European CHMP does not recommend approval of the factor Xa inhibitor betrixaban (Dexxience), intended for the prevention of venous thromboembolism

European Medicines Agency

The CHMP considered that the main study did not satisfactorily show that its benefits outweighed its risk when used for preventing blood clots in patients admitted to hospital for recent medical illness. It was approved in the US in June 2017.

 

Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism- guidance (NG89)

National Institute for Health and Care Excellence

This guideline aims to help healthcare professionals identify people most at risk and describes interventions that can be used to reduce the risk of venous thromboembolism (VTE).

 

Non-Vitamin K Antagonist Oral Anticoagulants and Risk of Serious Liver Injury

Journal of the American College of Cardiology

Analysis of Canadian administrative data (n=51,887) found current use of NOACs was not linked with increased risk of serious liver injury in patients without/with prior liver disease vs. use of vitamin K antagonists (HR:0.99;95% CI:0.68-1.45 and 0.68;0.33-1.37 respectively).

 

Association between Nonsteroidal Anti‐inflammatory Drugs and Atrial Fibrillation among a Middle‐aged Population: A Nationwide Population‐based Cohort

British Journal of Clinical Pharmacology

Taiwanese study (n= 57,058) reported that NSAID users had elevated risk of AF vs non‐users (adjusted OR=1.18, 95% CI: 1.14‐1.23). Users of non‐selective, and combined selective and non‐selective NSAIDs had elevated risk of AF (1.18; 1.13‐1.23 and 1.30; 1.21‐1.39, respectively).

 

Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation

European Heart Journal

This RCT (n=633) reports primary outcome events (bleeding, stroke, or death) were observed in 6.9% of patients on apixaban, vs 7.3% of patients on vitamin K antagonists during ablation (difference −0.4%, non-inferiority P = 0.0002 based on definition used).

 

British Society of Haematology Guideline: management of thrombotic and haemostatic issues in paediatric malignancy

British Society for Haematology

The purpose of this guideline is to provide information and guidance on the management of venous thromboembolism (VTE) and bleeding complications of cancer and its treatment especially for children with leukaemia and other forms of cancer.

 

British Society of Haematology Guidelines on the spectrum of fresh frozen plasma and cryoprecipitate products: their handling and use in various patient groups in the absence of major bleeding

British Society for Haematology

This revised guideline discusses administration of fresh frozen plasma (FFP) primarily for 3 indications: prevention of bleeding, to stop bleeding (therapeutic) or for plasma exchange, suggesting many indications in patients without major bleeding are not substantiated.

 

The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

European Heart Journal

This guide addresses management of non-vitamin K antagonist oral anticoagulants in various clinical situations eg how to deal with dosing errors, oral anticoagulant plasma level measurement (rare indications, precautions and potential pitfalls), management of bleeding etc.

 

 

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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Revised SPC: Urokinase products

electronic Medicines compendium

Diluent for further dilution, previously unspecified, is now named as sodium chloride 0.9 % solution for injection. SPC now advises that after reconstitution and further dilution in glucose 5% / 10%, urokinase solution should be used immediately, due to risk of loss in activity.

 

Effectiveness of new antiplatelets in the prevention of recurrent myocardial infarction

Heart

Real-world study (n=1047 cases;2234 controls) found recurrent MI risk is lower with ticagrelor or prasugrel vs clopidogrel;magnitude of which was larger than observed effect in trials: OR 0.65;95% CI 0.52 -0.81 and 0.71;0.53-0.96 vs 0.84 0.77-0.9 and 0.81;0.73- 0.90, respectively.

 

Imaging is the only way to diagnose blood clots in pregnancy

National Institute for Health Research Signal

An expert commentary is provided on this study which concluded biomarkers, including the D-dimer test were not useful in diagnosing PE and DVT, and imaging tests are therefore required in this population.

 

6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial

The Lancet

RCT (n=2,712) found that 6 months dual therapy was non-inferior to 12 months or longer in terms of composite risk of all cause death myocardial infarction, or stroke (absolute risk difference +0.5%, upper limit of 95% CI = 1.8% [pre-defined non-inferiority margin was 2.0%]).

