Anticoagulation news items. Week commencing 14th December 2020
Discontinuation of oral anticoagulation in atrial fibrillation and risk of ischaemic stroke
Heart
Population-based cohort study with nested case–control analysis (76 882 UK;41526 Denmark) found pts who discontinued oral anticoagulation therapy had a two to threefold higher risk of ischaemic stroke vs current users (UK OR 2.99; 95% CI 2.31 to 3.86: Denmark 2.30; 1.79 to 2.95).
Thrombosis and Haemostasis
Study reports no excess in GI bleeding in patients who received apixaban, including those with GI cancer; major bleeding occurred in 22 of 576 on apixaban (3.8%) and in 23 of 579 patients on dalteparin (4.0%). The sites of major bleeding were similar between the two groups.
Stroke Prevention in Atrial Fibrillation: Looking Forward
Circulation
Review summarises the major advances in stroke prevention for patients with atrial fibrillation during the past 30 years and focuses on novel diagnostic and treatment approaches currently under investigation in ongoing clinical trials.
Medicines and Healthcare products Regulatory Agency
Erythromycin should not be given to patients with a history of QT interval prolongation or ventricular cardiac arrhythmia. A potential drug interaction between rivaroxaban and erythromycin resulting in increased risk of bleeding has also been identified.
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 7th December 2020
The Lancet Haematology
RCT (n=328) found age/weight adjusted dabigatran non-inferior to standard of care (LMWH/unfractionated heparin/vit K antagonists/fondaparinux) for the composite efficacy endpoint of thrombus resolution, & no recurrent VTE or VTE-death: 42%vs 46%; p<0.0001).
European Heart Journal
Review (5 RCTs, n=32,145) reports 1–3 months of dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor single antiplatelet therapy is associated with lower major bleeding and similar stent thrombosis, all-cause death, myocardial infarction & stroke vs. prolonged DAPT.
JAMA Neurology
Prospective study (n=1,827) found prehospital tranexamic acid increased mortality in patients with isolated severe traumatic brain injury (OR 4.49; 95% CI, 1.57-12.87; p=0.005), highlighting need for judicious use of the drug when there is no evidence for extracranial haemorrhage.
American Journal of Cardiology
Review of RCTs investigating time in therapeutic range (TTR) found, across all TTR levels, DOACs had lower risk of stroke or systemic embolism vs warfarin (HR 0.73, 95%CI 0.61-0.88). There was a lower risk of major bleeding for DOACs vs warfarin in medium or low TTR only.
European Journal of Hospital Pharmacy
Study in 80 patients on oral anticoagulants who visited the emergency department (ED) for gastrointestinal bleeding found 13.7% revisited the ED for bleeding episodes 30 days after hospital discharge, with no particular differences between the types of anticoagulant prescribed.
The Lancet
This review article looks at management of retinal vascular occlusions, which are common causes of visual impairment. Acute management of retinal artery occlusions involves a multidisciplinary approach, whereas treatment of retinal vein occlusions is provided by ophthalmologists.
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 30th November 2020
Implementing point-of-care D-dimer tests for deep vein thrombosis (DVT)
City Health Care Partnership CIC
NG158 recommends considering the use of POC D-dimer tests as an alternative to laboratory D-dimer tests. Since implementing the tests, the main advantage has been the reduction in time from the person presenting, to diagnosis and receiving treatment.
Heart
Prospective cohort study (n=1,903) found major bleeding was significantly lower with rivaroxaban as compared to use of vitamin K antagonists (7.4 vs 14.6 per 100 patient years, HR 0.66, 95% CI 0.43-0.99). This was largely driven by lower risk of intracerebral bleeding.
British Journal of General Practice
In this analysis (n=438), 39.4% received at least one inappropriate DOAC prescription – mainly under-dosing (31.3%). Factors independently associated with under-dosing were older age, those with kidney failure, a higher risk for ischemic stroke and/or a higher risk for bleeding.
British Journal of Clinical Pharmacology
This short report describes research suggesting the risk factors for kidney injury in people using warfarin (male sex and age ≥80 years) were different to those in people using DOACs (weight ≥80 kg and use of dabigatran); these factors may be associated with 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. Week commencing 23rd November 2020
Clinical and Applied Thrombosis/Hemostasis
Of 8 studies in review, 3 retrospective cohort studies reported reduction in mortality rate, while 5 other studies showed no mortality benefits in this population. There was slight tendency toward reduction in mortality rate among mechanically-ventilated patients with COVID-19.
