Anticoagulation news items. Week commencing 29th June 2015
New product: Edoxaban (Lixiana) 60mg Film-Coated Tablets
electronic Medicines Compendium
Licensed for prevention of stroke and systemic embolism in adults with non valvular AF with 1 or more risk factors such as CHF, HBP, age ≥ 75 years, DM, prior stroke or TIA, prevention of recurrent DVT/PE, and treatment of DVT/PE.
Revised SPC: Rivaroxaban (Xarelto) 10 and 20mg tablets
electronic Medicines Compendium
Advice on how to reduce the potential bleeding risk associated with concurrent use of rivaroxaban and neuraxial (epidural/spinal) anaesthesia or spinal puncture have been added. The following AEs are now listed: cholestasis, hepatitis and thrombocytopenia.
British Journal of General Practice
This UK cohort study of 296 adults self-monitoring their oral anticoagulation therapy (median 61 years; predominately professional or held a university qualification) found 90.2% were still self-monitoring after 12 months, with a mean time in therapeutic range of 75.3%.
Annals of Internal Medicine
This tool advocates regular, standardised clinical monitoring of patients receiving novel oral anticoagulants. It consists of a checklist covering adherence assessment and counselling, bleeding risk assessment, creatinine clearance, drug interactions and examination (e.g. BP).
Stroke
This analysis of the Swedish stroke register found the prescribing of anticoagulants after stroke in patients with AF varied according to age, income, education and country of birth. This was not explained by common risk factors suggesting socioeconomic inequalities.
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 22nd June 2015
High-dose ibuprofen (≥2400mg/day): small increase in cardiovascular risk
Medicines and Healthcare products Regulatory Agency
EU review confirms that CV risk of high-dose ibuprofen (≥2400mg/day) is similar to COX 2 inhibitors and diclofenac. Clinicians are advised that naproxen and low-dose ibuprofen (≤1200mg per day) are considered to have most favourable thrombotic CV safety profiles of all NSAIDs.
American Journal of Cardiology
Review of 4 RCTs (n=31,470 with NSTE-ACS) found newer oral P2Y12 inhibitors decrease major cardiovascular events (MACEs) and MI at expense of significant increase in bleeding risk. Treatment of 1000 patients will prevent 16 MACEs at expense of increase in 6 major bleeds.
BMJ Open
Review of 26 RCTs (n=8763) suggests self-monitoring (SM) appears to be a safe and cost-effective option. It found that both SM and self-testing were as safe as standard care (SC) in terms of major bleeding events. SM was also linked to fewer thromboembolic events vs. SC.
Circulation
Of 1776 Japanese patients who presented with de novo AMI between 2001 and 2013, prevalence of coronary artery embolism (CE) was 2.9% (n=52). AF was the most common cause (n=38, 73%). Only 39% of patients with CE were treated with vitamin K antagonists, and median INR was 1.42.
Association of Rivaroxaban Anticoagulation and Spontaneous Vitreous Hemorrhage
JAMA Opthalmology
This report describes 3 patients who developed spontaneous vitreous haemorrhage after initiating rivaroxaban. All 3 patients were taking an additional antithrombotic agent (2 warfarin, 1 clopidogrel) at the time of haemorrhage.
European Medicines Agency
The licence extension will be for prophylaxis and treatment of haemorrhage or surgical bleeding in patients with von Willebrand Disease, when desmopressin treatment alone is ineffective or contraindicated.
Revised SPC: Konakion (phytomenadione) MM (10mg/ml and Paediatric 2 mg/0.2 ml)
electronic Medicines Compendium
SPC notes reports of anaphylactoid reactions after IV injection. Local irritation may occur at injection site but is unlikely due to the small injection volume. Rarely, injection site reactions may occur which may be severe, including inflammation, atrophy and necrosis.
Circulation
Analysis (n=18,201 of which 4808 had valvular heart disease [VHD]) or prior valve surgery found no evidence of differential effect of apixaban over warfarin in patients with and without VHD in reducing stroke and systemic embolis, causing less bleeding, and reducing death.
