The Use of Therapeutic-Dose Anticoagulation and Its Effect on Mortality in Patients With COVID-19: A Systematic Review

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.


Major bleeding risk associated with oral anticoagulant in real clinical practice. A multicentre 3‐year period population‐based prospective cohort study

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.



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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 CHMP recommends paediatric license extension and paediatric formulations of dabigatran etexilate (Pradaxa)

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).


COVID-19 rapid guideline: reducing the risk of venous thromboembolism in over 16s with COVID-19 – guidance (NG186)

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:


Antiplatelet and anticoagulant agents for secondary prevention of stroke and other thromboembolic events in people with antiphospholipid syndrome

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.


Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

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%).


Ticagrelor Added to Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack in Prevention of Disabling Stroke: A Randomized Clinical Trial

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

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.


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Value of Coronary Artery Calcium Scanning in Association With the Net Benefit of Aspirin in Primary Prevention of Atherosclerotic Cardiovascular Disease

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

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.


Stroke Prevention in Atrial Fibrillation (AF) Protect and Perfect – Optimising anticoagulation treatment

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.


Prophylaxis of thromboembolism during therapy with asparaginase in adults with acute lymphoblastic leukaemia (ALL)

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.


Evaluation of the incidence of bleeding in patients prescribed rivaroxaban for the treatment and prevention of deep vein thrombosis and pulmonary embolism in UK secondary care: an observational cohort study

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.


Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization: Impact of Concomitant Clopidogrel on Efficacy and Safety

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.


Association of Reperfusion After Thrombolysis With Clinical Outcome Across the 4.5- to 9-Hours and Wake-Up Stroke Time Window: A Meta-Analysis of the EXTEND and EPITHET Randomized Clinical Trials

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).



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Association of Ticagrelor vs Clopidogrel With Net Adverse Clinical Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

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.


Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury: A Randomized Clinical Trial

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

Review outlines the clinical knowledge in this setting, alongside computational modelling frameworks which may provide a mechanistic understanding of the clinical problem of thromboembolisation.


Risk of post-thrombotic syndrome after deep vein thrombosis treated with rivaroxaban versus vitamin-K antagonists: A systematic review and meta-analysis

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

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.


Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): a multicentre, randomised, placebo-controlled, phase 2 trial

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

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.




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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

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.


Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial

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.


Lifelong Aspirin for All in the Secondary Prevention of Chronic Coronary Syndrome: Still Sacrosanct or Is Reappraisal Warranted?

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:

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.


Stroke Thrombolysis With Tenecteplase to Reduce Emergency Department Spread of Coronavirus Disease 2019 and Shortages of Alteplase

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.


Effect of Pre-Hospital Crushed Prasugrel Tablets in Patients with STEMI Planned for Primary Percutaneous Coronary Intervention: The Randomized COMPARE CRUSH Trial

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.


A perfect storm: Root cause analysis of supra-therapeutic anticoagulation with vitamin K antagonists during the COVID-19 pandemic

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.


Investigation into management of venous thromboembolism risk in patients following thrombolysis for an acute stroke

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.



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Multiple versus fewer antiplatelet agents for preventing early recurrence after ischaemic stroke or transient ischaemic attack

Cochrane Database of Systematic Reviews
This review (15 RCTs; n=17,091) concludes multiple antiplatelet drugs reduced risk of stroke recurrence (5.78% v 7.84%, RR 0.73, 95% CI 0.66-0.82; P<0.001) but increased risk of bleeding (e.g. extracranial haemorrhage 6.38% vs 2.81%, RR 2.25, 95% CI 1.88-2.70; P<0.001).


American Society of Hematology publishes draft guidelines on the use of anticoagulation in patients with COVID-19 for review

American Society of Hematology
The DRAFT guidelines, agreed by an international panel, suggest using prophylactic-intensity over intermediate-intensity or therapeutic-intensity anticoagulation in patients with COVID-19 related critical illness or acute illness who do not have suspected or confirmed VTE.


