Direct Oral Anticoagulants versus Warfarin in Patients with Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials with Interaction Testing by Age and Sex

Circulation
Analysis (n=71,683) found standard-dose DOACs linked to significantly lower risk of stroke/systemic embolism (3.01 v 3.69%; HR 0.81, 95% CI 0.74-0.89), death (7.76 v 8.42%; 0.92, 0.87-0.97) and intracranial bleeding (0.63 v 1.40%; 0.45, 0.37-0.56) vs. warfarin in this population.

Antiplatelet therapy in cardiovascular disease: current status and future directions

British Journal of Clinical Pharmacology
Article reviews evidence for aspirin and P2Y12 inhibitors in different clinical situations, the place of anticoagulation on top of antiplatelet therapy in atherosclerotic diseases, and considers whether personalised approaches may be useful for maximising benefit/risk ratio.

Revised SPC: Pradaxa (dabigatran) 75mg, 110mg and 150 mg hard capsules

electronic Medicines compendium
Dabigatran is now additionally licensed for the treatment of VTE and prevention of recurrent VTE in paediatric patients from birth to less than 18 years of age.

Effect of Anticoagulant Therapy for 6 Weeks vs 3 Months on Recurrence and Bleeding Events in Patients Younger Than 21 Years of Age With Provoked Venous Thromboembolism. The Kids-DOTT Randomized Clinical Trial

Journal of the American Medical Association
In this RCT involving 417 patients it was shown that symptomatic recurrent VT occurred in 0.66% vs 0.7% of 6 week vs 3 month course recipients and clinically relevant bleeding in 0.65% vs 0.7% respectively thereby meeting the defined criteria for clinical non-inferiority.

Anticoagulant Treatment Regimens in Patients with Covid-19: A Meta-Analysis

Clinical Pharmacology and Therapeutics
Review (10 RCTs; n=5753) found similar risk of death & net adverse clinical events (death, thromboembolic events, major bleeding) between higher-dose (HD including therapeutic & intermediate-dose) anticoagulation & prophylactic-dose, thus not supporting routine use of HD regimens.

Pradaxa (dabigatran etexilate): Prescriber guide for paediatric use for the treatment of venous thromboembolic events (VTE) and prevention of recurrent VTE

Boehringer Ingelheim
Guide discusses the paediatric indication, contraindications, dosing, populations at higher bleeding risk, perioperative management, coagulation tests, overdose, management of complications, special guidance for use of the oral solution, and the patient alert card and counselling.

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

Dabigatran etexilate (Pradaxa®) recommended for use within NHS Wales for venous thromboembolism (VTE) treatment and prevention in paediatric patients

All Wales Medicines Strategy Group
Dabigatran etexilate (Pradaxa®) hard capsules are recommended as an option for the treatment of venous thromboembolic events (VTE) and prevention of recurrent VTE in paediatric patients from 8 years to less than 18 years of age.

Rivaroxaban (Xarelto®) recommended for use within NHS Wales for venous thromboembolism (VTE) treatment and prevention in paediatric patients

All Wales Medicines Strategy Group
Rivaroxaban (Xarelto®) granules for oral suspension and film-coated tablets are recommended for the treatment of VTE and prevention of VTE recurrence in term neonates, infants and toddlers, children, and adolescents after ≥5 days of initial parenteral anticoagulation treatment.

Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups: A Systematic Review and Individual-Patient Data Meta-analysis

Annals of Internal Medicine
Review (16 studies;n=20,553) found all strategies showed acceptable safety with pretest probability–dependent D-dimer thresholds(DDTs) having both highest efficiency (EF) & highest predicted failure rate. In terms of EF, individual-patient data meta-analysis supports adapted DDTs.

Assessment of adherence, treatment satisfaction and knowledge of direct oral anticoagulants in atrial fibrillation patients

British Journal of Clinical Pharmacology
Longitudinal study (n=164) found adherence was suboptimal in 40.6% patients after 3 months and 42.6% after 6 months. Treatment satisfaction & knowledge were not associated with DOAC adherence over 6 month period. Patient education & follow-up may address identified knowledge gaps.

Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61 898 patients from 15 randomized trials

European Heart Journal
Analysis (15 RCTs; n=61,898) found guided approach (platelet function or genetic testing) was the only strategy associated with reduced major adverse cardiovascular events (IRR 0.80, 95% CI 0.65–0.98) without any significant trade-off in all bleeding (IRR 1.22, 95% CI 0.96–1.55).

