Anticoagulation news items. Weeks commencing 25th July 2016 and 1st August 2016
Self-monitoring and self-management of oral anticoagulation therapy
Cochrane Database of Systematic Reviews
Review of 28 RCTs (n=8,950) found a reduction in thromboembolic events in the pooled estimate of self-monitoring or self-management vs standard monitoring (HR, 0.58; 95%CI, 0.45-0.75). No reduction in all-cause mortality or incidence of major or minor haemorrhage was seen.
Economic burden of non-malignant blood disorders across Europe: a population-based cost study
The Lancet Haematology
Non-malignant disorders of the blood cost the 31 European countries €11 billion in 2012. Health-care costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for less than €1 billion (6%).
Heparin for the prevention of intraventricular haemorrhage in preterm infants
Cochrane Database of Systematic Reviews
There is very limited data on effect of prophylactic heparin on incidence and severity of intraventricular haemorrhage (IVH). Both the identified trials used
heparin in the context of maintaining umbilical line patency and not specifically to prevent germinal matrix IVH.
British Journal of Clinical Pharmacology
Study (n=2094) found that frequency of warfarin dose changes and INR monitoring events declined until around age 67, then increased as patients got older.
Heart
In a meta-analysis of 2 randomised and 12 observational studies, there was no benefit of adding a vitamin K antagonist (VKA) with regards to thromboembolism or mortality, versus antiplatelet /no therapy. However, use of a VKA was linked to increased risk of major bleeding.
BMJ Open
Australian study (n=986) found 54 (5.5%) developed venous thromboembolism (VTE), of which 25.9% (14/54) had detected VTE post-hospitalisation with increased risk if there was history of VTE, recent surgery and pulmonary conditions, suggesting potential role of thromboprophylaxis.
National Institute for Health and Care Excellence
In 2017, 30 UK GP practices will test these indicators. GPs will routinely test anyone >65 years for AF and assess how often someone with AF discusses treatment with GP. If these measures are found to improve AF identification/management, they could be rolled out in 2017/18.
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. Weeks commencing 18th July 2016
Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registryDrug Safety Alert: Warfarin - reports of calciphylaxis (syndrome of vascular calcification)
Medicines and Healthcare products Regulatory Agency
An EU-wide review of relevant evidence recently concluded that there is a reasonable possibility that on rare occasions warfarin use might lead to calciphylaxis. Healthcare professionals are advised to consider stopping warfarin and starting appropriate treatment if necessary.
Circulation
This review summarises the evidence around the management of non–vitamin K antagonist (NOACs)-related bleeding, including prevention of bleeding, general principles and supportive measures, nonspecific haemostatic agents, and NOAC-specific reversal agents.
European Heart Journal
Study (n=45,073) found the risk of the primary outcome (composite of all-cause death, re-admission with myocardial infarction or stroke) with ticagrelor vs. clopidogrel was 11.7 vs. 22.3% (HR 0.85 [95% CI: 0.78–0.93]).
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. Weeks commencing 11th July 2016
Precision Medicine for Ischemic Stroke
JAMA Neurology
In this article, the authors discuss the future of precision medicine in the field of ischaemic stroke, first looking at the current status of genetic approaches, and then exploring the status of phenotype-based delineations.
Volunteers wanted to help determine the future of pharmacovigilance
Medicines and Healthcare products Regulatory Agency
Web-RADR: Recognising Adverse Drug Reactions is running a survey for healthcare providers, patients, and consumers of medicines to help develop the next generation of online side-effect reporting software.
New product: ALPROLIX (eftrenonacog alfa) powder and solvent for solution for injection
electronic Medicines Compendium
Eftrenonacog alfa is licensed for the treatment and prophylaxis of bleeding in patients with haemophilia B (congenital factor IX deficiency).
Direct oral anticoagulants: unique properties and practical approaches to management
Heart
This is a review of the indications and dosing considerations, clinical efficacy and safety, laboratory monitoring and reversibility considerations and peri-procedural management of the direct oral anticoagulants (DOACs), highlighting strategies to ensure safe and effective DOAC.
