Impact of P-glycoprotein and/or CYP3A4-interacting drugs on effectiveness and safety of NOACs in patients with atrial fibrillation: a meta-analysis

British Journal of Clinical Pharmacology
Review (15 studies) found in AF patients treated with NOACs, concomitant use of P-gp/CYP3A4 inhibitors was associated with higher risk of major bleeding (RR 1.10, 95% CI 1.01-1.19) and all-cause mortality (1.14, 95% CI 1.05-1.23); authors recommend close monitoring.

 

Risk factors associated with venous and arterial neonatal thrombosis in the intensive care unit: a multicentre case-control study

The Lancet Haematology
Study of 118,952 admissions to 31 neonatal intensive care units found bloodstream infection (OR 2.07), maternal diabetes (1.62), abdominal surgery (1.36) and thrombocytopenia (2.44) were the most significant risk factors for venous thrombosis (p<0.0001 for all).

 

Revised SPC: Clexane (enoxaparin)- all presentations

electronic Medicines compendium
SPC updated to warn acute generalised exanthematous pustulosis reported (unknown frequency); patients should be advised of signs/symptoms & monitored for skin reactions, enoxaparin should be withdrawn immediately & alternative treatment considered (as appropriate), if this occurs.

 

Association of Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase

Journal of the American Medical Association
Retrospective study (n=163,038) found NOAC use within past 7 days was not associated with increased risk of intracranial haemorrhage among patients with acute ischaemic stroke treated with alteplase (3.7% vs 3.2% in those not taking NOACs; adjusted OR 0.88 [95% CI 0.70 to 1.10]).

 

Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial

Journal of the American Medical Association
Phase 2b trial (n=121) found use of intra-arterial alteplase following thrombectomy resulted in a greater likelihood of excellent neurological outcome (modified Rankin Scale score of 0 or 1) than placebo at 90 days (59.0% vs 40.4%; P=0.047); these findings require confirmation.

 

US FDA grants Fast Track Designation for asundexian for the secondary prevention in patients with non-cardioembolic ischaemic stroke

Biospace Inc.
Asundexian is an oral inhibitor of Factor Eleven (FXIa) that is also being developed for atrial fibrillation and recent myocardial infarction. It is currently in Phase II clinical trials in all three conditions either as monotherapy or in combination with 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

Bivalirudin versus heparin in pediatric and adult patients on extracorporeal membrane oxygenation: A meta-analysis.

British Journal of Clinical Pharmacology
Analysis (9 studies, n=994) found bivalirudin linked to lower risks of major bleeding (risk ratio 0.32;95% CI 0.22-0.49), ECMO in-circuit thrombosis (0.57;0.43-0.74), stroke (0.52;0.29-0.95), in-hospital mortality (0.82;0.69-0.99) & higher rates of survival to ECMO decannulation.

 

Anticoagulants for acute ischaemic stroke

Cochrane Database of Systematic Reviews
In updated review (28 trials [4 new];n=24,025), conclusions remain consistent, in that people who have early anticoagulation post acute ischaemic stroke do not show any net short‐ or long‐term benefit, with reduction in recurrent stroke, DVT & PE offset by increased 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

 

Heparin use in acute coronary syndromes and cardiovascular interventions: habit or evidence based?

European Heart Journal
Viewpoint argues certain applications of unfractionated heparin remain guided by historical experience rather than robust clinical trials, and that further studies are required to evaluate indication, dosing, and monitoring required for use in routine cardiovascular procedures.

 

Clotting factor concentrates for preventing bleeding and bleeding‐related complications in previously treated individuals with haemophilia A or B

Cochrane Database of Systematic Reviews
Review (10 RCTs; n=608) concludes prophylaxis may reduce bleeding frequency and improve joint function, pain and quality of life vs on-demand treatment, even though this does not translate into a detectable improvement of articular damage when assessed by MRI.

 

Antithrombotic therapy for ambulatory patients with multiple myeloma receiving immunomodulatory agents

Cochrane Database of Systematic Reviews
This living systematic review (4 RCTs, n=1042) found that the certainty of the available evidence for the comparative effects of aspirin, vitamin K antagonist, low molecular weight heparain, and DOAC on all‐cause mortality, DVT, PE, or bleeding was either low or very low.

 

 

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

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

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