Association of Psoriasis With Incident Venous Thromboembolism and Peripheral Vascular Disease: A Systematic Review and Meta-analysis

JAMA Dermatology
Meta-analysis (13 cohort studies;n=12,435,982) noted increased risk for VTE (pooled HR 1.26;95% CI, 1.08-1.48) & PVD (1.27;1.16-1.40) among patients with psoriasis. This suggests need to identify & treat risk factors & caution with use of hormone-related therapies in this group.

Comparison of Ticagrelor vs Clopidogrel in Addition to Aspirin in Patients With Minor Ischemic Stroke and Transient Ischemic Attack: A Network Meta-analysis

JAMA Neurology
Review (5 RCTs; n=22,098) found both clopidogrel and aspirin (HR 0.74; 95% CrI 0.65-0.84) and ticagrelor & aspirin (0.79; 0.68-0.91) were superior to aspirin alone in the prevention of recurrent stroke & death, with no statistically significant difference between the two regimens.

Risk for Recurrent Venous Thromboembolism and Bleeding With Apixaban Compared With Rivaroxaban: An Analysis of Real-World Data

Annals of Internal Medicine
US retrospective study of adults with VTE found new users of apixaban had lower rates of recurrent VTE (HR 0.77; 95% CI 0.69 to 0.87]) and gastrointestinal and intracranial bleeding (0.60; 0.53 to 0.69) than new users of rivaroxaban.

Optimal follow-up after acute pulmonary embolism

European Heart Journal
This European position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism, proposing a holistic approach considering the whole spectrum of serious adverse events that patients may encounter in the short and long run.

How Strong Is the Evidence Supporting Thromboprophylaxis in Surgical Oncology?

Journal of Clinical Oncology
Article argues there are critical weaknesses to RCTs of pharmacologic thromboprophylaxis for patients undergoing cancer surgery underpinning guidelines, including unexplored potential for heterogeneity in endpoints, unclear effect on survival, and lack of supportive care outcomes.

Sex-influence on the time in therapeutic range (TTR) during oral anticoagulation with coumarin derivatives: Systematic review and meta-analysis

British Journal of Clinical Pharmacology
Review (22 studies; n=183,612) found link between female sex & worse oral anticoagulation control (of 15 studies analysed using TTR as binary variable: OR = 0.87; 95% CI = 0.78-0.96; p =0 .006). Authors call for further studies investigating sex-related factors influencing control.

Respiratory tract infection and risk of bleeding in oral anticoagulant users: self-controlled case series

British Medical Journal
Study (n=1208) found >2-fold increase in risk of major & clinically relevant non-major bleeding during 0-14 days after untreated respiratory tract infection for which no antibiotics were prescribed, highlighting need for further investigation into potential risks & mitigation.

FDA approves two new indications for Xarelto (rivaroxaban) in paediatric patients

Biospace Inc.
In the US rivaroxaban is now licensed for treatment of venous thromboembolism (VTE) and recurrent VTE prevention in patients from birth to <18yrs post 5 days parenteral anticoagulation and thromboprophylaxis aged ≥2yrs with congenital heart disease & undergone Fontan procedure.

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

Mechanism suggested for development of rare blood clots with AstraZeneca covid 19 vaccine

Science Advances
This rare syndrome resembling heparin-induced thrombocytopenia (HIT), has been observed with ChAdOx1 (AZ) vaccine. Computational simulation study showed 3 adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to PF4, a protein implicated in pathogenesis of HIT.

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

Milvexian for the Prevention of Venous Thromboembolism

New England Journal of Medicine
In this Phase II study of patients undergoing knee arthroplasty (n=1242), the oral factor XIa inhibitor milvexian was associated with venous thromboembolism in 7% to 25% depending on the dose used, as compared to 21% taking enoxaparin 40mg once daily.

Comparison of the HAS-BLED versus ORBIT Scores in Predicting Major Bleeding Among Asians Receiving the Direct-Acting Oral Anticoagulants

British Journal of Clinical Pharmacology
Thai retrospective study (n=961) found HAS-BLED and ORBIT scores showed a similar moderate predictive performance on bleeding using the C-statistic test, with no significant difference between scores (0.65 vs 0.64, p=0.62).