Safety of direct oral anticoagulant exposure during pregnancy: a retrospective cohort study
The Lancet Haematology
Study (n=1,193 reports of exposure, mean duration 5.3 weeks) finds that although reports are missing important details & predominantly describe rivaroxaban exposures, available data do not suggest direct oral anticoagulant exposure in pregnancy carries a high risk of embryopathy.
Diagnosis, Management, and Pathophysiology of Arterial and Venous Thrombosis in COVID-19
Journal of the American Medical Association
Review summarises pathophysiology underlying thrombotic diathesis characteristic of acute covid-19 infection and recommendations for prevention, diagnosis & management of complications e.g. acute myocardial infarction, ischaemic stroke, and venous thromboembolism.
Pharmacist-led atrial fibrillation case finding programme prevents an estimated 90 strokes
Pharmaceutical Journal
Following the pharmacist-led programme, Quality Outcomes Framework results for 2019–2020 across 23 CCGs showed an encouraging increase in the rate of anticoagulation of 3.45% in those with a record of a CHA2DS2-VASc score of ≥ 2 vs. 1.38% for all other CCGs across England.
British Journal of Clinical Pharmacology
Study (n=47,469) found high and low‐dose DOACs linked to reduced risk of intracranial haemorrhage (aHR 0.55, 95% CI 0.37–0.82 & 0.54, 0.26–1.12 respectively), and reduced risk of other major bleeding events, irrespective of duration and indication, vs. vitamin K antagonists.
Direct oral anticoagulants: evidence and unresolved issues
The Lancet
In this Therapeutics paper, the authors review pharmacology, the evidence that led to approval and incorporation into treatment guidelines, key unresolved issues, and future perspectives for the development of oral anticoagulants.
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 16th November 2020
European CHMP recommends paediatric license extension and new strength of rivaroxaban (Xarelto)
European Medicines Agency
The license extension, treatment of VTE and prevention of VTE recurrence in term neonates, infants and toddlers, children, and adolescents aged < 18 years after at least 5 days of initial parenteral anticoagulation treatment, is supported by a new 1 mg/ml oral suspension.
European Medicines Agency
Paediatric license extension, treatment of VTE and prevention of recurrent VTE from birth to <18 years of age, is supported by a new pharmaceutical form and strength – coated granules (20 mg, 30 mg, 40 mg, 50 mg, 110 mg, 150 mg) and oral solution (6.25 mg/ml).
Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19
The Lancet Respiratory Medicine
In this Personal View, a proactive follow-up strategy to evaluate residual clot burden, small vessel injury, and potential haemodynamic sequelae is proposed, as well as a nuanced approach looking beyond the clot, and at the state of perfusion of lung tissue.
Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve
New England Journal of Medicine
RCT (n=1,005) reports rivaroxaban was non-inferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months; 347.5 vs 340.1 days, respectively (difference 7.4 days; 95% CI −1.4 to 16.3; P<0.001).
National Institute for Health and Care Excellence
This guideline covers pharmacological VTE prophylaxis for patients being treated for COVID-19 pneumonia. It includes patients receiving treatment in hospital or in a community setting such as a 'hospital at home' service or COVID-19 'virtual ward'.
Draft updated venous thromboembolic diseases quality standard out for consultation
National Institute for Health and Care Excellence
This DRAFT quality standard update covers reducing the risk of VTE in people aged ≥16 who are in hospital, and diagnosing and treating VTE in all people aged ≥18. It describes high-quality care in priority areas for improvement.
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 9th November 2020
Cochrane Database of Systematic Reviews
Review (8 RCTs; n=811; moderate‐certainty evidence) concludes that DOACs probably increase risk of stroke but may not alter risk of any thromboembolic events, major bleeding, mortality or clinically‐relevant non‐major bleeding vs standard‐dose warfarin.
The Lancet
Review (4 RCTs; n=843) found intravenous alteplase resulted in better functional outcome (score of 0–1 on modified Rankin Scale) at 90 days vs placebo/standard care (47% vs 39%; adjusted OR 1.49; 95% CI 1.10–2.03) but with higher risk of intracranial haemorrhage (11% vs <2%).
JAMA Neurology
In THALES RCT (n=11 016 with non-cardioembolic, non-severe ischaemic stroke or high-risk TIA), ticagrelor + aspirin significantly reduced 30-day risk of disabling stroke or death vs aspirin alone (4.0% vs 4.7%; P = 0.04) and showed 23% reduction of total disability burden.
The assessment of venous thromboembolism risks associated with pregnancy
Healthcare Safety Investigation Branch
Following an investigation into the death of a mother who suffered a pulmonary embolism 5 weeks after the birth of her third child, this investigation will look at the assessment and communication of the risk of venous thromboembolism in pregnant and postnatal women.