 

Pharmacodynamic Effects of Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease: Results of the SWAP (Switching Antiplatelet Therapy)-4 Study

Circulation

Pharmacodynamic study (n=80) reported that de-escalation from ticagrelor to clopidogrel therapy is associated with an increase in platelet reactivity suggestive of a drug–drug interaction. A 600mg loading dose of clopidogrel is proposed except in patients who are 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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Association of Varicose Veins With Incident Venous Thromboembolism and Peripheral Artery Disease

Journal of the American Medical Association

Retrospective Taiwanese study (n=212 984 varicose veins [VVs];212 984 controls) found significantly increased risk of incident DVT among adults with VVs (6.55 vs 1.23 per 1000 person-years; HR 5.30; 95% CI, 5.05-5.56). Findings for PE and peripheral artery disease are less clear.

 

Meta-Analysis of Genotype-Guided Versus Standard Dosing of Vitamin K Antagonists

American Journal of Cardiology

Review of 20 RCTs (total n=5,980) found a greater improvement in time in therapeutic range for genotype guided vs standard treatment (difference 3.41%, p=0.01). There were also reductions in major and all bleeding events, but no difference for INR >4 or serious adverse events.

 

Oral Anticoagulation in Very Elderly Patients with Atrial Fibrillation - A Nationwide Cohort Study

Circulation

Taiwanese cohort study in those ≥90 years (11, 064 with AF vs 14,658 controls) found that warfarin was associated with a lower risk of stroke vs no treatment (3.83 vs 5.75% per year, HR 0.69, 95% CI 0.49 to 0.96). Warfarin was associated with a positive net clinical benefit.

 

Market Authorisation Application submitted in EU and USE for turoctocog alfa pegol for haemophilia

PharmaTimes

Turoctocog alfa pegol is an extended half-life factor VIII treatment currently under investigation. Data from the pathfinder clinical trial programme form the evidence base for the submission.

 

Emicizumab approved for use in EU for prevention of bleeding in haemophilia A

PharmaTimes

This bispecific monoclonal antibody simultaneously binds factor IXa & factor X, exerting the same function as factor VIII but not expected to be susceptible to neutralising antibodies. It has been approved for use on the basis of the HAVEN trial programme.

 

Anticoagulants, including non-vitamin K antagonist oral anticoagulants (NOACs): Key therapeutic topic [KTT16]

National Institute for Health and Care Excellence

This document summarises the evidence-base on anticoagulants, including non-vitamin K antagonist oral anticoagulants (NOACs). It is a key therapeutic topic which has been identified to support medicines optimisation. It is not formal NICE guidance.

 

Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves

European Heart Journal

Analysis of 137 mechanical heart valve patients reports restarting therapeutic anticoagulation (TA) within 2 weeks was associated with increased haemorrhagic complications v no-TA (26% v 6%, P < 0.01); however, a non-significant decrease in thromboembolic complications was noted.

 

Antithrombotic therapy and body mass: an expert position paper of the ESC Working Group on Thrombosis

European Heart Journal

Consensus paper addresses issue of whether modified antithrombotic management strategies are required for patients at extremes of body weight. More focus is given to obesity due to higher prevalence in cardiovascular disease and complexities with pharmacology and pathophysiology.

 

 

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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Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty

New England Journal of Medicine

RCT (n=3424 on rivaroxaban [RV] 10mg for 5 days initially) found no significant differences in symptomatic venous thromboembolism in group who continued RV or switched to aspirin (81mg daily) for additional 9 days after total knee or for 30 days after total hip arthroplasty.

 

Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging

New England Journal of Medicine

RCT terminated early for efficacy (n=182 in US) found endovascular thrombectomy plus standard medical therapy (SMT) resulted in better functional outcomes (FOs) vs. SMT alone with favorable shift in distribution of FOs on modified Rankin scale at 90 days (OR, 2.77; p<0.001).

