Stroke and thromboembolism prevention in atrial fibrillation


Review discusses this association, medical/non-medical therapy for stroke prevention, guideline recommendations for prevention, electrical and pharmacological cardioversion, ablation therapy and antithrombotic medication management, as well as key outstanding research questions.


Personalized Prediction of Cardiovascular Benefits and Bleeding Harms From Aspirin for Primary Prevention: A Benefit–Harm Analysis

Annals of Internal Medicine

This study, based on an analysis of 245,028 persons (43.6% women) aged 30-79yrs without established CVD who had their CVD risk assessed suggests a model that provides a personalised prediction of the benefits and bleeding harms from aspirin when used for primary prevention of CVD.


Head injury: assessment and early management – updated guideline [CG176]

National Institute for Health and Care Excellence

Updates have been made to the recommendations on head CT scans in people on anticoagulant treatment, diagnosis and management of post head injury hypopituitarism, and management of indirect brain injuries.



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Bleeding and New Cancer Diagnosis in Patients with Atherosclerosis


Study (n=27,395) found that in patients with atherosclerosis treated with antithrombotic drugs, any GI bleeding was linked to new GI cancer diagnosis (HR 20.6, 95% CI, 15.2 to 27.8); likewise for genitourinary(GU) bleeding and new GU cancer diagnosis (32.5; 24.7 to 42.9).


Rivaroxaban versus Aspirin in Prevention of Venous Thromboembolism: A Meta-Analysis of 9 Randomized Controlled Trials comprising 7,656 Patients

Thrombosis and Haemostasis

Review of 9 RCTs (n=7,656) found that rivaroxaban reduced VTE vs aspirin (1.3% vs 3.5%, RR 0.36, 95% CI 0.26-0.48), but increased non-major bleeding (11.5% vs 7.5%, 1.28, 1.13-1.44). There was no difference in all-cause mortality and major bleeding.


Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries

Annals of Internal Medicine

Meta-analysis of registry data from 5 countries concludes prevalence of hemophilia is higher than previously estimated: prevalence (per 100,000 males) is 17.1 cases for all severities of haemophilia A, and 3.8 cases for all severities of haemophilia B.



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Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis: A Randomized Clinical Trial

JAMA Neurology

RCT (n=120) found no recurrent VTEs and one major bleeding event with dabigatran and two with warfarin. Authors conclude that both may be effective for recurrent VTE prevention in patients with central venous thrombosis.


Effect of Low-Intensity vs Standard-Intensity Warfarin Prophylaxis on Venous Thromboembolism or Death Among Patients Undergoing Hip or Knee Arthroplasty: A Randomized Clinical Trial

Journal of the American Medical Association

RCT (n=1,650) failed to establish non-inferiority of an INR goal of 1.8 vs 2.5 for VTE prevention post hip or knee arthroplasty (rate of VTE or death was 5.1% for INR target of 1.8 vs 3.8% for INR target 2.5, difference 1.3%, p=0.06 for non-inferiority).


A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI

New England Journal of Medicine

Open label RCT (n=2,488) found a similar efficacy outcome (composite of stent thrombosis, mortality and myocardial infarction) for a CYP2C19 genotype–guided strategy vs standard ticagrelor or prasugrel, but minor bleeding rates were lower (9.8% vs 12.5% p=0.04).


Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial

The Lancet

RCT (n=1,506) found that edoxaban was non-inferior to a vitamin K antagonist (VKA) for bleeding events (annualised rate of 20.7% for edoxaban vs 25.6% for VKAs, HR 0.83, 95% CI 0.65-1.05, non-inferiority margin HR = 1.20, p=0.001 for non-inferiority).


Biosimilars of low molecular weight heparins: Relevant background information for your drug formulary

British Journal of Clinical Pharmacology

This review gives background information on critical factors for the formulary uptake process of LMWHs. It introduces a straightforward instrument to enhance formulary policy making in a transparent, rational way (the System of Objectified Judgment Analysis/Infomatrix model).


