NIHR Signal: Adding a third antiplatelet drug after a stroke increases harms but not benefits

National Institute for Health Research Signal

Expert commentary notes even with rapid implementation of secondary prevention, risk of recurrent ischaemic stroke is high with greatest risk in first 30 days, hence temptation to add antiplatelet agents, though this results in no additional benefit and increases bleeding.

Dual Antiplatelet Therapy in Transient Ischemic Attack and Minor Stroke With Different Infarction Patterns: Subgroup Analysis of CHANCE Randomized Clinical Trial

JAMA Neurology

Imaging substudy of CHANCE (n=1089) found infarction (IF) patterns can efficiently stratify risk of recurrent stroke within 3 months of non-cardioembolic TIA/minor ischaemic stroke. Patients with multiple acute IFs received most pronounced clinical benefit from dual antiplatelets.

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 CHMP does not recommend approval of the factor Xa inhibitor betrixaban (Dexxience), intended for the prevention of venous thromboembolism

European Medicines Agency

The CHMP considered that the main study did not satisfactorily show that its benefits outweighed its risk when used for preventing blood clots in patients admitted to hospital for recent medical illness. It was approved in the US in June 2017.

Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism- guidance (NG89)

National Institute for Health and Care Excellence

This guideline aims to help healthcare professionals identify people most at risk and describes interventions that can be used to reduce the risk of venous thromboembolism (VTE).

Non-Vitamin K Antagonist Oral Anticoagulants and Risk of Serious Liver Injury

Journal of the American College of Cardiology

Analysis of Canadian administrative data (n=51,887) found current use of NOACs was not linked with increased risk of serious liver injury in patients without/with prior liver disease vs. use of vitamin K antagonists (HR:0.99;95% CI:0.68-1.45 and 0.68;0.33-1.37 respectively).

Association between Nonsteroidal Anti‐inflammatory Drugs and Atrial Fibrillation among a Middle‐aged Population: A Nationwide Population‐based Cohort

British Journal of Clinical Pharmacology

Taiwanese study (n= 57,058) reported that NSAID users had elevated risk of AF vs non‐users (adjusted OR=1.18, 95% CI: 1.14‐1.23). Users of non‐selective, and combined selective and non‐selective NSAIDs had elevated risk of AF (1.18; 1.13‐1.23 and 1.30; 1.21‐1.39, respectively).

Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation

European Heart Journal

This RCT (n=633) reports primary outcome events (bleeding, stroke, or death) were observed in 6.9% of patients on apixaban, vs 7.3% of patients on vitamin K antagonists during ablation (difference −0.4%, non-inferiority P = 0.0002 based on definition used).

British Society of Haematology Guideline: management of thrombotic and haemostatic issues in paediatric malignancy

British Society for Haematology

The purpose of this guideline is to provide information and guidance on the management of venous thromboembolism (VTE) and bleeding complications of cancer and its treatment especially for children with leukaemia and other forms of cancer.

British Society of Haematology Guidelines on the spectrum of fresh frozen plasma and cryoprecipitate products: their handling and use in various patient groups in the absence of major bleeding

British Society for Haematology

This revised guideline discusses administration of fresh frozen plasma (FFP) primarily for 3 indications: prevention of bleeding, to stop bleeding (therapeutic) or for plasma exchange, suggesting many indications in patients without major bleeding are not substantiated.

The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

European Heart Journal

This guide addresses management of non-vitamin K antagonist oral anticoagulants in various clinical situations eg how to deal with dosing errors, oral anticoagulant plasma level measurement (rare indications, precautions and potential pitfalls), management of bleeding etc.

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

Revised SPC: Urokinase products

electronic Medicines compendium

Diluent for further dilution, previously unspecified, is now named as sodium chloride 0.9 % solution for injection. SPC now advises that after reconstitution and further dilution in glucose 5% / 10%, urokinase solution should be used immediately, due to risk of loss in activity.