NHS England strikes new agreement to expand use of DOACs for atrial fibrillation

NHS England
NHS England are intending to scale up the use of DOACs with as many as 610,000 more patients expected to benefit over the next three years. A procurement deal on DOACs has been reached to help expand access by making treatment more affordable.

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

Tranexamic acid in gastrointestinal bleeding: A systematic review and meta-analysis

Critical Care Medicine
Systematic review (12 RCT's) found extended-use high-dose IV tranexamic acid did not improve mortality or bleeding risk & increases adverse events (DVT, PE & seizures). Low-dose/enteral tranexamic acid reduced risk of rebleeding and need for surgery.

Comparison of clinical outcomes using activated partial thromboplastin time versus antifactor-Xa for monitoring therapeutic unfractionated heparin: A systematic review and meta-analysis

Thrombosis Research
This systematic review (n=6677, 10 studies) found pooled data suggests no difference in bleeding or thrombosis rates when comparing activated partial thromboplastin time and antifactor Xa heparin assay for monitoring of therapeutic unfractionated heparin.

A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke

New England Journal of Medicine
RCT (n=539) found endovascular treatment (EVT) was neither superior nor noninferior to IV alteplase followed by EVT with regard to disability outcome at 90 days after stroke (OR 0.84; 95% CI, 0.62-1.15) & incidence of symptomatic intracerebral haemorrhage was similar (5.9 v 5.3%).

Vaccine-induced immune thrombotic thrombocytopenia (VITT)

The Lancet Haematology
Viewpoint discusses epidemiology, pathophysiology, and optimal diagnostic and therapeutic management of VITT. Presentation of possible VITT should raise prompt testing for anti-PF4 antibodies and initiation of treatment with IV immunoglobulin and non-heparin anticoagulation.

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

Oral Anticoagulant Use in Patients with Morbid Obesity: A Systematic Review and Meta-Analysis

Journal of Thrombosis and Haemastasis
Review of 3 RCTs and 18 observational studies in morbidly obese found those on DOACs had lower rates of recurrent VTE than those on vitamin K antagonists (3.83 vs 6.81 per 100 person years). Rates of stroke and systemic embolism and major bleeding events were similar.

Using oral anticoagulants in breastfeeding women

Specialist Pharmacy Service
Evidence summary notes thromboembolic disease management whilst breastfeeding is challenging. Warfarin is the preferred choice, but guidance on using DOACs is also provided. It notes recommendations apply to full-term and healthy infants only.

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

Left Ventricular Dysfunction Among Patients With Embolic Stroke of Undetermined Source and the Effect of Rivaroxaban vs Aspirin: A Subgroup Analysis of the NAVIGATE ESUS Randomized Clinical Trial

JAMA Neurology
Post hoc exploratory analysis (n=502) found rivaroxaban was superior to aspirin in reducing the risk of recurrent stroke or systemic embolism among NAVIGATE ESUS participants with left ventricular dysfunction (annualised primary event rates: 2.4% vs 6.5%, respectively).

Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA

New England Journal of Medicine
RCT at 202 centres in China (n=6412) found in Chinese patients with minor ischaemic stroke/TIA who were carriers of CYP2C19 loss-of-function alleles, stroke risk at 90 days was modestly lower with ticagrelor than clopidogrel (6.0 vs. 7.6%; HR 0.77; 95% CI, 0.64 to 0.94; p=0.008).

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

Safety and efficacy of different prophylactic anticoagulation dosing regimens in critically and non-critically ill patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials

European Heart Journal-Cardiovascular Pharmacotherapy
Review (7 RCTs; n=5,154) found escalated-dose prophylactic anticoagulation was associated with lower rates of VTE (2.5% vs. 4.7%; RR 0.55, 95% CI 0.41–0.74) but no benefit on other outcomes vs standard dose; and it increased risk of major bleeding (2.4% vs. 1.4%).

Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR

European Heart Journal
This pre-specified analysis of the TWILIGHT trial found withdrawal of aspirin after 3 months in those with no events reduced bleeding risk (6.3% vs. 11.4%; HR 0.53, 95% CI 0.35–0.82) without increasing ischaemic events when compared to continued aspirin and ticagrelor.

Antithrombotic Therapy in Patients Undergoing Transcatheter Interventions for Structural Heart Disease

Circulation
Review discusses current evidence on the use of antithrombotic therapy in these patients, noting the optimal regimens to adopt in each specific procedure is still unclear, and emphasizing the importance of a tailored approach.