 

A Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients with Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization

Circulation

This study in 1443 elderly ACS patients showed no difference in primary endpoint (composite of death, MI, stroke and re-hospitalisation for CV causes/bleeding within 1 year) between reduced-dose prasugrel and standard-dose clopidogrel (17% v 16.6% respectively; HR 1.007, P=0.955).

 

Antiplatelet and anticoagulant agents for secondary prevention of stroke and other thromboembolic events in people with antiphospholipid syndrome

Cochrane Database of Systematic Reviews

Review based on poor quality evidence from 5RCTs concludes that there is not enough evidence for or against NOACs or for high-intensity VKA.

 

Deep vein thrombosis

British Medical Journal
This clinical update discusses the initial approach to managing patients with suspected DVT, including presentation, diagnosis, complications and treatment (direct oral anticoagulants, low molecular weight heparin and warfarin, role of compression stockings).

 

 

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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Parenteral anticoagulation in ambulatory patients with cancer

Cochrane Database of Systematic Reviews

Review of 19 RCTs (n=9650) suggests heparin appears to have no effect on mortality at 12 and 24 months. Whilst it reduces symptomatic VTE, it likely increases major and minor bleeding. The decision for a patient with cancer to start heparin therapy should balance risks/benefits.

 

NIHR Signal: Direct acting oral anticoagulants likely to be better than warfarin for people taking them for atrial fibrillation

National Institute for Health Research Signal

An expert comment is provided of a network meta-analysis which compared 4 DOACs at various doses, warfarin and an antiplatelet agent for prevention of strokes in people with AF concluding apixaban 5mg bd was the most effective and safest intervention for several outcomes.

 

Less dementia with oral anticoagulation in atrial fibrillation

European Heart Journal

Analysis of data from Swedish Registry (n=444,106) reports anticoagulant treatment at baseline was associated with 29% lower risk of dementia than patients without anticoagulant treatment (incidence rate of dementia 1.14 vs. 1.78 per 100 patient years at risk, P < 0.001).

 

Atrial fibrillation – Updated Quality Standard [QS93]

National Institute for Health and Care Excellence

This updated quality standard has been changed to include edoxaban as an option for anticoagulation in the "rationale and definition" section; this reflects the NICE technology appraisal on edoxaban for preventing stroke and systemic embolism in people with non-valvular AF.

 

Current evidence of oral anticoagulant reversal: A systematic review

Thrombosis Reasearch

Review of 33 studies (4783 on vitamin K antagonist [VKA] and 529 on DOACs) supports use of prothrombin complex for VKA reversal. There are no studies on clinical efficacy of non-specific agents for DOAC reversal and inconsistent evidence for laboratory reversal.

 

Association of different antiplatelet therapies with mortality after primary percutaneous coronary intervention

European Journal of Heart Failure

Compared to clopidogrel (n>89,000), prasugrel was associated with lower mortality at 30 days (OR 0.87, 95% CI 0.78 to 0.97, P=0.014) and 1 year (0.89; 0.82 to 0.97, P=0.011) post PCI but ticagrelor was not.

 

NIHR Signal: Rivaroxaban plus aspirin may reduce heart attack and strokes in people with peripheral arterial disease (PAD), but with an added risk of bleeding

National Institute for Health Research Signal

Commentary notes the combination of low dose rivaroxaban plus aspirin could reduce risk of CV death, heart attack and stroke at the expense of a small increase in major bleeding in patients with stable PAD; a cost-effectiveness analysis would be helpful to determine net benefit.

 

Moving anticoagulation initiation and monitoring services into the community: evaluation of the Brighton and Hove community pharmacy service

BMC Health Services Research

The majority (98.6%) of patients attending a Community Pharmacy Anticoagulation Management Service rated it as good, very good or excellent, with 65.4% of INR readings within the target range (national target 60%) and 72.5% of time spent in therapeutic range (national target 70%).