Characterising and predicting bleeding in high-risk patients with an acute coronary syndrome
Heart
Analysis of APPRAISE-2 study (n=7392) found that when compared with placebo, use of apixaban is linked to an important short-term and long-term risk of bleeding in high-risk post-ACS patients, with GI bleeding being most common source of major bleeding.
Superficial thrombophlebitis (superficial venous thrombosis)
British Medical Journal
This reviews covers epidemiology, diagnosis, causes, types of superficial thrombophlebitis, complications, investigations, treatment (hosiery, NSAIDs, anticoagulation, antibiotics, surgery), and when to refer.
PharmaTimes
Edoxaban is a once-daily selective factor Xa-inhibitor which has been licensed for prevention of stroke and systemic embolism in patients with nonvalvular AF with one or more risk factors; and treatment and prevention of DVT and pulmonary embolism.
Venous thromboembolism in adults admitted to hospital: reducing the risk - guideline (CG92)
National Institute for Health and Care Excellence
This guidance is about the care and treatment of adults who are at risk of developing deep vein thrombosis (DVT) while in hospital in the NHS in England and Wales. It should be read in conjunction with TA 245 (published in January 2012).
Biospace Inc.
Preliminary results from GARFIELD-AF study (n=17,200) presented at the International Society on Thrombosis and Haemostasis conference have shown that fewer patients diagnosed at a hospital have good anticoagulant control vs patients diagnosed at an office/anticoagulation clinic.
Idarucizumab for Dabigatran Reversal
New England Journal of Medicine
Interim results of the RE-VERSE AD cohort study (n=90) show that idarucizumab (5g IV) rapidly and completely reversed the anticoagulant activity of dabigatran in 88 to 98% of those with elevated clotting times at baseline.
Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation
New England Journal of Medicine
In AF patients requiring warfarin interruption for an elective procedure, no bridging (placebo) was non-inferior to dalteparin bridging for the prevention of arterial thromboembolism (incidence of 0.4% v 0.3%) and decreased the risk of major bleeding (1.3% v 3.2%).
Positive Phase III data for anticoagulant antidote andexanet alfa
PharmaTimes
In Phase III ANNEXA-A trial, andexanet alfa rapidly reversed the anticoagulant effect of apixaban by 93.5%, and sustained a high level of efficacy across the two-hour infusion period. No serious adverse events were reported.
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 15th June 2015
Thromboembolic Complications and Prophylaxis Patterns in Colorectal Surgery
JAMA Surgery
US study of 16,120 patients who had undergone colorectal surgery found venous thromboembolism rates are low and largely unchanged despite increases in peri-and postoperative prophylaxis. With ~40% events occurring after discharge, this represents an area for quality improvement.
Cochrane Database of Systematic Reviews
There is low quality evidence that ursodeoxycholic acid may reduce incidence of disease, all-cause mortality and mortality in HSCT recipients. There is insufficient evidence to support use of heparin, LMWH, defibrotide, glutamine, FFP, antithrombin III, and PGE1.
Revised SPC: Plavix (clopidogrel) 75mg tablets
electronic Medicines Compendium
In section 4.5 (interactions), the list of CYP2C19 inhibitors has been amended so that it now only lists examples of strong or moderate inhibitors (ciprofloxacin, cimetidine, oxcarbazepine and chloramphenicol have been removed).
The Lancet
In a proof-of-concept study in healthy volunteers, idarucizumab (monoclonal antibody fragment that binds dabigatran) was found to immediately and completely reverse dabigatran-induced anticoagulation in a dose-dependent manner.
British Medical Journal
Some doctors have been questioning efficacy and safety of alteplase —and methodology of some of trials assessing it. Unpublished data are still missing on certain endpoints including early mortality. The MHRA is due to publish a review on alteplase towards end of 2015.
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 8th June 2015
Guideline on aspects of cancer-related venous thrombosis
British Committee for Standards in Haematology
This aims to provide healthcare professionals with clear guidance on prevention and management of venous thromboembolism (VTE) in patients with cancer and to advise on an approach to screening for cancer in patients with unprovoked VTE in whom cancer was not initially suspected.
Circulation
Danish study (n=1752) found AF patients with intracranial haemorrhage (ICH) are at very high risk of ischaemic stroke/mortality, if not on antithrombotic. Oral anticoagulant was linked to reduction in this risk, supporting feasability of its reintroduction post-ICH.