2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer

The Lancet Oncology

This guidance is based on a systematic review of the literature. Results from head to head trials comparing DOACs with LMWHs are included for information in the guidance along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.


Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease

New England Journal of Medicine

Study of 2236 AF patients reports rivaroxaban monotherapy is non-inferior to combination therapy with antiplatelet+rivaroxaban for the primary efficacy end point (composite of stroke, systemic embolism, MI, unstable angina requiring revascularization, or death from any cause).


Estimating individual lifetime benefit and bleeding risk of adding rivaroxaban to aspirin for patients with stable cardiovascular disease: results from the COMPASS trial

European Heart Journal

Predicted individual gain in life expectancy free of stroke or MI from added low-dose rivaroxaban had a median of 16 months (range 1–48 months), while predicted individualized lifetime lost in terms of major bleeding had a median of 2 months (range 0–20 months).


Ticagrelor in Patients with Stable Coronary Disease and Diabetes

New England Journal of Medicine

RCT (n=19,220; median follow-up 39.9 months) reported lower incidence of ischaemic cardiovascular events with ticagrelor + aspirin vs aspirin (7.7 vs. 8.5%; HR, 0.90; 95% CI, 0.81 to 0.99; P=0.04) but higher incidence of major bleeding (2.2 vs. 1.0%; 2.32; 1.82 to 2.94; P<0.001).


Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes

New England Journal of Medicine

Open-label RCT (n=4018) reported incidence of death, MI, or stroke was significantly lower in the prasugrel group vs ticagrelor group (6.9% vs 9.3%; HR, 1.36; 95% CI, 1.09 to 1.70; P=0.006) with no difference in major bleeding (4.8% vs 5.4%; 1.12; 0.83 to 1.51; P=0.46).


Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

The Lancet

Sub-group analysis (n=11,154) reported that addition of ticagrelor to aspirin reduced cardiovascular death, MI, and stroke vs placebo for a median of 3.3 years (7.3 vs 8.6% in the PCI group; HR 0.85; 95% CI 0.74–0.97; p=0.013), although with increased risk of major bleeding.


2019 European Society of Cardiology Guidelines for the diagnosis and management of acute pulmonary embolism

European Heart Journal

These guidelines, an update of the 2014 guidelines, outline the optimal diagnosis, assessment, and treatment of patients with pulmonary embolism.



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Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin


RCT (n=17,598 followed up for median 3.01 years, with 53,152 patient-years of follow-up) found no statistically significant difference between pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% placebo group; OR 1.33; 95% CI, 1.01–1.75).


Increasing number of patients prescribed risky anticoagulant drug combinations

Pharmaceutical Journal

Statistics from the Medication Safety Dashboard show that between Sept 18 and Nov 18, there were more than 14,000 patients in England prescribed an NSAID with an anticoagulant and more than 30,000 patients prescribed an antiplatelet and anticoagulant without gastro-protection.



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Venous thromboembolism prophylaxis strategies for people undergoing elective total knee replacement: a systematic review and network meta-analysis

The Lancet Haematology

Review (25 RCTs) found that vs no prophylaxis, rivaroxaban was most effective for prevention of DVT (RR 0.12; 95% CI 0.06–0.22). LMWH, vs no prophylaxis was found to be more effective for pulmonary embolism and best for major bleeding but these findings are highly uncertain.


Emicizumab as prophylaxis in people with severe congenital haemophilia A without factor VIII inhibitors (all ages)

NHS England

NHS England will commission emicizumab as prophylaxis in adults and children with severe congenital haemophilia A (defined as factor VIII level <1 IU/dL, or <1% of normal) without current inhibitors to prevent bleeding episodes.


Catheter Ablation for Atrial Fibrillation in 2019

Journal of the American Medical Association

This article reviews management approaches to atrial fibrillation (AF), including assessment of the need for anticoagulation, and controversies over the need for rhythm control and the role of catheter ablation for maintaining sinus rhythm and reducing AF-associated symptoms.


Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps: A Randomized Controlled Trial

Annals of Internal Medicine

RCT (n=184) found patients on continuous anticoagulants +cold snare polypectomy (CSP;without electrocautery) did not have increased incidence of polypectomy-related major bleeding, and procedure time and hospitalisation were shorter vs. periprocedural heparin bridging plus hot SP.


Effect of Recombinant Activated Coagulation Factor VII on Hemorrhage Expansion Among Patients With Spot Sign–Positive Acute Intracerebral Hemorrhage: The SPOTLIGHT and STOP-IT Randomized Clinical Trials

JAMA Neurology

RCTs included 69 patients and found that recombinant activated coagulation factor VII did not significantly improve radiographic or clinical outcomes vs. placebo among patients with spot sign–positive intracerebral haemorrhage treated a median of ~3 hours from stroke onset.


Outcomes Associated With Clopidogrel-Aspirin Use in Minor Stroke or Transient Ischemic Attack: A Pooled Analysis of Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and

JAMA Neurology

Analysis of POINT and CHANCE trials (n=10,051) found clopidogrel-aspirin treatment reduced risk of major ischaemic events at 90 days vs. aspirin, that appeared to be confined to the first 21 days (5.2% vs 7.8%; HR 0.66; 95% CI, 0.56-0.77; p <0 .001), but not from day 22 to day 90.


Prevention of Stroke in Atrial Fibrillation After Coronary Stenting: Systematic Review and Network Meta-Analysis


Review of 3 RCTs and 15 observational studies (total n=23,478) found that DOACs were associated with less major bleeding and major cardiovascular adverse effects, but vitamin K antagonists were associated with decreased mortality and stroke.



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Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies

The Lancet Haematology

Study (93 children) found that bodyweight adjusted rivaroxaban appears to be safe in children (no major bleeds, 4% rate of non-major bleed and no recurrent VTEs). Doses for <20kg showed low exposure, so the dosages for this group will be adjusted for the phase 3 study.


A Meta-Analysis of Aspirin for the Primary Prevention of Cardiovascular Diseases in the Context of Contemporary Preventive Strategies

American Journal of Medicine

Analysis of 14 RCTs(n=164,751) found aspirin decreases MI risk at expense of increased risks for major bleeding (BD) and haemorrhagic stroke. With contemporary aggressive preventive strategies, effect on MI risk seems to be much attenuated whereas its harmful effects on BD remain.


NIHR Signal: On balance, antiplatelet drugs may be restarted for stroke survivors who have bled into the brain

National Institute for Health Research

Expert commentary is provided of UK trial of 537 adults (RESTART) on antiplatelets before intracerebral haemorrhage, which found no material difference in risk of further bleeding or occlusive vascular event if they restarted on the drugs when feasible.


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NIHR Signal: Reminders to assess clotting risk increase the use of preventive measures

National Institute for Health Research

Expert commentary is provided for a review of 13 RCTs (n=35,997) which found that alert based interventions increased the proportion of patients who received mechanical or drug prophylaxis vs standard care. Unfortunately, trial data are lacking on multifaceted interventions.


Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis

The Lancet Neurology

Scottish cohort study (n=300) found antithrombotic therapy linked to lower risk of subsequent intracranial haemorrhage (ICH) or focal neurological deficit. Meta-analysis of 6 cohort studies (n=1342) also noted lower ICH risk (3 vs. 14%; IRR 0.25; 95% CI,0.13–0.51;p<0.0001).


Meta-Analysis of Oral Anticoagulant Monotherapy as an Antithrombotic Strategy in Patients With Stable Coronary Artery Disease and Nonvalvular Atrial Fibrillation

American Journal of Cardiology

Analysis of 6 trials (n=8855) found no significant difference in major adverse CV event in patients on oral anticoagulant (OAC) plus single antiplatelet therapy (SAPT) vs. OAC monotherapy. OAC plus SAPT was linked to higher risk of major bleeding (HR 1.61; 95% CI 1.38-1.87).


Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant

JAMA Internal Medicine

Cohort study (n=3007) followed up post-operatively for 30 days suggests DOAC therapy interruption without heparin bridging or coagulation function testing before elective surgery were associated with low rates of major bleeding (<2%) and arterial thromboembolism.


Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update

Journal of Clinical Oncology

This updated guideline now recommends thromboprophylaxis with apixaban, rivaroxaban, or low molecular weight heparin to selected high-risk outpatients with cancer, whilst rivaroxaban and edoxaban have been added as options for VTE treatment.


Thromboembolic events around the time of cardioversion for atrial fibrillation in patients receiving antiplatelet treatment in the ACTIVE trials

European Heart Journal

Study (n=962) found that thromboembolic risk increased in 30 days before cardioversion and persisted until 30 days post-cardioversion (0.47% and 0.96%, respectively; HR 2.2, 95% CI 0.7–7.1). Authors suggest that this increased risk may not be entirely causal.



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Revised SPC: Xarelto (rivaroxaban) tablets

electronic Medicines compendium

SPC now advises that rivaroxaban should not be used for thromboprophylaxis in patients having recently undergone transcatheter aortic valve replacement as the safety and efficacy have not been studied in this population.


Educational Risk Minimisation Materials to help reduce the risk associated with the use of combined hormonal contraceptives (CHCs)


Bayer has published a checklist for prescribers, a Q&A on important information for women and a summary of important information about risk of blood clots with combined hormonal contraceptives, for all Bayer CHC products.



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Clinical Effectiveness of Direct Oral Anticoagulants vs Warfarin in Older Patients With Atrial Fibrillation and Ischemic Stroke: Findings From the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study

JAMA Neurology

Data from 11,662 patients discharged after stroke shows those on DOACs (v warfarin) had fewer deaths (HR 0.88, P<0.001), all-cause readmissions (0.93; P=0.003), CV readmissions (0.92, P=0.02), haemorrhagic strokes (0.69, P=0.02), and hospitalisation with bleeding (0.89, P=0.009).


Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis

British Medical Journal

Review (18 studies;n=7515) found in patients with 1st episode unprovoked VTE who completed ≥3 months anticoagulation, risk of recurrent VTE was 10% in 1st year after treatment, 16% at 2 years, 25% at 5 years, and 36% at 10 years, with 4% of recurrent VTE events resulting in death.



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Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps: A Randomized Controlled Trial

Annals of Internal Medicine

This RCT (n=184) suggests small colorectal polyps may be resected safely with cold-snare polypectomy while oral anticoagulation continues, compared to heparin bridging with hot-snare polypectomy, and was associated with a lower incidence of major bleeding.


Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis

Annals of Internal Medicine

Review of 45 RCTs (n=34,082) concludes in early-stage CKD, non–vitamin K oral anticoagulants (NOACs) had benefit–risk profile superior to that of vitamin K antagonists (VKAs). For advanced CKD or ESKD, there was insufficient evidence to establish benefits or harms of VKAs v NOACs.


Rivaroxaban (Xarelto▼): reminder that 15 mg and 20 mg tablets should be taken with food

Medicines and Healthcare products Regulatory Agency

MHRA has received a small number of reports suggesting lack of efficacy (thromboembolic events) in patients taking 15 mg or 20 mg rivaroxaban on an empty stomach. Healthcare professional are advised to remind patients to take 15 mg or 20 mg rivaroxaban tablets with food.


Direct Acting Oral Anticoagulants (DOACs) in Renal Impairment: Practice Guide to Dosing Issues

Specialist Pharmacy Service

This paper explains the background to dosing decisions for DOACs in patients with impaired renal function and focusses on the use of DOACs in patients with AF. It provides case study examples from current clinical practice and is intended as a practice aid.



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