 

Ischaemic stroke, haemorrhage, and mortality in older patients with chronic kidney disease newly started on anticoagulation for atrial fibrillation: a population based study from UK primary care

British Medical Journal

In patients aged ≥65 with chronic kidney disease, receipt of an anticoagulant within 60 days of AF diagnosis was associated with an increased risk of ischaemic stroke (HR 2.60; 95% CI 2.00 to 3.38) and haemorrhage (2.42; 1.44 to 4.05) but a lower risk of all-cause mortality.

 

Impact of anticoagulation therapy on valve haemodynamic deterioration following transcatheter aortic valve replacement

Heart

Study (n=2466) found lack of anticoagulation post-transcatheter aortic valve replacement was linked to significant increments in transvalvular gradients and greater risk of valve haemodynamic deterioration, which was not linked to major adverse clinical events in most cases.

 

 New Product: Enoxaparin BECAT pre-filled syringes with safety device

electronic Medicines compendium

This biosimilar enoxaparin is licensed for the treatment and prophylaxis of thromboembolism, for prevention of thrombus formation in extracorporeal circulation during haemodialysis, and treatment of acute coronary syndromes.

 

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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Low molecular weight heparin for prevention of venous thromboembolism in patients with lower‐limb immobilization

Cochrane Database of Systematic Reviews

Review (8 RCTs; n=3680) found moderate-quality evidence showing use of low molecular weight heparin in outpatients reduced DVT when immobilisation of lower limb was required vs. no prophylaxis/placebo. Low-quality evidence showed no clear differences in PE between groups.

 

Bypassing agent prophylaxis in people with hemophilia A or B with inhibitors

Cochrane Database of Systematic Reviews

Review of 4 RCTs (n=116) concludes prophylactic use of bypassing agents reduced bleeding events, joint bleeding events and number of affected joints. There was no evidence for improved quality of life amongst those who received prophylaxis vs those who received on-demand therapy.

 

Early use of tranexamic acid reduces bleeding more effectively

National Institute for Health Research Signal

Expert commentary is provided for a meta-analysis of 2 RCTs which found that in those with trauma bleeding or bleeding after birth, the survival benefits of tranexamic acid were estimated to decrease by 10% with every 15-minute delay in treatment.

 

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

British Journal of Clinical Pharmacology

This review discusses the potential mechanisms of action of low molecular weight heparin for the prevention of severe preeclampsia, how to optimise the selection of high-risk women for participation in future trials, and the importance of trial standardisation.

 

Randomized Comparisons of Double-Dose Clopidogrel or Adjunctive Cilostazol versus Standard Dual Anti-platelet in Patients with High Post-Treatment Platelet Reactivity: Results of the CREATIVE Trial (Clopidogrel Response Evaluation and AnTi-platelet InterV

Circulation

RCT (n=1078) found that in patients with low responsiveness to clopidogrel, as measured by thromboelastography, intensified antiplatelet strategies with adjunctive use of cilostazol improved clinical outcomes without increasing the risk of major 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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Revised SPC: Tildiem (diltiazem) – all formulations

electronic Medicines compendium

Following a recent update highlighting that diltiazem has been shown to inhibit platelet aggregation, the SPC now advises that concomitant administration with acetylsalicylates (e.g. aspirin) should be undertaken with caution.

 

Reasons for and consequences of oral anticoagulant underuse in atrial fibrillation with heart failure

Heart

Analysis of data from Swedish Heart Failure Registry noted of 21 865 patients, only 12 659 (58%) received oral anticoagulants (OACs). Reasons for not receiving OACs were not based on rational grounds and bleeding risk inappropriately affected decision-making more than stroke risk.

 

Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality

Journal of the American Medical Association

Retrospective cohort study (n=141,311 with intracerebral haemorrhage) found prior use of NOACs/warfarin was linked to higher in-hospital mortality (IHM) vs. no oral anticoagulants. Prior use of NOACs (vs. warfarin) was linked to lower risk of IHM (OR, 0.75; 97.5% CI, 0.69-0.81).

