National Institute for Health and Care Excellence
A DRAFT update of NICE guideline CG92 (published January 2010), which includes new and updated recommendations on the risk assessment and prophylaxis of people at risk of venous thromboembolism, is now available for consultation.
Bayer halts Phase III study of rivaroxaban in embolic stroke
PharmaTimes
Bayer has halted a Phase III study investigating rivaroxaban in patients with embolic stroke of undetermined source after it showed no improvements in efficacy when compared to aspirin. Bleeding rates were low overall but higher in the rivaroxaban arm (no data presented).
In Use Product Safety Assessment report for Inhixa (enoxaparin biosimilar)
Specialist Pharmacy Service
This assessment, produced using the validated UKMi product assessment tool, discusses practical safety considerations associated with the introduction of this biosimilar product, including the need to ensure prescribing of product by brand name.
European Heart Journal
Review (n=1850 with MI) found that among those with a left ventricular thrombus given a vitamin K antagonist, those with a time in therapeutic range (TTR) ≥50% had a lower risk of thromboembolism vs those with TTR <50% (2.9% vs 19%, p=0.036) with no difference in major bleeding.
Indications for anticoagulant and antiplatelet combined therapy
British Medical Journal
Review notes combination treatment increases risk of bleeding, and this risk should be estimated and discussed with patients to guide treatment decisions (e.g. using risk scores such as HAS-BLED). Consideration should be given to addition of H2 antagonist or proton pump inhibitor.
Association Between Use of Antithrombotic Medication and Hematuria-Related Complications
Journal of the American Medical Association
Canadian retrospective cohort study (n=808,897) found that over a median follow-up of 7.3 years the rate of haematuria complications was higher in those exposed to antithrombotics vs those not exposed (123.95 vs 80.17 per 1000 person years, Rate Ratio 1.44, 95% CI 1.42-1.46).
Journal of the American Medical Association
Taiwanese study (91,330 patients on NOACs) found that those on concurrent amiodarone, fluconazole, rifampicin and phenytoin had a significant increased risk of major bleeding vs NOAC use alone (difference +13.94, +138.46 +36.90 and +52.31 incidents per 1000 person years).
Thrombosis and Haemostasis
Combined data from the EINSTEIN, AMPLIFY and HOKUSAI-VTE studies found that factor Xa inhibitor associated major bleeding events in these studies had a less severe presentation and similar course compared to vitamin K antagonists.
Shortage of abciximab (Reopro) 2mg/ml solution for injection or infusion
Specialist Pharmacy Service
There is a potential 6 month supply issue affecting abciximab from October through till March 2018. This memo advises on alternative treatment options in the interim should stock run out.
JAMA Internal Medicine
This secondary analysis of a RCT that involved 3310 patients with acute ischaemic stroke found no clear differential benefits of low-dose alteplase compared with standard-dose alteplase in disability outcomes, irrespective of age, race/ethnicity, and neurological severity.
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
Miconazole (Daktarin): over-the-counter oral gel contraindicated in patients taking warfarin
Medicines and Healthcare products Regulatory Agency
Patients taking warfarin should not use over-the-counter miconazole oral gel. If concomitant use is planned via prescription, the anticoagulant effect of warfarin should be monitored carefully. Patients who experience signs of bleeding should seek immediate medical attention.
American Journal of Cardiology
Review of 13 studies (3 RCTs and 10 observational studies, total n=4,878) found no significant difference in the risk of major bleeding, systemic thromboembolism and symptomatic stroke/TIA, though the evidence was not of high quality.
BMJ Open
Cohort study showed an increasing proportions of patients with non-valvular AF receiving anticoagulant therapy (16.7% rise), together with similar reductions in antiplatelet (16.8% decrease). The proportion of patients not receiving antithrombotics remained the same (15%).
Journal of the American Medical Association
RCT (n=1,650) found that fewer patients in the geno-type guided group had a composite outcome event (major bleeding, INR>4, VTE or death) vs clinically guided warfarin (10.8% vs 14.7%, RR 0.73, 95% 0.56 to 0.95).
Biospace Inc.
This study (n=215) reports that more patients on lusutrombopag vs placebo (64.8% vs 29.0%) met the primary efficacy endpoint (defined as proportion of patients who required no platelet transfusion prior to the invasive procedure) and no rescue therapy for bleeding post procedure.
Circulation
Median onset-to-revascularisation time was 202 minutes for direct presentation vs 311 minutes for interhospital transfer in 984 patients undergoing mechanical thrombectomy for severe stroke (p<0.001). Mortality did not differ and IV alteplase did not impact outcomes.
Biospace Inc.
The NDA was based on data from two Phase III trials, ADAPT-1 and ADAPT-2, that evaluated the efficacy and safety of avatrombopag for the treatment of severe thrombocytopenia (<50,000/μL) in patients with chronic liver disease who are scheduled to undergo a procedure.