European Medicines Agency
This review has been initiated following a recent study which suggested that inhibitors develop more frequently in patients on factor VIII (F-VIII) medicines made by DNA recombinant technology than in those receiving (F-VIII) derived from blood.
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. Weeks commencing 4th July 2016
Risk of Bleeding and Thrombosis in Patients 70 Years Or Older Using Vitamin K Antagonists
JAMA Internal Medicine
Matched cohort study (n=3313) found compared to patients aged 70-79, those aged 80-89 had similar risk of bleeding, whereas those ≥90 had mildly increased risk of bleeding. Patients in their 80s and 90s had markedly higher risk of thrombosis vs. patients in their 70s.
Journal of the American Medical Association
Chinese study (n=2933) found after day 90 follow-up, clopidogrel-aspirin (CA) reduced the rate of new stroke in the non-carriers but not in carriers of loss-of-function alleles vs aspirin alone.
Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial
Circulation
In this analysis of ENGAGE AF-TIMI 48 study (n=14,071), findings from prespecified renal subgroups defined by a CrCl of 30-50 and >50mL/min were similar to overall trial results in which high dose edoxaban was comparable to warfarin for prevention of stroke/systemic embolism.
The Lancet Haematology
Analysis (n=771 with cancer) found recurrent venous thromboembolism (VTE) occurred in 4% of patients on edoxoban and 7% on warfarin (HR 0.53, 95% CI 0.28-1.00) concluding that edoxoban is non-inferior to warfarin in the treatment of patients with cancer with VTE.
Deep vein thrombosis and pulmonary embolism
The Lancet
This seminar focuses on the epidemiology, diagnosis, and treatment of deep vein thrombosis of the legs and pulmonary embolism as well as looking at future research in this area.
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. Weeks commencing 27th June 2016
British Journal of Clinical Pharmacology
Meta-analysis of 8 cohort studies suggest a slightly higher risk of gastrointestinal bleeding with dabigatran use compared with warfarin (risk ratio 1.21; 95% CI, 1.05-1.39), but no significant difference was found between rivaroxaban and warfarin.
Chest
Study (n=94,897) found direct oral anticoagulants (DOACs) had decreased risk for major bleeding vs vitamin K antagonists when estimated creatinine clearance (eCrCL) 50-80mL/min (RR 0.87, 95%CI 0.81-0.93). However, DOACs' bleeding risk differs from each other when eCrCL<50mL/min.
Circulation
Analysis (n=12,612) found among those with on-treatment worsening renal function, rivaroxaban (RV) was linked to lower rates of stroke/systemic embolism vs. warfarin, without increase in composite bleeding endpoint. This was not seen in patients with stable renal function on RV.
Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF
European Heart Journal
Two-year outcomes from ongoing, global observational study (n=17,162) found death was most frequent adverse outcome. Stroke-related mortality was not most frequent cause of death, suggesting that as well as anticoagulation, a more comprehensive approach to management is needed.
Biospace Inc.
Researchers have developed a new, free mobile app, "Aspirin-Guide" that calculates both the CVD risk score and the bleeding risk score for individual patients, and helps clinicians decide which patients are appropriate candidates for the use of low-dose aspirin (75 - 81mg daily).
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. Weeks commencing 13th June 2016 and 20th June 2016
Heart
Study (n=3129) found elderly (age ≥75 years) patients with atrial fibrillation in both Japan and the UK are at similarly high risk of stroke and death. Appropriate oral anticoagulation was still underused (<60%) in both populations.
Eyes on Evidence: Perioperative anticoagulation for people with atrial fibrillation
National Institute for Health and Care Excellence
A commentary is provided on RCT in people with AF who stopped taking warfarin before elective surgery/invasive procedure, which found people who did not receive 'bridging' heparin had a lower risk of bleeding and no higher risk of thromboembolism than those who received it.
British Medical Journal
Danish cohort study (n=61,678) found all NOACs seem to be safe and effective alternatives to warfarin (WF) in a routine care setting. No significant difference was found for ischaemic stroke. Risks of death, any or major bleeding were lower for apixaban and dabigatran vs. WF.
British Medical Journal
In trial (n=18,201),~75% patients had polypharmacy; this subgroup had increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic/bleeding complications. Apixaban was more effective than warfarin regardless of number of concomitant drugs.
The Lancet Neurology
Over 90% stroke burden (SB) is attributable to modifiable risk factors, and achieving control of behavioural/metabolic risk factors could avert over three-quarters of global SB. Air pollution has emerged as a significant contributor to SB especially in low/middle-income countries.
National Institute for Health Research Signal
This is an expert commentary of a meta-analysis which found that bivalirudin as an alternative to heparin to prevent clotting during percutaneous coronary intervention may be ineffective in preventing recurrence of blockage or further heart attacks.
British Medical Journal
The PEGASUS-TIMI-54 trial was one of first to inform management of high risk patients, but this analysis has shown that real world patients who survive ≥1 year after acute MI are at yet greater risk, amplifying potential of dual antiplatelet therapy to improve prognosis.
Risk of venous thromboembolism in cancer patients treated with epoetins or blood transfusions
British Journal of Clinical Pharmacology
Study of 69,888 patients identified 3316 cases of venous thromboembolism (VTE). There was a higher risk of VTE with epoetins (OR 1.31 (95% CI 1.03-1.65)), transfusions (2.33 (2.03-2.66)), and epoetins and transfusions (2.24 (1.34-3.77)).
British Journal of Clinical Pharmacology
This review of 5 trials (n=72,673) found that direct oral anticoagulants were not superior to warfarin for prevention of stroke and systemic embolic events (RR=0.97 95% CI=0.85-1.11) in European patients (n=32,089), but were with patients from other regions (0.72, 0.63-0.83).
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. Weeks commencing 30th May 2016 and 6th June 2016
Gut
These guidelines refer to patients undergoing elective endoscopic gastrointestinal procedures, and make recommendations on the management antiplatelet/anticoagulant therapy based on the risk of procedural haemorrhage vs. thrombosis if therapy is discontinued.
European Heart Journal
This guide has been updated including new information with a balanced guide in the areas where prospective data are still lacking. Changes include a discussion on the definition of 'non-valvular AF' and eligibility for DOAC therapy and finalised information on edoxaban.
The Lancet Neurology
Analysis (n= 6756 in 9 trials of alteplase vs. control) found that in alteplase group, net outcome is predicted both by time to treatment (faster time increasing % achieving excellent outcome) and stroke severity (more severe increasing absolute risk of intracerebral bleed).
British Medical Journal
Non-inferiority trial (n=518) found that stopping elastic compression stockings (ECS) after one year in compliant patients with proximal deep venous thrombosis (DVT) seemed not to be non-inferior to continuing ECS therapy for 2 years, with an NNT of 14.
European Heart Journal
This review provides a perspective on the use of antithrombotic treatments in patients with both AF and HF, and in patients with HF and sinus rhythm, with particular attention to the NOACs, and provides background for therapeutic, outcome and trial improvement.
Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients
New England Journal of Medicine
In this RCT (n=7513), the primary efficacy outcome of composite asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism was not statistically significant (6.9% for betrixaban v 8.5% for enoxaparin in the group with raised d-dimer levels.
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. Weeks commencing 23rd May 2016
FDA approves Afstyla for patients with haemophilia A
PharmaTimes
Afstyla, a novel recombinant factor VIII single-chain therapy, designed for long-lasting protection from bleeds with 2-3 x weekly dosing. It can also be used as on-demand treatment to control bleeds, and in perioperative management of bleeding.
New England Journal of Medicine
This feature article begins with a case highlighting a common clinical problem, cryptogenic stroke. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.
