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:
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Anticoagulation news items. Weeks commencing 2nd May 2016
The Lancet Haematology
Meta-analysis of 6 RCTs (n=1462) found use of elastic compression stockings in patients with DVT does not significantly reduce development of post thrombotic syndrome, however current body of evidence is limited, and further studies are needed to establish role of this therapy.
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 25th April 2016
Antithrombin for the prevention of intraventricular hemorrhage in very preterm infants
Cochrane Database of Systematic Reviews
Administration of antithrombin seems not to reduce incidence/severity of intraventricular haemorrhage in very preterm infants. Limited evidence is available on other clinically relevant outcomes. Given imprecision of estimate, this review cannot provide definitive answer.
Cochrane Database of Systematic Reviews
Moderate quality evidence suggests extended-duration anticoagulants to prevent VTE should be considered for people undergoing hip replacement surgery, although the benefit should be weighed against the increased risk of minor bleeding.
The left atrial appendage: from embryology to prevention of thromboembolism
European Heart Journal
This article describes the anatomy and function of the left atrial appendage (LAA) and current imaging tools for the identification of anatomical varieties. It also covers pathogenetic mechanisms of LAA thrombosis in AF patients, and examines the evidence on treatment strategies.
County Durham and Darlington NHS Foundation Trust
This shared learning guide presents a care pathway for the INR self-testing service, including the protocol for patient selection and training and the specification for the Health Call INR service, developed by clinicians working in the anticoagulation clinic.
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. Weeks commencing 18th April 2016
Pre-treatment with P2Y12 inhibitors in ACS patients: who, when, why, and which agent?
European Heart Journal
This review evaluates the available evidence on the value of pre-treatment with oral and intravenous P2Y12 inhibitors (clopidogrel, ticagrelor, prasugrel, and cangrelor) that can be administered to patients in whom coronary angiography followed by a possible PCI is planned.
British Medical Journal
This review (10 RCTs) shows that in selected patients, endovascular treatment given within 6-8hrs after ischaemic stroke involving large vessels leads to improved functional outcome at 90 days without increased mortality vs medical care alone.
JAMA Neurology
This meta-analysis (9 studies; 2479 patients) shows that high cerebral microbleed (CMB) burden on pretreatment MRI is independently associated with symptomatic intracerebral haemorrhage in patients with acute ischaemic stroke treated with iv thrombolysis.
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. Weeks commencing 11th April 2016
Annals of Internal Medicine
This systematic review concluded that consideration of the safety of primary prevention with aspirin requires an individualized assessment of aspirin's effects on bleeding risks and expected benefits because absolute bleeding risk may vary considerably by patient.
Annals of Internal Medicine
In CVD primary and secondary prevention trials, aspirin reduced both 20-year colorectal cancer (CRC) mortality (n= 14033) and CRC incidence 10 to 19 years after initiation. (n=47464) (RR, 0.67 [CI, 0.52 to 0.86] and 0.60 [CI, 0.47 to 0.76], respectively).
Annals of Internal Medicine
This updated systematic review (11 RCTs) found a beneficial effect of aspirin (including at doses of 100mg or less per day) in reducing nonfatal MI
(absolute risk reduction, 0.15 to 1.43 events per 1000 person-years). Older adults seem to achieve a greater relative MI benefit.
European Heart Journal
This analysis (n=17913) found that in patients with AF treated with oral anticoagulants, higher BMI was associated with a lower risk of all-cause
mortality vs. normal BMI [overweight: HR 0.67 (95% CI 0.59–0.78); obese: HR 0.63 (95% CI 0.54–0.74), P < 0.0001].
The Lancet Neurology
Study (n=50) found proportion of patients with INR ≤1.2 within 3 hours of treatment initiation was achieved in 9 vs. 67% of patients given fresh frozen plasma and prothrombin complex concentrate, respectively (p=0•0003). The trial was stopped because of safety concerns.
Biospace Inc.
Alprolix® (eftrenonacog alfa), is a recombinant factor IX Fc fusion protein therapy for the treatment of haemophilia B. An application for marketing authorisation was submitted in EU in June 2015. The COMP's recommendation is now referred to the EC.
Circulation
This article compares the different stroke stratification schemes, highlighting interpretation difficulties and pitfalls as well as assessing the net benefit of stroke prophylactic treatment vs. alternative treatments.
Stroke prevention in atrial fibrillation in patients with Chronic Kidney Disease (CKD)
Circulation
This article presents a case of a 68 year old woman with hypertension, diabetes and congestive heart failure presenting with palpitations. It assesses stroke risk and looks at different options for anticoagulation in CKD.
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. Weeks commencing 4th April 2016
European Heart Journal
The benefit of ticagrelor for long-term secondary prevention in patients with prior MI and ≥1 additional risk factor appeared more marked in patients continuing on or re-starting after only a brief interruption of P2Y12 inhibitors, compared with patients off them for > 1 year.
The Lancet
The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) score performed better than HAS-BLED and ORBIT scores in patients with AF on anticoagulants from the ARISTOTLE and RE-LY trials.
Indiscriminate Testing for Heparin-Induced Thrombocytopenia: A Teachable Moment
JAMA Internal Medicine
This case report illustrates the ramifications of overtesting, and advises that it is crucial to consider other causes of thrombocytopenia and determine pretest probability to guide management whenever heparin-induced thrombocytopenia is suspected.
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. Weeks commencing 29th March 2016
Effect of prior clopidogrel use on outcomes in medically managed acute coronary syndrome patients
Heart
Compared with medically managed patients newly started on clopidogrel (CP) in TRILOGY ACS trial, patients previously on CP had a higher risk of CV events. There were no differences in outcomes as stratified by prior CP use by randomised treatment assignment (prasugrel or CP).
Circulation
Review of 11 RCTs (n=33,051 who received predominantly newer-generation drug eluting stents) found moderately strong evidence that prolonged dual antiplatelet therapy entails a trade-off between reductions in stent thrombosis and MI and increases in major haemorrhage.
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 21st March 2016
The Lancet Haematology
Analysis suggests extended treatment with edoxaban (ED) is as effective as warfarin (WF) [incidence recurrent venous thromboembolism between 3 and 12 months = 0·3% (11 of 3633) with ED and 0.4% (14 of 3594) with WF; HR 0.78, 95% CI 0.36–1.72] and linked to less major bleeding.
Astra Zeneza announces that ticagrelor fails to meet primary efficacy endpoint in SOCRATES trial
PharmaTimes
The drug failed on the primary efficacy endpoint of increasing the time to first occurrence of stroke (ischaemic or haemorrhagic), myocardial infarction or death vs aspirin in patients who have experienced an acute ischaemic stroke or transient ischaemic attack.
Positive results in first six months for anticoagulant hospital referral service
Pharmaceutical Services Negotiating Committee
Since launch (6 months) 138 patients have been referred to Swindon and Wiltshire Local Pharmaceutical Committee anticoagulant referral service with Great Western Hospital. This report highlights the positive outcomes experienced.
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:
