Anticoagulation news items. Week commencing 1st and 8th December 2014
Circulation
This study noted that bridging anticoagulation is used in a-quarter of anticoagulation interruptions and is linked to higher risk for bleeding (5.0 vs. 1.3%, OR 3.84, p<0.0001) and adverse events (13 vs. 6.3%; OR 1.94, p=0.0001) vs. non-bridging.
Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis
New England Journal of Medicine
RCT in 300 patients found FXI-ASO was non-inferior (200mg OD) or superior (300mg OD) to enoxaparin 40mg OD daily in prevention of VTE in patients undergoing total knee arthroplasty (VTE in 27%, 4% and 30%; and bleeding in 3%, 3%, and 8%; respectively).
Biospace Inc.
Administration of idarucizumab in these groups (n=46) resulted in immediate, complete and sustained reversal of the anticoagulation effects of dabigatran. Anticoagulation was restored when volunteers were re-dosed with dabigatran 24 hours after idarucizumab was administered.
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 24th November 2014
Meta-analysis on Risk of Bleeding with Apixaban in Patients with Renal Impairment
American Journal of Cardiology
In 6 trials (n= 40,145), risk of bleeding with apixaban in patients with mild renal impairment (RI) was significantly less (RR, 0.80; 95% CI, 0.66 to 0.96) vs. conventional anticoagulants, but was similar in patients with moderate-severe RI (1.01; 0.49 to 2.10).
Warfarin Versus Novel Oral Anticoagulants: How to Choose?
Circulation
This article for patient describes the differences between NOACs and warfarin, use of NOACs for mechanical heart valves and how to select an agent.
Stroke
This exploratory analysis of RCT (n=3035) examining whether long-term survival varied by baseline characteristics after alteplase treatment supports improving acute stroke patients' access to earlier (<3 vs. 3–6 hours) alteplase treatment and treating those with poor prognosis.
The Lancet Neurology
This pathway provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation, leading to an increase in use of thrombolysis and an improvement in clinical outcome, although mortality did not change.
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 17th November 2014
CHMP issues positive opinion on licensing of vorapaxar (Zontivity) in EU
European Medicines Agency
Vorapaxar 2mg film tablet is intended for the reduction of atherothrombotic events in adult patients with a history of MI and should be co-administered with aspirin, and where appropriate, with clopidogrel.
Journal of the American College of Cardiology
This RCT, terminated early due to recruitment problems (n=2031 of planned 2475) found rates of bleeding and of thrombotic events were not significantly different for 6- vs. 24-month dual antiplatelet therapy after PCI with new-generation DES in aspirin responders.
Journal of the American Medical Association
This study found mechanical left atrial appendage closure to be non-inferior and superior to warfarin in patients with nonvalvular AF and CHADS2 score ≥1 in preventing the combined outcome of stroke, systemic embolism and CV death (rate of 2.3 v 3.8 events per 100 patient-years).
Interim data on dabigatran versus warfarin for AF in routine care
Biospace Inc.
An interim analysis of two health insurance databases show that patients with non-valvular AF treated with dabigatran had a lower rate of major haemorrhage (354 v 395 events; HR 0.75) and stroke (62 v 69; HR 0.77, not statistically significant) vs. those receiving warfarin.
Ponatinib (Iclusig▼): risk of vascular occlusive events
Medicines and Healthcare products Regulatory Agency
An EU review on the risk of serious vascular occlusive events with ponatinib has been completed. The available evidence shows that the risk is likely to be dose-dependent; however the data are insufficient to recommend reducing the ponatinib dose.
Annals of Internal Medicine
In patients with AF receiving anticoagulants, exposure to NSAIDs increased the risk of serious bleeding (additional 1.9 events per 1000 patients). The majority of events (38.7%) were gastrointestinal; 18.9% were intracranial. Thromboembolism risk was also increased.
Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate
Circulation
In this randomised, placebo-controlled Phase 1 study (n=110), a 4-factor prothrombin complex concentrate reversed the effects of edoxaban on bleeding duration following punch biopsy in a dose-dependent manner, with complete reversal observed following 50 IU/kg.
JAMA Neurology
The availability of a stroke emergency mobile unit increased rates of thrombolysis overall (32.6% v 22% with conventional care; P<0.001) and the rates delivered within the first 'golden hour' after symptom onset (31.0% v 4.9%; P<0.01). Short-term mortality rates were similar.
Controversies in cardiovascular medicine – pre-treatment with P2Y12 inhibitors in NSTEMI
Circulation
Two linked articles discuss whether pre-treatment with P2Y12 inhibitors in Non–ST-segment–elevation acute coronary syndrome is clinically justified.
Extended duration dual antiplatelet therapy and mortality: a systematic review and meta-analysis
The Lancet
This analysis of 14 trials that randomised participants to different durations of dual antiplatelet therapy (DAPT) did not find any difference in all-cause, cardiovascular (CV) or non-CV mortality between extended duration and short-duration DAPT (≤6 months) or aspirin alone.
Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents
New England Journal of Medicine
Patients with a drug-eluting stent who continued dual antiplatelet therapy >1 year had a lower risk of stent thrombosis and major adverse cardiovascular and cerebrovascular events, but increased all-cause mortality (secondary endpoint; HR 1.36; 95% CI, 1.00 to 1.85; P=0.05).
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 10th November 2014
Development of investigational antibody MEDI2452 for reversal of antiplatelet effects of ticagrelor
Biospace Inc.
A pre-clinical development program is evaluating the ability of MEDI2452 to rapidly and specifically reverse the antiplatelet effects of ticagrelor in emergency situations that cause major bleeding, such as surgery.
British Medical Journal
In patients with STEMI undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor (GPI) and LMWH plus GPI were most efficacious in terms of avoiding major adverse cardiovascular events in the short-term; bivalirudin was associated with the lowest bleeding risk.
Platelet Transfusion: A Clinical Practice Guideline From the AABB
Annals of Internal Medicine
These US guidelines provide pragmatic recommendations on the appropriate use of platelet transfusion (prophylactic and therapeutic) in adults, based on the best available published evidence.
Vitamin K for Patients with High International Normalized Ratios (INRs): Safety
Canadian Agency for Drugs and Technologies in Health
A limited literature search identified one non-randomised study which found that withholding warfarin or giving vitamin K treatment to patients on oral anticoagulants who have an INR >9 did not effectively reduce the INR within 24 hours.
European Medicines Agency
The PRAC is recommending further examination of the available evidence for Kogenate Bayer/Helixate NexGen, as new evidence has shown it may be associated with a higher risk of inhibitor (antibody) development than other FVIII products in treatment-naïve haemophilia patients.
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 3rd November 2014
Use of PER977 to Reverse the Anticoagulant Effect of Edoxaban
New England Journal of Medicine
In double-blind, placebo-controlled dose escalation trial in 80 healthy people given 60mg edoxaban, baseline haemostasis was restored from anticoagulated state in 10-30 minutes after administration of 100-300 mg of PER977 and was sustained for 24 hours. Phase 2 studies underway.
NHS Improving Quality
53.6% suitable patients (pts) in England are on anticoagulants. If warfarin prescribed for all of above with CHA2DS2-VASc ≥2, further 11,600 AF-related CVAs would be averted/year, with additional 1500 excess bleeds, and decrease in number of deaths in AF pts over 1-year by 3500.
JAMA Internal Medicine
The authors of this viewpoint article discuss the risks and benefits of vorapaxar and conclude that although it has a potential role in the secondary prevention of cardiovascular disease, they remain sceptical of its widespread use as part of a 3-drug antiplatelet regimen.
National Institute for Health and Care Excellence
A systematic review and meta-analysis of observational studies found that there was a statistically significantly increased risk of venous thromboembolism (VTE) among users of NSAIDs compared to non-users of NSAIDs. However, the meta-analysis has a number of important limitations.
European Heart Journal
This study reports a relatively low risk of VTE beyond 3 months after radiofrequency ablation for AF. The authors suggest the risk of bleeding with oral anticoagulation may outweigh benefits in this setting, but randomised studies are required to confirm their findings.
Risk of Bleeding With Dabigatran in Atrial Fibrillation
JAMA Internal Medicine
This analysis of Medicare patients who started warfarin (n=8102) or dabigatran (n=1302) within 60 days of AF diagnosis reports that dabigatran was associated with a higher risk of overall, major and GI bleeding (HR 1.30, 1.58 and 1.85 v warfarin) but lower risk of ICH (HR 0.32).
Biospace Inc.
The EMA has validated an application seeking approval of Elocta™, a recombinant factor VIII Fc fusion protein product candidate for the treatment of haemophilia A. The application includes results from the A-LONG and Kids A-LONG Phase III studies.
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 27th October 2014
Circulation
Retrospective cohort study in general practice found dabigatran linked to reduced risk of ischaemic stroke, intracranial bleed, and death, and increased risk of major GI bleed vs. warfarin in elderly patients with non-valvular AF. These links more pronounced with 150mg BD dose.
The Lancet Neurology
RCT (n=2876) found despite previously reported decrease proximal DVT risk at 30 days (primary endpoint), there were no significant differences in disability, living circumstances, or health-related QoL in patients using or not using intermittent pneumatic compression.
National Institute for Health and Care Excellence
DRAFT guidance recommends dabigatran etexilate, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults.
UKMi
This document highlights key factors influencing anticoagulant choice, identification of patients taking anticoagulants, when might warfarin be the preferred option, and active swapping from warfarin to novel agents.