Diagnosis and management of postpartum haemorrhage
British Medical Journal
Review notes this is second leading direct cause of maternal deaths in UK. It recommends tranexamic acid for all women with atonic and traumatic postpartum haemorrhage as well as for ongoing haemorrhage during a caesarean section.
National community pharmacy oral anticoagulant safety audit
Specialist Pharmacy Service
This audit will provide insight on patient awareness of key information about their anticoagulant, use of alert cards and compliance with monitoring requirements. Results will be used to inform a national update of patient held oral anticoagulant information and alert cards.
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
Annals of Internal Medicine
10 studies (n=2,316) found a 12 month prevalence of cancer after VTE of 5.2%. The point prevalence of cancer was higher in those with extensive screening vs limited screening initially (OR 2.0, 95% CI 1.2 to 3.4), but not at 12 months (OR 1.4, 95% CI 0.89 to 2.1).
Gastroenterology
Review of 8 studies (n=353) found that more patients given anticoagulants underwent portal vein thrombosis recanalization vs no treatment (71% vs 42%, p<0.0001). There was no difference in major or minor bleeding in the 6 studies that reported this.
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
Journal of Thrombosis and Haemastasis
Dabigatran vs warfarin, was associated with comparable incidence of first hospital admission (incidence rate ratio, 0.92; 95% CI, 0.66-1.28) but higher risk of 30-day readmission with respect to bleeding (adjusted HR, 2.87; 95%CI, 1.10-7.43) in 51,946 Hong Kong patients with AF.
European Heart Journal
In the absence of clinical guidance, this review discusses the evidence and proposes management strategies for antiplatelet therapy in patients with acute coronary syndrome and thrombocytopenia.
JAMA Neurology
This RCT (n=195) reports in patients with mild acute ischaemic stroke and AF, new ischaemic lesions or intracranial haemorrhage (noted on MRI imaging) after 4 weeks occurred in 49.5% of patients receiving rivaroxaban v 54.5% receiving warfarin (nonsignificant difference, p=0.49).
Heart
Subgroup analysis of the On-TIME 2 trial (n=984) found that baseline N-terminal pro-B-type natriuretic peptide level predicted long-term mortality. In those with high levels, early prehospital treatment with tirofiban significantly reduced 30-day and 1-year mortality vs placebo.
European Medicines Agency
The European Medicines Agency has concluded there is no clear evidence of a difference in risk of inhibitor development between recombinant factor VIII medicines and those derived from plasma. The risk of inhibitor development should be evaluated individually for each medicine.
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
European Medicines Agency
The PRAC has confirmed its previous conclusion that there is no clear and consistent evidence of a difference in the incidence of inhibitor development between the two classes of factor VIII medicines: plasma-derived and made with recombinant DNA technology.
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
The Lancet
Guided de-escalation of antiplatelet therapy (one week prasugrel then one week clopidogrel, followed by maintenance treatment dictated by platelet function testing) was non-inferior to 12 months prasugrel for net clinical benefit at one year (7% v 9%; HR 0.81; 95% CI 0.62-1.06]).
Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation
New England Journal of Medicine
In patients with AF who had undergone PCI (n= 2725), dabigatran (110 mg or 150 mg bd) plus P2Y12 inhibitor (clopidogrel or ticagrelor) resulted in risk of major or clinically relevant non-major bleeding events that was significantly lower than risk with warfarin triple therapy.
Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease
New England Journal of Medicine
In patients with stable atherosclerotic vascular disease (n=27,395), rivaroxaban (2.5 mg bd) plus aspirin led to better CV outcomes but more major bleeding events vs aspirin. Rivaroxaban (5 mg bd) did not result in better CV outcomes vs aspirin and more major bleeding events.
The Lancet
Educational intervention (providers and patients, with regular monitoring and feedback), aimed to improve use of oral anticoagulation in patients with AF, resulted in an increase in patients treated with oral anticoagulants (68% to 80%) vs usual care (64% to 67%).
Bivalirudin versus Heparin Monotherapy in Myocardial Infarction
New England Journal of Medicine
This Swedish registry-based study (n=6006) reports among patients undergoing PCI for MI, the rate of the composite of death from any cause, MI, or major bleeding was similar among those who received bivalirudin vs heparin monotherapy (12.3% vs 12.8%, HR 0.96; p=0.54).
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
FDA grants priority review to licensing application for haemophilia drug emicizumab
Reuters Health
Roche said submission is based on positive data from phase 3 study in adolescents/adults with haemophilia A with inhibitors (IHs) and interim phase III results in children. It said ~30% patients develop IHs limiting treatment options and increasing risk of life-threatening bleeds.
NIHR Signal: Drug reduces deaths from bleeding after childbirth
National Institute for Health Research Signal
Expert commentary is provided for an RCT (20,600 women with post-partum haemorrhage) which found that IV tranexamic acid reduced the risk of death from bleeding vs placebo. The challenge is to promptly implement the early use of tranexamic acid into best practice.
Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets. S2TOP-BLEED
Neurology
A prediction model for major bleeding in patients with a TIA or ischaemic stroke on antiplatelets was developed following review of data from 6 RCTs. Authors claim that the S2TOP-BLEED score had a reasonable external validation but slightly underestimated the major bleeding risk.
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
Resubmission of licence application for andexanet alfa accepted by the FDA
Biospace Inc.
The resubmission contains supplementary information that had been requested by the FDA. Andexanet alfa is a factor Xa inhibitor reversal agent. In December 2016, following a market authorisation application. In the EU additional data from the manufacturers had also been requested.
Update on antithrombotic therapy after percutaneous coronary revascularisation
The Lancet
This article, the third in a Series of three about percutaneous coronary intervention, provides an update on antithrombotic therapy after percutaneous coronary revascularisation, discussing current available evidence and how to integrate these findings into clinical decisions.
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
Disease understanding in patients newly diagnosed with atrial fibrillation
Heart
Survey analysis (1,004 responses) found that about half of patients with new-onset atrial fibrillation understood the benefits of anticoagulation at the time of diagnosis and understanding improved over the first 6 months. Authors suggest a need for more ongoing patient education.
New product: Inhixa (enoxaparin biosimilar) solution for injection in prefilled syringe
electronic Medicines compendium
Inhixa (first enoxaparin biosimilar launched in the UK) is licensed for the same indications as Clexane® and is available in the following strengths: 2,000 IU (20mg) in 0.2mL, 4,000 IU (40mg) in 0.4mL, 6,000 IU (60mg) in 0.6mL, 8,000 IU (80mg) in 0.8mL, 10,000 IU (100mg) in 1mL.
European Heart Journal
Rates of major adverse CV events were similar in all treatment arms, but some secondary outcomes varied by stent type. Prolonged dual antiplatelet therapy was linked to lower MI incidence in patients with an everolimus/zotarolimus-eluting stent but a higher bleeding rate.
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
The Lancet Neurology
In patients with acute stroke, achievement of an excellent functional outcome (modified Rankin Scale score 0–1) at 3 months was similar for tenecteplase (64%) and alteplase (63%). Further trials are needed to establish whether tenecteplase is non-inferior to alteplase.
Midlands Therapeutics Review and Advisory Committee
Commissioners should ensure robust processes/local initiatives are in place to identify patients with AF at increased risk of stroke, and a record made of decision whether or not to proceed with treatment. They should refer to NICE CG 180 and range of decision support tools.
European Heart Journal
In trial of 422 DOAC-treated patients requiring invasive procedure, last dose of DOAC 3 days before procedure resulted in minimal pre-procedural anticoagulant effect for almost all patients. Moderate renal impairment and antiarrhythmics should result in longer DOAC interruption.
Drug Trial Snapshots: Bevyxxa (betrixaban)
US Food and Drug Administration
This Drug Trials Snapshot is intended as a tool for consumers to use when discussing risks/benefits of betrixaban for the prevention of venous thromboembolism (VTE) in hospitalised adults at risk for developing VTE. The FDA approval was based on evidence from one clinical trial.
Mechanical versus bioprosthetic aortic valve replacement
European Heart Journal
Review notes main reason to opt for bioprosthesis is to avoid lifelong anticoagulation (AC) which has resulted in increase in use of bioprosthetic as opposed to mechanical valves. Currently, there is not enough evidence to support routine AC after bioprosthetic valve implantation.
Sanofi UK
Product information has been harmonised in EU. Strength will now be expressed both in IU of anti-Xa activity and in mg. Treatment dose for DVT/PE has been clarified. Use in end stage renal disease (creatinine clearance <15 ml/min) is not recommended outside haemodialysis setting.
Shortage of enoxaparin injection: alternative treatment options
Specialist Pharmacy Service
In light of current shortage of enoxaparin injection (all strengths), a table of licensed low molecular weight heparins has been drawn up to compare/contrast key prescribing parameters and a section on DOACs included to highlight where they could be used in certain settings.
Antiphospholipid syndrome and pregnancy: Pathogenesis to translation
Arthritis & Rheumatology
Antiphospholipid syndrome (APS) is an autoimmune condition linked with thrombosis and adverse pregnancy outcomes. Review discusses abnormal placental development, prediction of adverse pregnancy outcomes in APS and SLE, and potential targets to prevent obstetric APS.
New England Journal of Medicine
Subarachnoid hemorrhage without preceding trauma is caused by rupture of an intracranial aneurysm in 80% of cases. This review discusses signs /symptoms, evaluation, medical interventions to reduce risk of rupture, treatment of ruptured cerebral aneurysms and of complications.
American Journal of Medicine
Meta-analysis of 8 trials (n=12,917) found no significant difference in CV mortality/MI/major bleeding between shortterm and 12-month/extended dual antiplatelet therapy (eDAPT).However, 12-month DAPT showed significantly higher risk of MI but reduced major bleeding risk vs. eDAPT.
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