Heparin-Induced Thrombocytopenia in Severe COVID-19
Circulation
Case study (n=7, France) reports critical COVID-19 patients develop life-threatening coagulopathy & complications that justify aggressive anticoagulation; but warn occurrence of Heparin-Induced Thrombocytopenia increases and may alter risk–benefit balance of anticoagulation.
Venous thromboembolism risk with JAK inhibitors: A Meta‐analysis
Arthritis and Musculoskeletal Alliance
Review of 42 studies found no increased risk, with incidence rates for VTE, PE & DVT with JAK inhibitor use of 0.68 (95%CI 0.36-1.29), 0.44 (0.28-0.70) and 0.59 (0.31-1.15) respectively. Authors state data do not support current warnings around VTE risk for JAK inhibitors.
Sanofi Genzyme pauses haemophilia clinical development program for fitusiran
Biospace Inc.
Program for this once-once monthly, subcutaneously dosed non-factor-replacement therapy that leverages small interfering RNA to target and decrease antithrombin has been paused to allow investigation of reports of non-fatal thrombotic events in patients in the trials.
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 2nd November 2020
JAMA Cardiology
Study (n=2191) found higher coronary artery calcium (CAC) is associated with atherosclerotic cardiovascular disease (CVD) & bleeding events. High CAC score denotes net benefit from aspirin for primary prevention, but only in setting of lower bleeding, and intermediate CVD risk.
Antithrombotic therapy for patients with chronic coronary syndromes
Heart
Review evaluates the pathophysiology and pharmacology of atherothrombosis, highlights current RCT evidence and discusses the content and application of the European Society of Cardiology 2019 chronic coronary syndromes guidelines.
Kent Surrey Sussex Academic Health Science Network (KSS AHSN)
The tool used in this project, assisted GP practices with complete management of patients with AF; generating lists of diagnosed AF patients where clinical intervention is missing along with opportunistic prompts (aligned to AF NICE CG180 guidelines).
Diagnosis and Treatment of Lower Extremity Venous Thromboembolism
Journal of the American Medical Association
This review summarises recent developments in the diagnosis and management of lower extremity deep vein thrombosis, including discussion of risk factors, clinical presentation, and risks for pulmonary embolism and other complications.
Prophylactic anticoagulants for people hospitalised with COVID‐19
Cochrane Database of Systematic Reviews
Review of 7 studies (n=5929) concludes there is insufficient evidence to determine risks and benefits of prophylactic anticoagulants for people hospitalised with COVID‐19. There are 22 studies in >15,000 participants underway however, which will provide more robust evidence.
Cochrane Database of Systematic Reviews
Review of 23 non-randomised studies (no RCTs were appropriate for inclusion) concludes it is unclear from the available evidence if thromboprophylaxis used for adults with ALL treated with asparaginase is associated with any appreciable benefits or harms.
BMJ Open
Study (n=4,846) found a low rate of major bleeding in gastrointestinal, intracranial and urogenital sites when using rivaroxaban for treatment of deep vein thrombosis/pulmonary embolism (<1% for all). Authors report this magnitude of risk is consistent with trial data.
Circulation
Review of the VOYAGER PAD trial found rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events irrespective of clopidogrel use. Safety was also consistent regardless of clopidogrel, but with a trend for more major bleeding with clopidogrel use >30 days.
JAMA Neurology
Meta-analysis (n=270) found that reperfusion was associated with significantly improved functional outcome without increased risk of symptomatic haemorrhage support when used between 4.5 to 9-hours post stroke (SPC recommends treatment within 4.5 hours of stroke).
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 26th October 2020
Journal of the American Medical Association
Study (n=31,290 propensity matched pairs) reports the 1-yr risk of net adverse clinical events was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; hazard ratio, 1.05 [95% CI, 1.00-1.10]; p=.06).
Revised SPC: Alprolix (eftrenonacog alfa) powder and solvent for solution for injection
electronic Medicines compendium
Factor IX inhibition, hypersensitivity and Injection site erythema have been added as common adverse events.
Journal of the American Medical Association
In 596 critically ill patients, anticoagulation with regional citrate, increased filter life span vs systemic heparin anticoagulation (47 vs 27 hours) but the trial was underpowered to reach conclusions regarding mortality (90-day mortality 51.2% vs 53.6%).
Fibrosis, atrial fibrillation and stroke: clinical updates and emerging mechanistic models
Heart
Review outlines the clinical knowledge in this setting, alongside computational modelling frameworks which may provide a mechanistic understanding of the clinical problem of thromboembolisation.
