DTB select: DOAC drug interactions and risk of major bleeding

Drug and Therapeutics Bulletin
Summary and context are provided for a UK case–control study which found that use of antiplatelet drugs and SSRIs with DOACs was associated with an increased risk of major bleeds requiring hospital admission.

Warfarin dosing algorithms: A systematic review

British Journal of Clinical Pharmacology
Review (266 articles) found most algorithms have been developed in Asian and White populations and may not be applicable to under‐served populations. Few algorithms had been externally validated, assessed for clinical utility, and/or have a low risk of bias.

DTB select: Tranexamic acid should be avoided for acute gastrointestinal bleeds

Drug and Therapeutics Bulletin
Summary and context is provided on the HALT-IT trial which involved 12 000 people being treated for acute gastrointestinal bleeding, and found tranexamic acid had no effect on risk of death from bleeding but increased the risk of thromboembolism and seizures.

Association of risk factors and bleeding complications in Asian patients taking edoxaban

British Journal of Clinical Pharmacology
Trial (n=346) found weight ≤60 kg & presence of cancers could affect bleeding complications, which occurred despite proper edoxaban treatment in Asian patients. Authors suggest possibility of using more strict dosage guideline could be considered in patients of Asian ethnicities.

Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial

The Lancet Neurology
RCT (n=173 per protocol) did not show that aspirin was non-inferior to vitamin K antagonists (VKAs) in treatment of cervical artery dissection (primary endpoint in 21 [23%] of 91 patients on aspirin vs. 12 [15%] of 82 on VKA (absolute difference 8%, non-inferiority p=0.55).

P2Y12 inhibitor monotherapy after coronary stenting according to type of P2Y12 inhibitor

Heart
RCT (n=2993) found that 3-month dual antiplatelet therapy (DAPT) followed by clopidogrel monotherapy provided similar rates of a composite endpoint (all-cause death, myocardial infarction or stroke at 12 months) vs 12 months DAPT (3.0% for both, HR 1.02).

Incidence and predictors of stroke in patients with rheumatic heart disease

Heart
Cohort study (n=515) notes despite wide use of oral anticoagulants, stroke (SK) remains frequent in this population (1.47 SKs per 100 patient-years), with age, AF & prior SK predictors of long-term SK; more aggressive monitoring of anticoagulation may be warranted in recurrent SK.

Drug‐drug Interactions with Warfarin: A Systematic Review and Meta‐analysis

British Journal of Clinical Pharmacology
Analysis of 72 studies (11 RCTs; total n=3,735,775) found addition of antiplatelets (OR 1.74), antimicrobials (1.63), NSAIDs (1.83) SSRIs (1.62), mirtazapine (1.75) and loop diuretics (1.92) to warfarin was associated with increased risk of clinically relevant bleeding.

Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis

Thorax
Analysis (102 studies; n=64,503) found the frequency of COVID-19-related VTE was 14.7%; prevalence was higher in ICU (23.2% v 9.0%; P<0.0001). The frequency rate of overall arterial thromboembolic events was 3.9%; subgroup analyses failed to explain heterogeneity.

Antithrombotic therapy in diabetes: which, when, and for how long?

European Heart Journal
This review provides an up-to-date guide for antithrombotic management of individuals with diabetes mellitus and highlights gaps in knowledge that represent areas for future research, aiming to improve clinical outcome in this high-risk population.

HElping Alleviate the Longer-term consequences of COVID-19 (HEAL-COVID): national platform trial

HEAL-COVID
This study, which will enrol patients admitted to hospital with Covid-19 who are about to be discharged, will investigate whether apixaban (for 2 weeks) or atorvastatin (for 12 months) could prevent or reduce long-term outcomes for patients with Covid-19.

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

Prasugrel versus ticagrelor in patients with myocardial infarction undergoing percutaneous coronary intervention

Heart
During 1-year follow-up of 37,990 Swedish patients, prasugrel and ticagrelor were associated with similar efficacy (risk of major adverse cardiac and cerebrovascular events: HR 1.03; 95% CI 0.86 to 1.24) and bleeding risk (2.5% vs 3.2%, adjusted HR 0.92, 95% CI 0.69 to 1.22).

Administering Thrombolysis for Acute Ischemic Stroke in Patients Taking Direct Oral Anticoagulants: To Treat or How to Treat

JAMA Neurology
The authors discuss potential approaches and recommend a tailored approach to select patients taking DOAC with acute ischaemic stroke for thrombolysis by combining clinical and imaging information with anticoagulant activity and use of specific reversal agents only if necessary.

International Society on Thrombosis and Haemostasis (ISTH) statement on the AstraZeneca COVID-19 vaccine and thrombosis

The International Society on Thrombosis and Haemostasis
The ISTH recommends that all eligible adults continue to receive COVID-19 vaccinations, despite the recent decisions by some countries to at least temporarily suspend the use of the AstraZeneca vaccine due to reports of thrombosis.

