Revised SPC: Pradaxa (dabigatran etexilate mesilate) hard capsules – all strengths

electronic Medicines compendium
SPC updated to include warning of anticoagulant-related nephropathy in patients with predisposing risk factors under bleeding reactions section.

Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis

Journal of the American Medical Association
Review of 4 RCTs (1668 saphenous vein grafts) found ticagrelor based dual antiplatelet therapy (DAPT) reduced graft failure rate per graft vs aspirin (11.2% vs 20%, OR 0.51, 95%CI 0.35-0.74) but increased BARC type 2, 3, or 5 bleeding rate (22.1% vs 8.7%, 2.98, 1.99-4.47).

Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial

Journal of the American Medical Association
RCT (n=948) found tirofiban before endovascular thrombectomy for treatment of large vessel occlusion acute ischaemic stroke did not improve disability severity at 90 days (median modified Rankin Scale score = 3 for both arms, OR 1.08, 95%CI 0.86-1.36).

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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Efficacy and Safety of Intensified Versus Standard Prophylactic Anticoagulation Therapy in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

Open Forum Infectious Diseases
Review (11 RCTs; n = 5873) found intensified anticoagulation had no effect on mortality up to 45 days among hospitalized adults with COVID-19 (RR 0.93; 95% CI 0.79–1.10) and is linked to increased bleeding risk (1.73; 1.17–2.56) vs prophylactic anticoagulation.

The Effect of Heparin and Its Preparations on Disseminated Intravascular Coagulation Mortality and Hospitalization: A Systematic Review

International Journal of Clinical Practice
Review (8 studies – 6 RCTs and 2 retrospective reviews; n=950) found a significant effect of heparin on mortality was reported in 4 of the studies. Authors conclude heparin could be effective if used in the earlier stages of this condition.

Shortage of alteplase and tenecteplase injections

NHS England
NPSA alert warns of supply constraints facing alteplase for remainder of 2022 and tenecteplase going out of stock again in coming months. Action plan for providers includes conserving alteplase for acute ischaemic stroke. Update on stock of other thrombolytics is also provided.

Protective effect of proton pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: A systematic review and meta-analysis

British Journal of Clinical Pharmacology
Review (10 studies, n=1,970,931) found PPI co-therapy linked to lower odds of total (OR 0.67; 95% CI 0.62-0.74) and major (0.68; 0.63-0.75) GI bleeding. For all kinds of oral anticoagulant, except for edoxaban, PPI cotreatment was related to 24–44%.lower odds of GI bleeding.

Great Debate: Triple antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting should be limited to 1 week

European Heart Journal
In this short review the author discusses recent evidence and the pros and cons of standardising to a default position of using a one week course of triple antithrombotic therapy after stenting in patients with atrial fibrillation or ACS.

Potent antithrombotic treatments in Asian vs. non-Asian patients

European Heart Journal
In this editorial a subgroup analysis of the COMPASS study which compared the risk of bleeding events in Asian vs. non-Asian patients exposed to rivaroxaban plus antiplatelet therapy is discussed. Overall the authors showed similarity in rates of major bleeds (2.72% vs 2.58%).

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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Association of Antisecretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis

American Journal of Medicine
Review (6 observational studies, 1 RCT) found PPIs reduce upper GI bleeding (RR 0.67; 95% CI, 0.61-0.74) with benefit appearing to be most clearcut and substantial in patients with elevated risk of upper GI bleeding (e.g. NSAID or aspirin use, elevated bleeding risk score).

Edoxaban switching scheme: worth the risks?

Pharmaceutical Journal
At end of 2021, NHSE&I confirmed details of national scheme to switch thousands of patients to edoxaban. Article notes switching anticoagulants can be particularly complex and there is speculation patients will need to be switched again in future with advent of generic apixaban.

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

Effectiveness and Safety of Intracranial Events associated with the use of Direct Oral Anticoagulants for Atrial Fibrillation: A Systematic Review and Meta-analysis of 92 Studies

British Journal of Clinical Pharmacology
Analysis of 92 studies with 107 comparisons found significant differences in the risk of ischemic stroke, thromboembolism/stroke, and intracranial haemorrhage associated with individual DOACs compared to other DOACs and Vitamin K antagonists.

Phase 1–2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B

New England Journal of Medicine
Study (n=10) reports sustained factor IX levels in normal range with low doses of FLT180a, a liver-directed adeno-associated virus gene therapy in 9 patients with haemophilia B (median follow 27.2 months) but immunosuppression with glucocorticoids with/without tacrolimus needed.

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

Intranasal Topical Application of Tranexamic Acid in Atraumatic Anterior Epistaxis: A Double-Blind Randomized Clinical Trial

Annals of Emergency Medicine
RCT (n=240) found addition of tranexamic acid to controlled therapy of phenylephrine & lidocaine was linked to a lower rate of need for anterior nasal packing (50% vs 64.2%; OR 0.56; 95% CI 0.33-0.94), stay in A+E for >2hrs (9.2% vs 20.8%) & rebleeding in 24hrs (15% vs 30%).

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

Anticoagulants for thrombosis prophylaxis in acutely ill patients admitted to hospital: systematic review and network meta-analysis

British Medical Journal
Review (44 RCTs;n=90 ,095) concluded overall, intermediate dose low-molecular-weight heparin was most likely to reduce symptomatic venous thromboembolism and intermediate dose unfractionated heparin and direct oral anticoagulants most likely to increase risk of major 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:

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Rivaroxaban and aspirin vs. aspirin alone in Asian compared with non-Asian patients with chronic coronary artery disease or peripheral arterial disease: the COMPASS trial

European Heart Journal
Analysis found rivaroxaban + aspirin vs aspirin produces similar effects for major adverse cardiovascular events, major bleeding and net clinical outcome but is associated with higher rates of intracranial haemorrhage in Asians.

