Anticoagulation news items. Week commencing 26th February 2018
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.
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.
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.
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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Anticoagulation news items. Week commencing 19th February 2018
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).
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).
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.
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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Anticoagulation news items. Week commencing 5th and 12th February 2018
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.
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.
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.
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.
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%).
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.
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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Anticoagulation news items. Week commencing 29th January 2018
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.
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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Anticoagulation news items. Week commencing 22nd January 2018
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.
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.
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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Anticoagulation news items. Week commencing 15th January 2018
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.
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).
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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Anticoagulation news items. Week commencing 8th January 2018
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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Anticoagulation news items. Week commencing 2nd January 2018
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.
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%).
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.
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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Anticoagulation news items. Week commencing 18th December 2017
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.
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
Anticoagulation news items. Week commencing 11th December 2017
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).
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.
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
