Anticoagulation news items. Weeks commencing 31st January 2022
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:
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Anticoagulation news items. Weeks commencing 17th and 24th January 2022
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.
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.
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:
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Anticoagulation news items. Weeks commencing 3rd and 10th January 2022
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.
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.
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:
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Anticoagulation news items. Weeks commencing 6th, 13th and 20th December 2021
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.
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.
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.
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.
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).
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.
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.
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.
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.
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
Anticoagulation news items. Weeks commencing 22nd and 29th November 2021
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:
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Anticoagulation news items. Week commencing 15th November 2021
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.
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:
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Anticoagulation news items. Week commencing 8th November 2021
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.
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:
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Anticoagulation news items. Week commencing 1st November 2021
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:
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Anticoagulation news items. Week commencing 25th October 2021
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
Anticoagulation news items. Week commencing 18th October 2021
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%).
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.
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.
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:
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