 

 

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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Risk for Arterial and Venous Thrombosis in Patients With Myeloproliferative Neoplasms: A Population-Based Cohort Study

Annals of Internal Medicine

Cohort analysis(n=45,249) reports increased incidence of arterial/venous thrombosis with HRs for arterial thrombosis at 3 months, 1 year, and 5 years of 3.0, 2.0, and 1.5, respectively and corresponding HRs for venous thrombosis of 9.7, 4.7, and 3.2 compared with matched controls.

 

Dual antiplatelet therapy: how, how long, and in which patients?

European Heart Journal

In a themed issue focusing on dual antiplatelet therapy, the 2017 European Society of Cardiology dual antiplatelet therapy guidelines are discussed and supported with case-based examples.

 

European marketing authorisation approval of rurioctocog alfa pegol (Adynovi) for haemophilia A

PharmaTimes

According to Pharmatimes, rurioctocog alfa (Adynovi) has been approved for use in Europe for on-demand and twice weekly prophylactic use in patients 12 years and older with haemophilia A.

 

Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial

The Lancet

This pre-specified subgroup analysis of the COMPASS trial (n=24,824) found rivaroxaban (2.5mg twice daily) plus aspirin (100mg daily) reduced the composite of CV death, myocardial infarction, or stroke versus aspirin alone (4% v 6%; HR 0.74, 95% CI 0.65-0.86, p<0.0001).

 

Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial

The Lancet

This pre-specified subgroup analysis of the COMPASS trial (n=7470) found rivaroxaban (2.5mg twice daily) plus aspirin (100mg daily) reduced the composite of CV death, myocardial infarction, or stroke versus aspirin alone (5% v 7%; HR 0.72, 95% CI 0.57-0.90, p=0.0047).

 

 

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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Current recommendations for anticoagulant therapy in patients with valvular heart disease and atrial fibrillation: the ACC/AHA and ESC/EACTS Guidelines in Harmony…but not Lockstep!

Heart

Based on guideline concordance and evidence, the article concludes NOACs can be used in patients with atrial fibrillation (AF) and native valve diseases (except rheumatic mitral stenosis, due to lack of data), using standard AF risk scores and AF guidelines.

 

 

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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Eltrombopag receives breakthrough designation in US for first line use in severe aplastic anaemia

Reuters Health

Eltrombopag is currently licensed in the UK for severe aplastic anaemia in patients who were either refractory to prior immunosuppressive therapy or heavily pretreated and are unsuitable for haematopoietic stem cell transplantation.

 

Telemonitoring-based feedback improves adherence to non-vitamin K antagonist oral anticoagulants intake in patients with atrial fibrillation

European Heart Journal

In small study (n=48), telemonitoring-only led to very high taking- and regimen-adherence (97.4 and 93.8% and respectively). Direct feedback further improved both to 99.0% and 96.8%. Observation without daily monitoring resulted in a significant waning of taking adherence (94.3%).

 

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

The Lancet

RCT (n=3096), which was stopped early, found 30 days of intensive antiplatelet therapy did not reduce incidence and severity of recurrent stroke or TIA in this population vs. guideline-based therapy, but did significantly increase risk of major bleeding.

 

FDA approves launch of betrixaban in US in January 2018

Biospace Inc.

Betrixaban is an oral once daily factor Xa inhibitor intended for use in patients who are at risk for thromboembolic complications due to moderate or severe restricted mobility and other risk factors for VTE. It is currently under review by the European Medicines Agency.

 

Early access to medicines scheme (EAMS) scientific opinion: emicizumab for routine prophylaxis of bleeding episodes in patients, aged 1 year and over, with haemophilia A with factor VIII inhibitors

Medicines and Healthcare products Regulatory Agency

Positive scientific opinion issued to Roche Products Limited includes a public assessment report, and treatment protocols for healthcare professionals and patients, and on the pharmacovigilance system and background information for Medical Directors.

 

Urgent reversal of vitamin K antagonists

British Medical Journal

This practice article discusses the available options for urgent reversal of the anticoagulant effects of vitamin K antagonists (prothrombinase complex concentrate; vitamin K; fresh frozen plasma), including benefits and harms, administration, monitoring and cost-effectiveness.

 

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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