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:

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

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:

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

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:

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

Characteristics of patients with atrial fibrillation prescribed antiplatelet monotherapy compared with those on anticoagulants: insights from the GARFIELD-AF registry

European Heart Journal

In GARFIELD-AF registry (n=51,270 from 35 countries), ~ half of reasons why anticoagulants are withheld in eligible patients are physicians' decisions, which range from perceived low stroke risk, risk of bleeding, falling, or fear of low compliance to guideline recommendations.

 

Revised SPCs: Advate (human coagulation factor VIII) injection- Baxject II-all presentations

electronic Medicines compendium

Scientific information on inhibitors have been updated in the SPCs.

 

Desmopressin use for minimising perioperative blood transfusion

Cochrane Database of Systematic Reviews

Review (65 RCTs; n=3874) found that differences in transfusion and blood loss when people were treated with desmopressin or placebo were small and unlikely to be of clinical importance.

 

Rituximab for treating inhibitors in people with inherited severe hemophilia

Cochrane Database of Systematic Reviews

No RCTs were identified on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The evidence base is limited to case reports and case series.

 

Topical Tranexamic Acid Compared With Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial.

Academic Emergency Medicine

RCT (N=124) reported that within 10 minutes of treatment, bleeding was stopped in 73% of the patients in the tranexamic acid group, compared with 29% in the anterior nasal packing group (difference = 44%, 95% CI, 26% to 57%; p < 0.001).

 

 

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

Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism

New England Journal of Medicine

RCT (n=1046) found edoxaban was non-inferior to dalteparin given for 6-12 months in terms of composite of recurrent VTE or major bleeding during 12 months after randomisation (12.8% for edoxaban vs 13.5% for dalteparin (HR 0.97; P=0.006 for noninferiority).

 

Meta-analysis of safety and efficacy for direct oral anticoagulation treatment of non-valvular atrial fibrillation in relation to renal function

Thrombosis Reasearch

Analysis of five RCTs comparing DOACs to warfarin in atrial fibrillation (n=72,608) found stroke risk was lower with DOACs than warfarin in both mild (RR 0.79; 95% CI 0.68–0.91) and moderate (0.80, 0.69–0.92) renal impairment, with no major differences in normal renal function.

 

Vitamin K antagonists versus low‐molecular‐weight heparin for the long term treatment of symptomatic venous thromboembolism

Cochrane Database of Systematic Reviews

There were no clear differences between low-molecular weight heparin (LMWH) and vitamin K antagonists (VKA) in preventing symptomatic VTE /death after a DVT episode. There were also no clear differences in bleeding episodes when only high-quality studies were considered.

 

 

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

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis

New England Journal of Medicine

RCT (n-692) found that between 6 and 24 months, addition of catheter-directed thrombolysis to anticoagulation did not result in lower risk of post-thrombotic syndrome (47% vs. 48%, respectively) but did result in higher risk of major bleeding. (1.7% vs. 0.3%, p= 0.049).

 

Individualised versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome (IDEAL DVT): a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial

The Lancet Haematology

This RCT (n=865) reports post-thrombotic syndrome occurred in 29% of patients receiving individualised duration of therapy and 28% of patients receiving standard duration of therapy (absolute difference was 1.1% (95% CI −5.2 to 7.3), thus meeting the non-inferiority margin.

 

Should This Patient Receive Aspirin?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center

Annals of Internal Medicine

In this discussion, experts review the 2016 US Aspirin Use for the Primary Prevention of Cardiovascular Disease.

 

Thrombo-embolic prevention after transcatheter aortic valve implantation (TAVI)

European Heart Journal

Optimal antithrombotic strategy and duration to mitigate thrombotic and bleeding risks associated with TAVI remains unclear. This review provides an overview of recent insights in this field, and highlights antithrombotic trials focusing on optimising outcomes in this setting.

 

Perioperative management of anticoagulant and antiplatelet therapy

Heart

This narrative review discusses assessment of whether interruption of anticoagulation is required, need for and management of perioperative bridging, management of patients who are receiving direct oral anticoagulants (DOACs) and management of those receiving antiplatelets.

 

 

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

Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis

British Medical Journal

Review of 23 RCTs (n=94,656) found that apixaban 5mg and dabigatran 150mg twice daily reduced the risk of stroke or systemic embolism vs warfarin. The difference vs warfarin for rivaroxaban or edoxaban was not statistically significant.

 

Dabigatran versus Warfarin for Acute Venous Thromboembolism in Elderly or Impaired Renal Function Patients: Pooled Analysis of RE-COVER and RE-COVER II

Thrombosis and Haemostasis

Pooled analysis (n=5,107) suggests that dabigatran has better efficacy than warfarin in renal impairment, probably because of an increase in the concentration of dabigatran. Incidence of major bleeding increased with increasing renal impairment for both dabigatran and warfarin.

 

FDA grant priority review for avatrombopag for thrombocytopenia in patients with chronic liver disease

Biospace Inc.

The market authorisation application in the US is based on the ADAPT 1 and ADAPT 2 phase 3 trials. Avatrombopag is a second generation orally administered thrombopoetin receptor agonist currently under investigation.

 

Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU)

British Medical Journal

RCT (n=251) does not support use of low dose aspirin (150mg daily) as adjuvant treatment for venous leg ulcers (median number of days to healing of largest ulcer: 77 for aspirin vs 69 for placebo; HR 0.85, 95% CI, 0.64 to 1.13, P=0.25).