2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

The Lancet Oncology
Key recommendations include low-molecular-weight heparins for initial (first 10 days) & maintenance treatment of cancer-associated thrombosis or DOACs in patients who are not at high risk of GI or genitourinary bleeding, providing no strong drug interactions or absorption issues.

Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial

The Lancet
RCT (n=1600) suggests single bolus of IV tenecteplase (0.25 mg/kg) is a reasonable alternative to alteplase bolus followed by infusion (36·9% vs. 34·8%, respectively, had modified Rankin Scale score of 0–1 at 90–120 days meeting prespecified non-inferiority threshold).

Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial

The Lancet Haematology
RCT (n=472) found thromboprophylaxis with enoxaparin 40 mg once daily for 14 days does not reduce early hospitalisations & deaths among outpatients with symptomatic COVID-19 versus standard of care (no thromboprophylaxis) and was terminated early due to futility of the treatment.

Thromboprophylactic low-molecular-weight heparin versus standard of care in unvaccinated, at-risk outpatients with COVID-19 (ETHIC): an open-label, multicentre, randomised, controlled, phase 3b trial

The Lancet Haematology
Study terminated early due to slow enrolment & lower-than-expected event rate (n=219) found prophylaxis with low-molecular-weight heparin had no benefit for at-risk outpatients with COVID-19 vs. standard-of-care (all cause mortality & hospitalisation at 21 days =11% each group).

Prescribing direct-acting oral anticoagulants – mind the evidence gap

British Journal of Clinical Pharmacology
Review notes prescribers may not be aware of the under representation of patient populations commonly encountered in clinical practice within the trials supporting approval of DOACs and highlights the gaps in licensing evidence using 4 clinical vignettes.

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

Venous Thromboembolism Prophylaxis in COVID-19: Making Sense of the Evidence

Annals of Internal Medicine
US article discusses evidence regarding VTE prevention in patients hospitalised with Covid-19, the potential reasons behind the differing outcomes between moderately ill and critically ill patients, and makes suggestions on choice of VTE prophylaxis strategy in these patients.

Rivaroxaban 2.5 mg Twice Daily Plus Aspirin Reduces Venous Thromboembolism in Patients With Chronic Atherosclerosis

Circulation
Secondary analysis of the COMPASS trial (27,395) and data review from the VOYAGER PAD study found the vascular benefits of adding rivaroxaban 2.5mg twice daily to aspirin were consistent across age, cancer status number of vascular beds involved and renal function.

Time Course for Benefit and Risk With Ticagrelor and Aspirin in Individuals With Acute Ischemic Stroke or Transient Ischemic Attack Who Carry CYP2C19 Loss-of-Function Alleles: A Secondary Analysis of the CHANCE-2 Randomized Clinical Trial

JAMA Neurology
Analysis of 6,412 patients who carry the CYP2C19 loss of function alleles in RCT comparing ticagrelor to clopidogrel (both with aspirin) found a reduction of major ischaemic events with ticagrelor in the first week, which was attenuated in weeks 2 and 3.

Subclinical Leaflet Thrombosis and Anticoagulation After Transcatheter Aortic Valve Replacement: A Review

JAMA Cardiology
This narrative review discusses several studies that have investigated the role for oral anticoagulation in patients after transcatheter aortic valve replacement, with a focus on the issue of subclinical leaflet thrombosis.

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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Rivaroxaban Monotherapy vs Combination Therapy With Antiplatelets on Total Thrombotic and Bleeding Events in Atrial Fibrillation With Stable Coronary Artery Disease: A Post Hoc Secondary Analysis of the AFIRE Trial

JAMA Cardiology
Analysis (n=2215) found rivaroxaban monotherapy linked to 38% lower risk of total CV & bleeding events, than combination anticoagulant & antiplatelet therapy (HR 0.62; 95% CI, 0.48-0.80; p < 0.001) and mortality risk after a bleeding event was higher than after a thrombotic event.

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

Efficacy and Safety Considerations With Dose-Reduced Direct Oral Anticoagulants: A Review

JAMA Cardiology
Review of 72 RCTs found efficacy & safety results for dose-adjusted DOACs in large RCTs of AF were similar to those for full-dose DOACs. No studies investigating dose adjusted DOACs in acute VTE, but authors suggest low-intensity DOACs are appropriate for approved indications.

Antithrombotic Therapy for Venous Thromboembolism (second update of the chest guideline and expert panel report)

Journal of the American Medical Association
This US guidance recommends outpatient treatment for patients with low-risk pulmonary embolism, DOAC treatment for patients in the acute VTE 3 month treatment phase & oral factor Xa inhibitors for acute VTE treatment in cancer patients in initial and extended treatment phases.

Incidence of nonvalvular atrial fibrillation and oral anticoagulant prescribing in England, 2009 to 2019: A cohort study

PLOS Medicine
Study (between 2009 & 2019; n=12,517,191) using UK CPRD database noted incidence of non valvular AF increased between 2009 and 2015, before plateauing, and underprescribing of oral anticoagulants was liked to a range of comorbidities, ethnicity, and socioeconomic factors.

Factors associated with non-adherence to the use of coumarin derivatives or direct oral anticoagulants: a systematic review of observational studies

British Journal of Clinical Pharmacology
Review (9 studies) found factors linked to non-adherence were heterogeneous; few showed consistent results. Variables reported as risk factors were male sex, hospitalization, Charlson score & bleeding. White race, CHA2DS2VASc (2-9) & polypharmacy reported as protective factors.

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