Apixaban versus no anticoagulation after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation in the Netherlands (APACHE-AF): a randomised, open-label, phase 2 trial

The Lancet Neurology
RCT (n=101) found over median follow-up of 1.9 years, there was high subsequent annual risk of non-fatal stroke/vascular death, whether allocated to apixaban or to avoid anticoagulation (annual event rate 12·6% vs 11·9%, respectively, HR 1.05; 95% CI 0.48–2.31; p=0.90).

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

Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants: A Nationwide Propensity Score–Weighted Study

Annals of Internal Medicine
Study (n=2,157) found rates of GI bleeding were higher for rivaroxaban than apixaban (3.2 vs. 2.5 overall events per 100 person-years [HR 1.42; 95% CI 1.04 to 1.93; major bleeding HR 1.50 [1.00 to 2.24]) and dabigatran (similar estimates but including possibility of null effect).

All Wales Medicines Strategy Groups consults on draft guidance on oral anticoagulation for non-valvular atrial fibrillation

All Wales Medicines Strategy Group
This consultation presents a proposed update to the current guidance, following the publication of updated NICE guidance (NG196; published June 2021). The update includes re-positioning DOACs before vitamin K antagonists, and an amendment to the tool for assessing bleeding risk.

Would You Recommend Aspirin to This Patient for Primary Prevention of Atherosclerotic Cardiovascular Disease?

Annals of Internal Medicine
In this article, two clinicians discuss and debate current guidelines on use of aspirin for primary prevention of atherosclerotic vascular disease, the appropriate risk threshold for starting aspirin therapy, and the role of the coronary artery calcium score in decision making.

Reduction in Acute Limb Ischemia with Rivaroxaban versus Placebo in Peripheral Artery Disease after Lower Extremity Revascularization: Insights from VOYAGER PAD

Circulation
Review of VOYAGER PAD study (n=6564) found, in those with prior lower extremity revascularisation, rivaroxaban reduced acute limb ischaemia vs placebo (by 2.6% at 3 years; HR 0.67, 95%CI 0.55 to 0.82) with a benefit starting early (HR 0.45, 0.24 to 0.85 at 30 days after surgery).

Anticoagulant prescribing for atrial fibrillation and risk of incident dementia

Heart
In study of healthcare records from UK CPRD (n=39,200 of whom 1258 had dementia [DM]), use of DOAC for AF was linked to 16% reduction in DM diagnosis vs. Vit K antagonist (HR 0.84, 95% CI: 0.73-0.98) & 26% reduction in incident mild cognitive impairment (0.74, 95% CI: 0.65-0.84).

Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial

British Medical Journal
This RCT in hospitalised adults with Covid-19 and increased D-dimer levels (n=465; mean BMI 30.3 kg/m2) found therapeutic dose heparin did not reduce the risk of the primary composite endpoint (16.2% v 21.9% prophylactic dose; OR 0.69, 95% CI 0.43 to 1.10; P=0.12).

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

Temporal Association Between Episodes of Atrial Fibrillation and Risk of Ischemic Stroke

JAMA Cardiology
Cohort study (n=891) found excess stroke risk was highest within 5 days of an episode of atrial fibrillation (AF) of >5.5 hours in duration and diminished rapidly thereafter, thus supporting trials of time-delimited anticoagulation for infrequent multi-hour episodes of AF.

Revised SPC: Clexane (enoxaparin) pre-filled syringes

electronic Medicines compendium
SPC updated to note licence extension for use as extended treatment of deep vein thrombosis and pulmonary embolism and prevention of its recurrence in patients with active cancer.

Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial

JAMA Internal Medicine
In RCT (n=253), therapeutic-dose LMWH reduced major thromboembolism & death vs institutional standard heparin thromboprophylaxis (28.7 vs 41.9%;RR 0.68; 95% CI, 0.49-0.96;p= 0.03) among inpatients with very elevated D-dimer levels, with no significant difference in major bleeding.

Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial

The Lancet
RCT (n= 2697, South Korea) found unguided de-escalation antiplatelet strategy (switching from ticagrelor+aspirin [TA] to clopidogrel+aspirin) was superior to remaining on TA at preventing net adverse clinical events up to 12 months, mainly by reducing bleeding events.

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