Association of Type of Oral Anticoagulant Dispensed With Adverse Clinical Outcomes in Patients Extending Anticoagulation Therapy Beyond 90 Days After Hospitalization for Venous Thromboembolism

Journal of the American Medical Association
Cohort study (n=64,642) found a lower incidence of recurrent VTE for apixaban vs warfarin (9.8 vs 13.5/1000 person-years, HR 0.69, 95%CI 0.49-0.99), but no difference for apixaban vs rivaroxaban & rivaroxaban vs warfarin. Rates of major bleeding were similar for all treatments.

Physicians Adherence to Evidence-Based Guidelines as a Major Predictor to Anticoagulant-related Medication Errors Incidence and Severity

British Journal of Clinical Pharmacology
Study in tertiary hospital (n=116 with 2166 anticoagulant doses[ADs]) noted 44% prescribed ADs resulted in medication errors (MEs) & major predictor in increasing both MEs incidence & severity is physician adherence to evidence-based guidelines (OR 24.67; 95% CI 5.54–207;p<0.001).

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Journal of the American Medical Association
RCT (n=1,557) found antiplatelet therapy (aspirin or P2Y12 inhibitor), vs no antiplatelet therapy, had a low likelihood of improving organ support–free days (composite of in-hospital mortality and duration of ICU–based respiratory or cardiovascular support) within 21 days.

How to handle a delayed or missed dose of edoxaban in patients with non-valvular atrial fibrillation? A model-informed remedial strategy

British Journal of Clinical Pharmacology
Simulation study exploring remedial strategies for edoxaban non-adherence recommends the missed dose can be taken immediately if the delay time is ≤11 h. A half dose followed by regular dosing is recommended for 12-19 h delay, and a full followed by half dose for a delay >19 h.

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 aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial

The Lancet
RCT (n=663), stopped early due to safety concerns, found risk of symptomatic intracranial haemorrhage was higher in patients randomised to aspirin (14% v 7% in those not on aspirin; adjusted OR 1.95 [95% CI 1.13–3.35]) and unfractionated heparin (13% v 7%; 1.98 [1.14–3.46]).

Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome: The STOPDAPT-2 ACS Randomized Clinical Trial

JAMA Cardiology
RCT (n=4136) found effectiveness of clopidogrel monotherapy after 1 to 2 months of dual antiplatelet therapy (DAPT) is inconclusive (1-year incidence rate of primary end point of CV & bleeding events = 3.2% vs. 2.8% in 12-month DAPT group, failing to meet noninferiority criteria).

Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis of randomised trials

British Medical Journal
Review (68 RCTs; n=45 445) found DOACs & low/high dose LMWH reduced VTE vs.no active treatment (OR 0.17, 95% CI 0.07-0.41; 0.33, 0.16-0.67; 0.19; 0.07-0.54) but probably increase major bleeding (2-3 fold) to similar extent; DOACs probably prevent symptomatic VTE to greater extent.

Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study

European Heart Journal
Study (n=59,076) suggests NOACs may be linked to positive net clinical benefit, with lower stroke rate (HR 0.72; 95% CI 0.56–0.94) & no increase intracranial haemorrhage (ICH) risk vs. no treatment & similar stroke rate vs. VKAs but lower rate ICH with NOACs (HR 0.63; 0.42–0.94).

DTB Select: Risk of gastrointestinal bleeding with concomitant NOAC and glucocorticoid treatment

Drug and Therapeutics Bulletin
Summary and context are provided on a case-control study that found concomitant treatment with a NOAC and an oral glucocorticoid was associated with a modest increase in the risk of a bleeding event compared with no glucocorticoid exposure.

Evaluation of antithrombotic use and COVID-19 outcomes in a nationwide atrial fibrillation cohort

Heart
Study found pre-existing antithrombotic use associated with lower odds of Covid-related death (OR 0.92, 95%CI 0.87-0.96) and although this link may not be causal, researchers suggest it provides further incentive to improve antithrombotic coverage for eligible individuals with AF.