British Medical Journal
A comparison of bleeding rates seen in a cohort (n=21934) of patients with AF treated with warfarin v dabigatran with what was predicted using risk assessment models & data from RCTs showed good correlation between models & real-life but RCTs underestimate risk of major bleeding.
Reversal of the anticoagulant effect of dabigatran: idarucizumab (ESNM73)
National Institute for Health and Care Excellence
This review looks at the evidence for the efficacy/safety of idarucizumab for reversing the anticoagulant effect of dabigatran etexilate. There are
currently no other licensed agents to reverse the anticoagulant effect of dabigatran etexilate (or any other NOAC).
Circulation
This review, based on 2 case vignettes, discusses dual antiplatelet therapy in the management of patients with acute coronary syndromes and those undergoing percutaneous coronary intervention, in the context of balancing optimal duration with the risk of adverse bleeding effects.
Use of antipsychotics and risk of myocardial infarction: a systematic review and meta-analysis
British Journal of Clinical Pharmacology
This review of 9 observational studies found that the odds for developing an MI were higher with antipsychotic users vs never users (OR=1.88, 95%CI=1.39-2.54). Short term users (<30 days) and those with schizophrenia had a more pronounced risk.
European Heart Journal
This review of 12 studies (n=99,996) found that non-paroxysmal AF was associated with higher rates of thromboembolism than parosxysmal AF (unadjusted RR=1.355, 95%CI= 1.169-1.571).
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. Weeks commencing 16th May 2016
The Lancet
Data from 12 trials (n=15,778) found aspirin reduced 6 week risk of recurrent ischaemic stroke (IS) vs. placebo by ~ 60% (HR 0.42, 95% CI, 0.32–0.55, p<0.0001) and disabling or fatal IS by ~70% (0.29, 0.20–0.42, p<0.0001), with greatest benefit in patients with TIA/minor stroke.
Coronary-Artery Bypass Grafting
New England Journal of Medicine
This review covers evidence from trials of CABG vs. medical therapy or vs. percutaneous coronary intervention, as well as complicating factors, indications and evaluation for CABG, morbidity and mortality, and secondary prevention.
Which Oral Anticoagulant for Atrial Fibrillation?
Journal of the American Medical Association
This Medical Letter review summarises the newly available oral anticoagulants and compares them with commonly prescribed warfarin.
South West Medicines Information & Training
This updated Medicines Q&A reviews the current literature regarding the use of prophylactic doses of low molecular weight heparins in patients with renal impairment.
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. Weeks commencing 9th May 2016
Clinical impact and course of major bleeding with edoxaban versus vitamin K antagonists
Thrombosis and Haemostasis
Analysis of major bleeding events from Hokusai-VTE study (n=8240) suggests edoxaban associated major bleeding events have similar presentation/course compared to those with vitamin K antagonist (56 and 65 events, respectively) in patients treated for venous thromboembolism.
British Medical Journal
This study (n=5,443,916) found that for the same dose of oestrogen, desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial thromboembolism compared with levonorgestrel.
Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke
New England Journal of Medicine
This open label study (n=3310) in mainly Asian patients low-dose alteplase (tPA) did not show non-inferior to standard-dose tPA with respect to death and disability at 90 days. There were significantly fewer symptomatic intracerebral haemorrhages with low-dose tPA.
Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack
New England Journal of Medicine
This RCT (n=13,199) found that ticagrelor was not superior to aspirin in reducing the rate of stroke, myocardial infarction or death at 90 days (HR=0.89, 95%CI= 0.78-1.01, p=0.07).
The Lancet
In this open label trial (n=190) the odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted OR 2•05, 95% CI 1•18–3•56).
BMJ Open
This review identified 3 models, HERDOO2 score, Vienna prediction model and DASH score, for predicting the recurrence risk of VTE and concluded that none of these can be considered ready for use until further external, robust validation is performed in new data.
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