Diagnosis and Management of Transient Ischemic Attack and Acute Ischemic Stroke: A Review

Journal of the American Medical Association
This review provides an update on management of transient ischaemic attack and acute ischaemic stroke, emphasising advances in use of dual antiplatelet therapy and fibrinolysis vs mechanical thrombectomy for secondary and tertiary prevention.

Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

The Lancet Neurology
Analysis of 38 hospital-based prospective cohort studies from 18 countries (n=31,550) suggests MICON risk scores, incorporating clinical variables & cerebral microbleeds, offer predictive value for long-term risks of intracranial haemorrhage & ischaemic stroke in this population.

MHRA confirms people should continue to receive COVID-19 vaccine AstraZeneca

Medicines and Healthcare products Regulatory Agency
Following rigorous scientific review of all available data, MHRA said available evidence does not suggest venous thromboembolism is caused by COVID-19 Vaccine AstraZeneca and benefits of the vaccines against COVID-19 continue to outweigh any risks.

COVID-19 Vaccine AstraZeneca: benefits still outweigh the risks despite possible link to rare blood clots with low blood platelets

European Medicines Agency
The European PRAC has concluded its preliminary review of a signal of blood clots in people vaccinated with COVID-19 Vaccine AstraZeneca and confirmed its benefits in combating the still widespread threat of COVID-19 continue to outweigh the risk of side effects.

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit - The INSPIRATION Randomized Clinical Trial

Journal of the American Medical Association
This study in Iran (n=600; 562 in primary analysis) found no difference between routine use of intermediate dose (enoxaparin 1mg/kg daily) and standard prophylactic anticoagulation (enoxaparin 40mg daily) in terms of the composite primary endpoint (45.7% v 44.1%).

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

Enoxaparin is associated with lower rates of mortality than unfractionated Heparin in hospitalized COVID-19 patients

EClinical Medicine
Analysis of 607 of 1113 records in Mayo Clinic Electronic Health Record database found that COVID-19 patients administered unfractionated heparin but not enoxaparin had higher rates of 28-day mortality (risk ratio: 4.3; 95% CI; 1.8-10.2).

Epistaxis

New England Journal of Medicine
Review covers vasoconstrictors, tranexamic acid, cauterisation, anterior nasal packing, resorbable/non-resorbable packing, salvage bleeding control, posterior packing, ligation & endovascular embolisation, patients on anticoagulant and antiplatelets, and patient education.

European PRAC starts review of signal of thrombocytopenia with Pfizer/BioNTech, AstraZeneca and Moderna COVID-19 vaccines

European Medicines Agency
Several cases of immune thrombocytopenia, an adverse event of special interest, were reported in the EudraVigilance database. The PRAC will carry out an in-depth review of all the available data for these three vaccines, to decide if a causal relationship is confirmed or not.

World Health Organisation’s global advisory committee on vaccine safety reviewing AstraZeneca Covid-19 vaccine

Reuters Health
A World Health Organization expert advisory committee is currently looking at AstraZeneca's COVID-19 vaccine after some countries suspended its use, following reports of the formation of blood clots in some people who have been vaccinated.

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

Thrombolytic strategies versus standard anticoagulation for acute deep vein thrombosis of the lower limb

Cochrane Database of Systematic Reviews
Review (19 RCTs; n=1943) found more frequent complete clot lysis after thrombolysis (TS) with/without additional clot removal strategies and post‐thrombotic syndrome incidence was slightly reduced. Systemically administered and catheter‐directed TS have similar effectiveness.

Comparing risk of major bleeding between users of different oral anticoagulants in patients with nonvalvular atrial fibrillation

British Journal of Clinical Pharmacology
Analysis of 4 cohorts (UK, Spain, Germany, Denmark,n = 251,719) found reduction in bleeding risk for DOACs doesn't resemble reductions found in trials. This could be at least partially attributable to nonadherence and limited external validity of trials, reflecting real‐life settings.

Beyond dexamethasone, emerging immuno‐thrombotic therapies for COVID‐19

British Journal of Clinical Pharmacology
Understanding mechanisms underpinning hyperinflammation & coagulopathy is essential to formulating rationale therapeutic approaches beyond use of dexamethasone. Article reviews pathophysiology thought to underlie COVID‐19 with clinical correlates and therapies being investigated.

Patterns and factors influencing oral anticoagulant prescription in people with atrial fibrillation and dementia: Results from UK primary care

British Journal of Clinical Pharmacology
UK study found oral anticoagulant (OAC) prescriptions among patients with AF and dementia/cognitive impairment increased by 39.8% between 2000 and 2015. Characteristics related to frailty (e.g. history of falls, polypharmacy) were associated with lower odds of OAC prescription.

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