Antiphospholipid Antibodies in Critically Ill Patients With COVID‐19

Arthritis & Rheumatology

Study (n=66) found antiphospholipid antibodies (APSA) were common (47%) in patients in critical condition (CC) but were not present among those not in CC. APSA may be transient & disappear in few weeks, but in genetically predisposed, may trigger condition similar to APS syndrome.

Interventions commonly available during pandemics for heavy menstrual bleeding: an overview of Cochrane Reviews

Cochrane Database of Systematic Reviews
Review (44 RCTs, n=3196) found moderate‐certainty evidence that shows antifibrinolytics & combined hormonal contraceptives reduce heavy menstrual bleeding vs. placebo; and low‐certainty evidence that antifibrinolytics are more effective vs. NSAIDs/short‐cycle progestogens.


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Dabigatran trough concentrations in very elderly patients

European Journal of Hospital Pharmacy
Observational study of 75 patients with atrial fibrillation, found trough concentrations were considerably higher in the highest age category. Dose-normalised medians were 0.66, 0.83 and 1.20 ng/mL/mg in the <75, 75–84 and ≥85 age groups, respectively (p=0.004).


NIHR Alert: Tranexamic acid should not be used for patients with severe gastrointestinal bleeding

National Institute for Health Research
Expert commentary is provided on the HALT-IT (Haemorrhage alleviation with tranexamic acid-Intestinal system) trial of more than 12,000 patients; which showed tranexamic acid does not improve outcomes but increases side effects for this group of patients compared to placebo.


Rivaroxaban and Aspirin in Patients With Symptomatic Lower Extremity Peripheral Artery Disease: A Subanalysis of the COMPASS Randomized Clinical Trial

JAMA Cardiology
Secondary analysis of RCT (n=4129) found risk of major vascular events was greater than 10% over 30 months for high risk patients and treatment with combination of rivaroxaban and aspirin vs aspirin alone resulted in estimated 4.2% absolute risk reduction for major vascular event.



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Evaluating prophylactic heparin in ambulatory patients with solid tumours: a systematic review and individual participant data meta-analysis

The Lancet Haematology
Meta-analysis of individual participant data from 14 of 20 eligible RCTs (n=8278) found LMWH was associated with a lower VTE risk (adjusted RR 0.58; 95% CI 0.47-0.71), but there was no survival benefit. Risk of minor bleeding (1.34; 1.19-1.51), but not major, was increased.


NICE issues draft updated guideline on the management of atrial fibrillation

National Institute for Health and Care Excellence
This DRAFT guideline, which will update CG180 (published June 2014), will cover the diagnosis and management of AF in adults. It aims to ensure people receive the best care to help prevent complications, such as a stroke, and side effects of treatment, such as bleeding.


Low molecular weight heparin for prevention of central venous catheter‐related thrombosis in children

Cochrane Database of Systematic Reviews
Updated review identified 2 studies (n=1135) and noted they did not provide evidence to support this use; and studies did not report on the outcome of catheter occlusion, days of catheter patency, episodes of catheter‐related bloodstream infection and other side effects.


Effect of Clopidogrel and Aspirin vs Aspirin Alone on Migraine Headaches After Transcatheter Atrial Septal Defect Closure: One-Year Results of the CANOA Randomized Clinical Trial

JAMA Cardiology
In prespecified analysis of RCT (n=171), occurrence & severity of migraine attacks (MAs) decreased over time with low percentage of patients with MAs at 6-12-month follow-up; only 1% with new-onset MAs after cessation of clopidogrel at 3 months after atrial septal defect closure.


Vonicog alfa for the treatment and prevention of bleeding in adults with von Willebrand disease

NHS England
NHS England will commission vonicog alfa for the treatment and prevention of bleeding in adults with von Willebrand disease in accordance with the criteria outlined in these documents.



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