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:

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

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:

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

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:

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

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:

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

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

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