European Journal of Hospital Pharmacy
A narrative review of 21 papers found that although risk factors associated with drug-related problems (DRPs) differed greatly among these publications, comorbidity, polypharmacy and the use of specific drugs (antithrombotics, antidiabetics) were frequently associated with DRPs.
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 1st June 2015
Why do electronic health records reveal oral anticoagulant prescription after haemorrhagic stroke?
British Journal of Clinical Pharmacology
There were 134 (1.2%) subjects with electronic health records documenting previous haemorrhagic stroke (HS) prescribed warfarin during a trial. Researchers found that in ~50% patients, stroke event was miscoded as HS when physician-reported diagnosis was of cerebral infarction.
The Lancet
This study (n=21,105) found tailoring dose of edoxaban on basis of clinical factors alone prevents excess drug levels and helps to optimise risk of ischaemic and bleeding events. Data also showed that therapeutic window for edoxaban is narrower for major bleeding than thromboembolism.
The Lancet
Analysis of 4833 subjects taking warfarin found that CYP2C9 and VKORC1 genotypes identify patients who are more likely to experience early bleeding with warfarin and who derive a greater early safety benefit from edoxaban compared with warfarin during first 90 days.
National Institute for Health and Care Excellence
Guidance recommends apixaban, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults.
Early Medication Nonadherence After Acute Myocardial Infarction
Circulation
Analysis of 7425 acute MI patients treated with PCI at 216 US hospitals found that a substantial proportion report suboptimal adherence to prescribed medications, soon after MI. Moderate and low adherence was reported in 25% and 4% of patients, respectively, at 6 weeks post MI.
European Heart Journal
Meta-analysis found NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) decrease risk of fatal bleeding by 47%, case fatality due to major bleeding by 32% and all-cause mortality after a bleeding event by 43% vs. vitamin K antagonists.
Progress in Intravenous Thrombolytic Therapy for Acute Stroke
JAMA Neurology
This review traces the development of IV thrombolysis to date, considers the shortcomings of alteplase, and examines alternative thrombolytic approaches currently in the pipeline, including the role of neuroimaging and the possibility of combination therapies.
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:
Anticoagulation news items. Week commencing 25th May 2015
British Journal of Clinical Pharmacology
Reports of drug-induced liver injury associated with NOACs including acute liver failure events represented 3.7% (n = 146) and 1.7% (n = 222) of all reports for rivaroxaban and dabigatran, respectively. Disproportionality signals emerged for rivaroxaban in primary analysis.
JAMA Internal Medicine
This retrospective cohort study of patients whose warfarin therapy was interrupted for invasive diagnostic or surgical procedures (total 1812) found use of bridging increased the rate of clinically relevant bleeding (2.7% v 0.2% in those with no bridging); VTE rates were similar.
JAMA Neurology
This single-centre study reports that in patients undergoing coiling for unruptured aneurysms, use of a modified antiplatelet regimen for those with high on-treatment platelet reactivity reduced the rate of thromboembolic events vs. standard antiplatelet therapy.
Annals of Internal Medicine
This review of 9 RCTs reports that longer-duration dual antiplatelet therapy (DAPT) following drug-eluting stent placement reduced MI risk (RR 0.73, 95% CI 0.58-0.92) but increased mortality (1.19, 1.04-1.36) and major bleeding risk (1.63, 1.34-1.99]) vs. shorter-duration DAPT.
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:
Anticoagulation news items. Week commencing18th May 2015
JAMA Oncology
Analysis of 17 RCTs suggests no differences exist in the risk of substantial intraocular bleeding between NOACs and other antithrombotic drugs (vitamin K antagonists, aspirin, low-molecular-weight heparin). However, the number of events was scarce so further studies are needed.
Stroke Prevention in Atrial Fibrillation: A Systematic Review
Journal of the American Medical Association
This review highlights that stroke prevention is central to management of AF, irrespective of a rate or rhythm control strategy. Following the initial
focus on identifying low-risk patients, all others with 1 or more stroke risk factors should be offered oral anticoagulation.