 

 

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

Revised SPC: Xarelto (rivaroxaban) film-coated tablets (10mg, 15mg and 20mg)

electronic Medicines compendium

SPC now states when 'extended prevention of recurrent DVT and PE' is indicated (after ≥6 months therapy for DVT/PE), recommended dose is 10mg daily; 20mg should be considered in those at high risk of recurrent DVT/PE. Duration/dose should be based on benefit vs. bleeding risk.
Section 4.5 now advises that as with other anticoagulants the possibility may exist that patients are at increased risk of bleeding in case of concomitant use with SSRIs or SNRIs due to their reported effect on platelets.

 

Low-dose aspirin and risk of intracranial bleeds: An observational study in UK general practice

Neurology

Population-based cohort study of 398,158 users and non-users of prophylactic low-dose aspirin (followed over a median of 5.4 years) reports low-dose aspirin is not associated with an increased risk of any type of intracranial bleeds (1,611 cases of intracranial bleeds identified).

 

Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study

European Heart Journal

Danish cohort study (n=4541) reported that AF patients resuming oral anticoagulation following traumatic injury have lower hazard of all-cause mortality and ischaemic stroke, increased hazard of major bleeding but without additional hazards of recurrent traumatic injury.

 

Clopidogrel non-responsiveness in patients undergoing percutaneous coronary intervention using the VerifyNow test: frequency and predictors

European Journal of Hospital Pharmacy

In this Iraqi case series (n=115; mean age: 58 years; male sex: 73.9%) of whom 18.3% were clopidogrel non-responders, the major independent predictive factors for non-responsiveness were diabetes mellitus, hypertension, obesity and male sex.

 

 

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

Pulmonary embolism rule-out criteria (PERC) rule in European patients with low implicit clinical probability (PERCEPIC): a multicentre, prospective, observational study

The Lancet Haematology

Study (n=1757) found of 1052 (60%) patients with low clinical probability of PE, 49 (4.7%) had venous thromboembolism. In patients with low implicit clinical probability, 337 (32%) had negative PERC, of whom 4 (1.2%) had PE, suggesting PERC can exclude PE with few false-negatives.

 

Boehringer Ingelheim's presents subgroup analyses of RE-VERSE AD on impact of idarucizumab in patients on dabigatran with gastrointestinal bleeding or needing emergency surgery

Biospace Inc.

Of the 137 patients enrolled with a GI bleed, complete reversal of anticoagulant effect was observed in over 95% patients. Idarucizumab also rapidly and completely reversed the anticoagulant effect of dabigatran in approximately 98% patients requiring an urgent procedure.

 

Shortage of tranexamic acid tablets 500mg (all brands)

Specialist Pharmacy Service

There are limited supplies of generic tranexamic acid (TA) 500mg tablets due to difficulty sourcing raw material. Branded TA (Cyklokapron), OTC product (Cyklo-f) and some generics continue to be remain available, but there may be intermittent supplies issues until at least 2018.

 

Outcomes of Dabigatran and Warfarin for Atrial Fibrillation in Contemporary Practice: A Retrospective Cohort Study

Annals of Internal Medicine

Retrospective analysis of 50,578 started on dabigatran or warfarin showed no significant difference in rates of ischaemic stroke, or extracranial haemorrhage between the 2 groups, but those on dabigatran were less likely to have intracranial bleeding and more likely to suffer MI.

 

European CHMP issues positive opinion for paediatric license extension of Nplate (romiplostim) for chronic immune (idiopathic) thrombocytopenic purpura

European Medicines Agency

The additional indication is for patients aged one year of age and older who are refractory to other treatments (e.g. corticosteroids, immunoglobulins).

 

US FDA approves emicizumab-kxwh (Hemlibra) for prophylaxis in adult and paediatric patients with haemophilia A with inhibitors

Biospace Inc.

In the Phase III HAVEN 1 and 2 studies, prophylaxis with emicizumab was associated with a reduction in treated bleeds in adults and children with haemophilia A and factor VIII inhibitors. It will have a boxed warning regarding risk of severe blood clots.

 

 

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

An update on the bleeding risks associated with DOACs

Drug and Therapeutics Bulletin

There is uncertainty on optimal lab monitoring of anticoagulation, perioperative management and treatment of bleeding with DOACs, and currently only one licensed reversal agent in UK. Review discusses DOAC-related bleeding and role of drugs to reverse their anticoagulant action.

 

Mechanical or Biologic Prostheses for Aortic-Valve and Mitral-Valve Replacement

New England Journal of Medicine

Study (n=25,445) found mechanical (MC) mitral valves were linked to lower mortality than biologic valves in patients up to 70 years of age, whereas benefit of MC aortic valve disappeared by 55 years of age. In both cases, MC prosthesis was linked to lower risk of reoperation.

 

Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients

The Lancet
Tranexamic acid (TA) increased survival from bleeding (OR 1.20, 95% CI 1.08–1.33; p=0.001). Immediate TA improved survival by > 70% (1.72; 1.42–2.10; p<0.0001) vs later treatment. Thereafter, benefit decreased by 10% for every 15 min delay until 3 h after onset of bleeding.

 

Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years

JAMA Internal Medicine

A lower incidence of cancer associated with warfarin was noted in a Norweigian population-level study (n=1,256 725), which was reinforced by a subgroup analysis of patients with AF. Further studies are required to fully elucidate mechanisms underpinning these observations.

 

Bayer files for approval of low-dose rivaroxaban-aspirin combination therapy in EU

PharmaTimes
Bayer is seeking approval for a low-dose formulation of rivaroxaban 2.5mg administered twice daily alongside aspirin 100mg once daily for reduction of cardiovascular events in patients with coronary or peripheral artery disease. Submission is based on data from Compass study.

 

 

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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