Thrombosis Research
Review (7 studies; n=2364) found that in comparison to vitamin-K antagonists, rivaroxaban has potential to reduce post-thrombotic syndrome events [OR 0.53, 95% CI: 0.43–0.65, p<0.00001], but well-designed studies with larger sample sizes are needed to corroborate these findings.
Clinical and budget impacts of changes in oral anticoagulation prescribing for atrial fibrillation
Heart
English study found that despite nearly one million additional DOAC prescriptions and substantial associated spending in the latter part of this study, the decline in AF-related stroke (fell by 11.3%) led to incremental savings (£289 per-patient) at the national level.
The Lancet Neurology
Study (n=100) does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth (occurred in 26 [52%] placebo vs. 22 [44%] tranexamic acid group; OR 0·72;95% CI 0·32–1·59, p=0.41), although treatment was safe with no increase in thromboembolic complications.
Anticoagulation in atrial fibrillation
Heart
Review notes 1 in 3 people will be diagnosed with AF at some point in their lives; over 1.2m individuals in UK have been diagnosed with AF; thousands still remain undiagnosed, and risk of AF-related stroke can be mitigated through anticoagulation, with a 66% risk reduction.
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 19th October 2020
Rituximab for treating inhibitors in people with inherited severe haemophilia
Cochrane Database of Systematic Reviews
This review did not identify any relevant randomised controlled trials. The research evidence available was limited to case reports and case series therefore no conclusions could be drawn on the efficacy and safety of rituximab for treating inhibitors in people with haemophilia.
Topline Phase III data of avatrombopag for treatment of chemotherapy-induced thrombocytopenia
Biospace Inc.
Though avatrombopag increased platelet counts relative to placebo, the study did not meet the composite primary endpoint of avoiding platelet transfusions, chemotherapy dose reductions by 15% or greater, and chemotherapy dose delays by four days or more.
Cessation of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation
Heart
In 'real world' cohort (n=1415), persistence of DOAC use was found to be high with only 8.8 cessations/100 patient-years follow-up and rate of serious adverse events rate was low at 1.6/100 patient-years; most common cause of cessation of index DOAC (53.1%) was patient choice.
JAMA Neurology
Analysis (n=3699) found those with cerebral microbleeds had higher rates of recurrent stroke, ischaemic stroke, intracerebral haemorrhage, and mortality during 11 months of follow-up, but this did not appear to influence the effects of rivaroxaban (15mg) on clinical outcomes.
Circulation
This narrative review discusses recent trials that inform the current use of aspirin in the secondary prevention of chronic coronary syndrome (CCS), a new term for stable coronary artery disease defined in the 2019 European Society of Cardiology guidelines.
Revised SPC: Praxbind (idarucizumab) 2.5 g/50 mL solution for injection/infusion
electronic Medicines compendium
Section 5.1 has been updated with information on a paediatric patient (between 16-<18 years old) treated with idarucizumab during an open-label safety trial.
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 12th October 2020
Warfarin and other anticoagulants – monitoring of patients during the COVID-19 pandemic
Medicines and Healthcare products Regulatory Agency
MHRA has published guidance following concerns over an apparent increase in the number of patients taking warfarin found to have elevated INR values during the pandemic; and reminds healthcare professionals and patients that continued close INR monitoring is crucial.
JAMA Neurology
Viewpoint from US perspective notes the situation of an acute stroke emergency is a particularly vulnerable situation for exposure and transmission of COVID-19; it advocates for expanded usage of tenecteplase as means of avoiding spread and easing potential shortages of alteplase.
Circulation
RCT (n=727) found pre-hospital administration of loading dose of crushed prasugrel tablets does not improve TIMI 3 flow in infarct-related artery pre-PCI or complete ST-segment resolution 1h post-PCI vs. intact tablets, and there were no differences in ischaemic events at 30 days.
Thrombosis Research
Study of INR results show significant increase in high INRs during COVID-19 pandemic, with majority occurring after introduction of lockdown, with 30/3214 (0.9%) INR samples >8.0 (n=30) vs. 6/4079 (0.1%; n=6) during same period in previous year (OR 6.3, 95% CI, 2.6–15.2; p<0.001).
Warfarin in patients with mechanical heart valves
British Medical Journal
Practice article highlights these patients require lifelong anticoagulation with warfarin to prevent thromboembolism, low dose aspirin can be added in patients with higher risk of thromboembolic events, and DOACs are not currently recommended as safety has not been established.
Healthcare Safety Investigation Branch
Follow review of a case of a 78-year old woman who suffered a pulmonary embolism whilst recovering from a stroke in hospital, this report makes a safety recommendation for a stroke specific venous thromboembolism assessment tool.
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