Circulation
US study of 10,213 MI patients who underwent PCI and were discharged on dual antiplatelet therapy found that high maintenance dose aspirin (325mg) was linked to similar rates of major adverse cardiovascular events but greater risk of minor bleeding vs. low-dose aspirin (81mg).
Circulation
Direct oral anticoagulants demonstrate at least equal efficacy to VKAs in managing thrombotic risks in the elderly although bleeding patterns were distinct with dabigatran linked to a particularly higher risk of GI bleeding compared to VKAs.
National Institute for Health Research
This systematic review evaluated whether or not 'aspirin resistance' defined using platelet function tests (PFTs) was linked to occurrence of adverse clinical outcomes and concluded that studies investigating this were of inconsistent quality - no firm conclusions could be made.
Journal of Clinical Oncology
In patients with advanced pancreatic cancer undergoing chemotherapy, prophylactic enoxaparin was associated with a reduced rate of symptomatic VTE (6.4% vs 15.1% with no enoxaparin) and no increase in major bleeding; there was no difference in progression-free or overall survival.
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:
Anticoagulation news items. Week commencing11th May 2015
European Heart Journal
RCT (n=248; VENTURE-AF) found that use of uninterrupted rivaroxaban was feasible and bleeding and thromboembolic event rates were similar to those for uninterrupted vitamin K antagonists in patients with non-valvular atrial fibrillation undergoing catheter ablation.
European Heart Journal
In pre-specified subgroup analysis, patients randomised to lower dose edoxaban (DE) who were taking amiodarone at baseline had fewer ischaemic events compared with warfarin vs. patients not on amiodarone. Also amiodarone had no effect on relative efficacy and safety of higher DE.
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:
Anticoagulation news items. Week commencing 4th May 2015
The Lancet
In this analysis (202,417 person-yrs), a roughly 4-times increase in age-adjusted incidence and prevalence of AF in both sexes was reported. Risk of AF in both sexes doubled with each decade of age, and risk of stroke and death after diagnosis were equivalent between the sexes.
Antiplatelet therapy following transcatheter aortic valve implantation
Heart
Systematic review and pooled analysis of individual patient data (n=672) found no difference in 30-day net adverse clinical and cerebral events rate between aspirin-only or dual antiplatelet therapy following transcatheter aortic valve implantation.
Journal of the American College of Cardiology
Study (n=39,400) found low-risk patients (CHA2DS2-VASc=0 [male],1 [female]) have a truly low risk for stroke and bleeding. With 1 additional stroke risk factor (score 1 & 2 respectively), there was significant increase in event rates (particularly mortality) if non-anticoagulated.
European Heart Journal
This position paper discusses the gaps in knowledge on the effects of gender on pharmacokinetics and pharmacodynamics of cardiovascular drugs, and how such differences may influence their effectiveness and safety.
Annals of Internal Medicine
In 449 women with unexplained recurrent pregnancy loss, a daily injection of LMWH (dalteparin 5000IU) for up to 24 weeks' gestation did not improve the rate of ongoing pregnancy at 24 weeks (86.8% v 87.9%) or the live birth rate (86.0% v 86.7%) v control.
EMA approves Raplixa™ powdered fibrin sealant for surgical bleeding
European Medicines Agency
The EMA has approved Raplixa™ (fibrin sealant) for use in adults as a supportive treatment where standard surgical techniques are insufficient for improvement of haemostasis. It must be used in combination with an approved CE marked gelatin sponge (supplied separately).
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:
Anticoagulation news items. Week commencing 27th April 2015
British Medical Journal
A US analysis of almost 220 000 new users of dabigatran, rivaroxaban, or warfarin (2010-2013) found that risk of GI bleeding with dabigatran or rivoroxaban was similar to warfarin but risk exceeded that of warfarin with age, particularly in those over 75 years.
British Medical Journal
A US analysis (n= 46,000) found that neither dabigatran nor rivaroxaban was associated with a statistically significantly increased risk of GI bleeding relative to warfarin. However the study had wide confidence intervals and an increased risk of bleeding cannot be ruled out.
European Medicines Agency
The CHMP has adopted a positive opinion recommending approval of edoxaban (Lixiana™), for prevention of stroke and systemic embolism in adults with atrial fibrillation and for treatment and prevention of deep vein thrombosis and pulmonary embolism.
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:
