemorrhage

Cochrane Database of Systematic Reviews

This review of two RCTs (n=121) concludes there is insufficient evidence to support or discourage the use of antithrombotic treatment after ICH. RCTs comparing starting vs avoiding antiplatelets /anticoagulants after ICH appear justified and are needed in clinical practice.

 

The role of contraindications in prescribing anticoagulants to patients with atrial fibrillation: a cross-sectional analysis of primary care data in the UK

British Journal of General Practice

Analysis (2004-2012) found presence/absence of recorded contraindications (CIs) has little influence on decision to prescribe anticoagulants (ACs) for prevention of stroke in AF patients. Nationally, 38,000 with AF and CIs were treated with ACs, which has safety implications.

 

It Is Time to End the Dualistic Short Versus Long Duration of Dual Antiplatelet Therapy Debates

Circulation

Viewpoint suggests it is time to end academic debate and begin clinical discussion, with a shift in focus away from dualistic short versus long duration thinking and towards discussions on which patients are best treated with short, standard or prolonged dual antiplatelet therapy.

 

Antiplatelet Therapy in Patients With Coronary Stents Undergoing Elective Noncardiac Surgery: Continue, Stop, or Something in Between?

Journal of the American Medical Association

Viewpoint notes that based on available, evidence, there is no clear link between antiplatelet strategy and rates of perioperative major adverse CV events and bleeding, even though physiological reasons would suggest that antiplatelet agents should be a factor in the risk of both.

 

Review: Indications and appropriate selection of novel oral anticoagulants in patients with atrial fibrillation

Heart

This review notes that in the absence of RCT evidence, patient-specific factors such as dosing preference (daily vs twice a day), renal function, liver function, gastrointestinal bleeding risks and drug–drug interactions can help guide treatment choice.

 

 

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

Management of superficial venous thrombosis of the leg

Drug and Therapeutics Bulletin

Review notes lack of consensus on best treatment but oral NSAIDs and compression stockings are used to provide symptomatic relief for pain and swelling. Guidelines suggest that fondaparinux or a low molecular weight heparin are options for some high risk patients.

 

Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial

The Lancet Haematology

RCT (n=100, Austria) was terminated early for futility and safety reasons because compared to patients on coagulation factor concentrates, a higher proportion of patients receiving fresh frozen plasma required rescue therapy (52 vs. 4%) and massive transfusion (30 vs. 12%).

 

Reversal strategies for non-vitamin K antagonist oral anticoagulants: a critical appraisal of available evidence and recommendations for clinical management—a joint position paper of the European Society of Cardiology Working Group

European Heart Journal

Paper notes that while available clinical data for specific antidotes of NOACs are limited, it is very likely these agents will successfully reverse.

 

Thrombophilia Testing in Provoked Venous Thromboembolism: A Teachable Moment

JAMA Internal Medicine

This Teachable Moment looks at the value of testing for inherited thrombophilia in patients with provoked venous thrombophilia.

 

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

 

The treatment of paroxysmal atrial fibrillation in UK primary care

Heart

The proportion of patients with a CHADS2 score of ≥1 prescribed anticoagulants increased between 2000 and 2015. Although improved, use in those with paroxysmal AF remains lower in 2015 (56.2% versus 69.4% in patients with persistent/permanent AF, RR 0.76; 95% CI 0.74 to 0.77).

 

Diagnosis and management of deep vein thrombosis in pregnancy

British Medical Journal

The incidence of DVT among pregnant women is around 1.1 per 1000 deliveries. This article provides an update on the diagnosis and management of pregnant women with DVT.

 

 

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

Clopidogrel reloading for patients with acute myocardial infarction already on clopidogrel therapy

European Heart Journal

This analysis of patients admitted to hospital with myocardial infarction who were on clopidogrel pre-admission (n=12,366 STEMI and 39,158 NSTEMI) found that reloading (75.8% STEMI and 25.9% NSTEMI) was not associated with increased risk of major bleeding or mortality.

 

Specific antidotes for bleeding associated with direct oral anticoagulants

British Medical Journal

This BMJ 'Practice' article discusses strategies to reverse anticoagulant activity of direct oral anticoagulants (DOACs), focusing on newer specific antidotes (idarucizumab [the only one currently licensed]; andexanet alfa, and ciraparantag).

 

 

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

Unfractionated heparin versus low molecular weight heparins for avoiding heparin‐induced thrombocytopenia in postoperative patients

Cochrane Database of Systematic Reviews

Updated review of 3RCTs (n=1398) demonstrated low-quality evidence of a lower incidence of heparin-induced thrombocytopenia (HIT), and HIT complicated by venous thromboembolism, in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH.

 

Influence of Direct Oral Anticoagulants on Rates of Oral Anticoagulation for Atrial Fibrillation

Journal of the American College of Cardiology

Study (n=655,000; CHA2DS2-VASc >1) in US found introduction of DOACs into routine practice linked to improved rates of overall oral anticoagulant use (from 52.4% to 60.7%; p<0.01; warfarin use decreased 52.4% to 34.8%; DOAC use increased 0% to 25.8%) but significant gaps remain.

 

Anticoagulation in patients with isolated distal deep vein thrombosis: a meta-analysis

Journal of Thrombosis and Haemastasis

Review of 20 studies (n= 2,936) found that anticoagulation (therapeutic or prophylactic) reduced to the risk of VTE vs no anticoagulation (OR 0.5, 95% CI 0.31-0.79). There was no significant difference in major bleeding risk (OR 0.64, 0.15-2.73).

 

FDA grant fast track designation for SB-525 gene therapy for haemophillia

PharmaTimes

SB-525 uses a recombinant adeno-associated virus (rAAV) to deliver a human Factor VIII cDNA construct. This treatment also has orphan designation in the US. EU development plans are unknown.

 

Revised SPC: Pradaxa (dabigatran etexilate) hard capsules – all strengths

electronic Medicines Compendium

The colour of Pradaxa caps have been changed according to dosage strength, as part of the worldwide harmonisation process.

 

Risk Minimisation materials for Pradaxa capsules (dabigatran etexilate): Prescriber guides for various indications and Patient Alert Card

electronic Medicines Compendium

The Prescriber guide for primary prevention of venous thromboembolic events following elective hip or knee replacement surgery provides recommendations for orthopaedic use with the aim of minimising risk of bleeding, and providing guidance on how to manage that risk.

 

Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study

European Heart Journal

RCT (n=645) reports switching dual antiplatelet therapy (DAPT) from aspirin + newer P2Y12 blocker to clopidogrel after 1 month results in occurrence of primary endpoint (composite CV death, urgent revascularisation, stroke and bleeding) of 26.3% vs 13.4% respectively (P < 0.01).

 

Educational Risk Minimisation Materials for Clexane (enoxaparin sodium)

Sanofi UK

Dear Healthcare Professional" letter notes that enoxaparin is expressed both in international units (IU) of anti-Xa activity and in milligrams (mg); and that its use in severe renal impairment is not recommended. There is also further clarification on dose regimens for DVT/PE.

 

 

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

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