FDA advisory panel recommends approval of edoxaban 60mg in selected AF patients
Reuters
Advisory panel to FDA has recommended approval of 60 mg dose of edoxaban, a once-daily anticoagulant that inhibits Factor Xa, for use in patients with AF, but only in those with mild renal impairment, as outcomes vs. warfarin were worse in those with normal renal function.
US Food and Drug Administration
The US FDA has approved Obizur (Antihaemophilic Factor (Recombinant), Porcine Sequence) for the treatment of bleeding episodes in adults with acquired haemophilia A.
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 20th October 2014
Acute coronary syndrome - rivaroxaban [ID532]: consultation document
National Institute for Health and Care Excellence
DRAFT guidance recommends rivaroxaban as option, in combination with aspirin plus clopidogrel/aspirin alone, for preventing atherothrombotic events in people who have had an ACS with elevated cardiac biomarkers. Risk of bleeding should be assessed before treatment is started.
Heart
In patients with STEMI treated with primary PCI, chronic use of vitamin K antagonist (VKA) was associated with an increased risk of in-hospital major bleed (17.0% v 10.1% in those not on VKA). In those on VKA, glycoprotein inhibitors were associated with increased bleeding risk.
New product: Nuwiq (human coagulation factor VIII, simoctocog alfa)
electronic Medicines Compendium
Nuwiq is licensed for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). Dose and duration depend on the severity of the factor VIII deficiency, location and extent of the bleeding and the patient's clinical condition.
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 13th October 2014
New product: Xarelto (rivaroxaban) 2.5 mg film-coated tablets
electronic Medicines Compendium
Rivaroxaban co-administered with aspirin alone or with aspirin plus clopidogrel or ticlopidine, is indicated for prevention of atherothrombotic events in adult patients after an ACS with elevated cardiac biomarkers.
Guideline for the diagnosis and management of the rare coagulation disorders
British Journal of Haematology
This guideline covers the diagnosis and management of patients with rare coagulation disorders, defined as monogenic bleeding disorders caused by deficiency of a soluble coagulation factor or factors, other than von Willebrand disease, Haemophilia A or Haemophilia B.
dabigatran etexilate (Pradaxa)
Scottish Medicines Consortium
The SMC has accepted dabigatran etexilate (Pradaxa®) for use within NHS Scotland for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. Cost-effectiveness of longer-term use (>18 months) is uncertain.
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 6th October 2014
Anticoagulation in adults with congenital heart disease: The who, the when and the how?
Heart
This article reviews the current use of anticoagulation in patients with congenital heart disease. It discusses treatment and monitoring with warfarin, heparin and the new oral anticoagulants, and who and when to treat.
National Institute for Health and Care Excellence
A randomised controlled trial reported that continuing dual antiplatelet therapy beyond a year after stent implantation did not statistically significantly reduce the risk of the combined outcome of death or cardiovascular events compared with continuing aspirin monotherapy....
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 September 2014
JAMA Internal Medicine
The authors of this research letter report that women, elderly patients, and those of non-white racial backgrounds are underrepresented in the RCTs of US (ACC/AHA) guidelines for AF, HF, and ACS, raising concerns about their applicability in these populations.
Journal of Clinical Oncology
The results of this study suggest that in patients with cancer treated with LMWH for 6 months for a first DVT, continuation for a further 6 months in those with residual vein thrombosis did not reduce the rate of recurrent VTE. Those without RVT at 6 months are a low risk group.
JAMA Internal Medicine
This meta-analysis of observational studies suggests that women with STEMI treated with primary PCI have a higher risk of in-hospital mortality than men; this association is likely however to be confounded by baseline CV risk factors and differences in clinical profile.
Ministry of Health, Labour and Welfare in Japan approves edoxaban for additional indications
Biospace Inc.
The oral factor Xa inhibitor edoxaban has been approved in Japan for the prevention of ischaemic stroke and systemic embolism in patients with non-valvular AF and for treatment and secondary prevention of VTE. It is currently under regulatory review in the EU for these indications.
Canadian Agency for Drugs and Technologies in Health
This article reviews current evidence of comparative efficacy and safety of monotherapy or combination medical interventions for patients with chronic thromboembolic pulmonary hypertension. Studies of riociguat, bosentan and sildenafil are summarised.
Non-adherence to cardiovascular medications
European Heart Journal
The authors of this review on non-adherence to cardiovascular medications, which is increasingly recognised, conclude that in the face of a rapidly expanding population at risk for CHD, effective means of ensuring patient adherence to evidence-based therapy are urgently needed.
All Wales Advice on the Role of Oral Anticoagulants
All Wales Medicines Strategy Group
This updated document covers the safe and effective use of oral anticoagulants for the prevention of stroke and systemic embolism in people with non-valvular AF. It considers assessment, drug choice, review, prescribing responsibility, and INR monitoring for warfarin.
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