Effectiveness of new antiplatelets in the prevention of recurrent myocardial infarction

Heart

Real-world study (n=1047 cases;2234 controls) found recurrent MI risk is lower with ticagrelor or prasugrel vs clopidogrel;magnitude of which was larger than observed effect in trials: OR 0.65;95% CI 0.52 -0.81 and 0.71;0.53-0.96 vs 0.84 0.77-0.9 and 0.81;0.73- 0.90, respectively.

Imaging is the only way to diagnose blood clots in pregnancy

National Institute for Health Research Signal

An expert commentary is provided on this study which concluded biomarkers, including the D-dimer test were not useful in diagnosing PE and DVT, and imaging tests are therefore required in this population.

6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial

The Lancet

RCT (n=2,712) found that 6 months dual therapy was non-inferior to 12 months or longer in terms of composite risk of all cause death myocardial infarction, or stroke (absolute risk difference +0.5%, upper limit of 95% CI = 1.8% [pre-defined non-inferiority margin was 2.0%]).

Pharmacodynamic Effects of Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease: Results of the SWAP (Switching Antiplatelet Therapy)-4 Study

Circulation

Pharmacodynamic study (n=80) reported that de-escalation from ticagrelor to clopidogrel therapy is associated with an increase in platelet reactivity suggestive of a drug–drug interaction. A 600mg loading dose of clopidogrel is proposed except in patients who are bleeding.

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

Association of Varicose Veins With Incident Venous Thromboembolism and Peripheral Artery Disease

Journal of the American Medical Association

Retrospective Taiwanese study (n=212 984 varicose veins [VVs];212 984 controls) found significantly increased risk of incident DVT among adults with VVs (6.55 vs 1.23 per 1000 person-years; HR 5.30; 95% CI, 5.05-5.56). Findings for PE and peripheral artery disease are less clear.

Meta-Analysis of Genotype-Guided Versus Standard Dosing of Vitamin K Antagonists

American Journal of Cardiology

Review of 20 RCTs (total n=5,980) found a greater improvement in time in therapeutic range for genotype guided vs standard treatment (difference 3.41%, p=0.01). There were also reductions in major and all bleeding events, but no difference for INR >4 or serious adverse events.

Oral Anticoagulation in Very Elderly Patients with Atrial Fibrillation - A Nationwide Cohort Study

Circulation

Taiwanese cohort study in those ≥90 years (11, 064 with AF vs 14,658 controls) found that warfarin was associated with a lower risk of stroke vs no treatment (3.83 vs 5.75% per year, HR 0.69, 95% CI 0.49 to 0.96). Warfarin was associated with a positive net clinical benefit.

Market Authorisation Application submitted in EU and USE for turoctocog alfa pegol for haemophilia

PharmaTimes

Turoctocog alfa pegol is an extended half-life factor VIII treatment currently under investigation. Data from the pathfinder clinical trial programme form the evidence base for the submission.

Emicizumab approved for use in EU for prevention of bleeding in haemophilia A

PharmaTimes

This bispecific monoclonal antibody simultaneously binds factor IXa & factor X, exerting the same function as factor VIII but not expected to be susceptible to neutralising antibodies. It has been approved for use on the basis of the HAVEN trial programme.

Anticoagulants, including non-vitamin K antagonist oral anticoagulants (NOACs): Key therapeutic topic [KTT16]

National Institute for Health and Care Excellence

This document summarises the evidence-base on anticoagulants, including non-vitamin K antagonist oral anticoagulants (NOACs). It is a key therapeutic topic which has been identified to support medicines optimisation. It is not formal NICE guidance.

Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves

European Heart Journal

Analysis of 137 mechanical heart valve patients reports restarting therapeutic anticoagulation (TA) within 2 weeks was associated with increased haemorrhagic complications v no-TA (26% v 6%, P < 0.01); however, a non-significant decrease in thromboembolic complications was noted.

Antithrombotic therapy and body mass: an expert position paper of the ESC Working Group on Thrombosis

European Heart Journal

Consensus paper addresses issue of whether modified antithrombotic management strategies are required for patients at extremes of body weight. More focus is given to obesity due to higher prevalence in cardiovascular disease and complexities with pharmacology and pathophysiology.

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