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

Anticoagulation for the initial treatment of venous thromboembolism in people with cancer

Cochrane Database of Systematic Reviews
Updated review including 15 RCTs (n=1615) found low molecular weight heparin is probably superior to unfractionated heparin for initial VTE treatment in cancer. Additional trials focusing on patient‐important outcomes will further inform the questions addressed in this review.

Prevalence and management of drug interactions between NSAID and antithrombotics in ambulatory care

British Journal of Clinical Pharmacology
This article discusses a prospective intervention study of 782 interactions from an older, polymedicated patient population. It found anticoagulants were involved in 16.1% of the cases and for 61% of all cases, the interacting drugs were prescribed by the same physician.

Two-year outcomes of UK patients newly diagnosed with atrial fibrillation: findings from the prospective observational cohort study GARFIELD-AF

British Journal of General Practice
Anticoagulation (AC) treatment vs no AC was linked to significantly lower all-cause mortality & risk of non-haemorrhagic stroke/ systemic embolism (aHR 0.70; 95% CI 0.53 to 0.93 & 0.39; 95% CI 0.24-0.62) and a non-significant higher risk of major bleeding (1.31;95% CI 0.77-2.24).

Comparative efficacy and safety of oral anticoagulants for the treatment of venous thromboembolism in the patients with different renal functions: a systematic review, pairwise and network meta-analysis

BMJ Open
Review (10 RCTs; n=37,298) found no significant differences in efficacy of DOACs among the three creatinine clearance subgroups, for acute or extended treatment of VTE. Aapixaban may be associated with lower bleeding risk in CrCl >80 mL/min subgroup; confirmation is needed.

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism

Cochrane Database of Systematic Reviews
Review (34 studies; n=14,931) found combining intermittent pneumatic leg compression (IPC) with pharmacological prophylaxis (PP) reduces incidence of PE & DVT vs. IPC alone (low‐certainty evidence [LCE]). Compared to PP alone, it also reduces incidence of PE(LCE) & DVT (high‐CE).

Oral antiplatelet therapy for acute ischaemic stroke

Cochrane Database of Systematic Reviews
Updated review (11 studies, n=42,226) found antiplatelet therapy with aspirin 160-300 mg daily started within 48 hours significantly decreased death & dependency, and reduced risk of early recurrent stroke without a major risk of early haemorrhagic complications.

Heparin versus citrate anticoagulation for continuous renal replacement therapy in intensive care: the RRAM observational study

National Institute for Health Research
Analysis of responses to survey from 181 NHS adult general ICUs in England, Wales (n=69,001) found change to regional citrate anticoagulation was not linked to step change in 90-day mortality (OR 0.98, 95% CI 0.89 to 1.08) and is likely to have substantially increased costs.

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

Triple antithrombotic therapy and dual therapy – What is the evidence base?

British Journal of Clinical Pharmacology
Triple antithrombotic therapy refers to concurrent use of oral anticoagulant in combination with dual antiplatelet therapy. Review makes recommendations on duration, noting recommendations in guidelines will remain in flux until there is conclusive evidence about when to step down.

Association between oral anticoagulants and COVID-19 related outcomes: a population-based cohort study

British Journal of General Practice
Among 52,832 current oral anticoagulant (OAC) users and 18,271 non-users with low baseline stroke risk (CHA₂DS₂-VASc score 2), those on OACs had a lower risk of testing positive for SARS-CoV-2 (aHR, 0.77, 95%CI, 0.63–0.95) and severe COVID-19 outcomes than non-users.

Intravenous thrombolytic treatment and endovascular thrombectomy for ischaemic wake‐up stroke

Cochrane Database of Systematic Reviews
Review of 7 trials (n=980) found both IV thrombolysis and endovascular thrombectomy of large vessel occlusion improved functional outcome without increasing risk of death, but, a possible increased risk of symptomatic intracranial haemorrhage with thrombolysis cannot be ruled out.

Treatment Strategies for Proximal Deep Vein Thrombosis: A Network Meta-analysis of Randomised Controlled Trials

European Journal of Vascular and Endovascular Surgery
Review (7 RCTs) found ultrasound assisted catheter directed thrombolysis may improve patency rates vs the other treatment modalities. However, no treatment modality showed superiority in reduction of post-thrombotic syndrome and overall quality of available evidence was poor.

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

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