Stroke and death in elderly patients with atrial fibrillation in Japan compared with the United Kingdom


Study (n=3129) found elderly (age ≥75 years) patients with atrial fibrillation in both Japan and the UK are at similarly high risk of stroke and death. Appropriate oral anticoagulation was still underused (<60%) in both populations.


Eyes on Evidence: Perioperative anticoagulation for people with atrial fibrillation

National Institute for Health and Care Excellence

A commentary is provided on RCT in people with AF who stopped taking warfarin before elective surgery/invasive procedure, which found people who did not receive 'bridging' heparin had a lower risk of bleeding and no higher risk of thromboembolism than those who received it.


Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study

British Medical Journal

Danish cohort study (n=61,678) found all NOACs seem to be safe and effective alternatives to warfarin (WF) in a routine care setting. No significant difference was found for ischaemic stroke. Risks of death, any or major bleeding were lower for apixaban and dabigatran vs. WF.


Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial

British Medical Journal

In trial (n=18,201),~75% patients had polypharmacy; this subgroup had increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic/bleeding complications. Apixaban was more effective than warfarin regardless of number of concomitant drugs.


Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

The Lancet Neurology

Over 90% stroke burden (SB) is attributable to modifiable risk factors, and achieving control of behavioural/metabolic risk factors could avert over three-quarters of global SB. Air pollution has emerged as a significant contributor to SB especially in low/middle-income countries.


NIHR Signal: An anticoagulant, bivalirudin, may not be safer than the alternative, heparin, when unblocking arteries in the heart

National Institute for Health Research Signal

This is an expert commentary of a meta-analysis which found that bivalirudin as an alternative to heparin to prevent clotting during percutaneous coronary intervention may be ineffective in preventing recurrence of blockage or further heart attacks.


Prolonged dual antiplatelet therapy in stable coronary disease: comparative observational study of benefits and harms in unselected versus trial populations

British Medical Journal

The PEGASUS-TIMI-54 trial was one of first to inform management of high risk patients, but this analysis has shown that real world patients who survive ≥1 year after acute MI are at yet greater risk, amplifying potential of dual antiplatelet therapy to improve prognosis.


Risk of venous thromboembolism in cancer patients treated with epoetins or blood transfusions

British Journal of Clinical Pharmacology

Study of 69,888 patients identified 3316 cases of venous thromboembolism (VTE). There was a higher risk of VTE with epoetins (OR 1.31 (95% CI 1.03-1.65)), transfusions (2.33 (2.03-2.66)), and epoetins and transfusions (2.24 (1.34-3.77)).


Direct oral anticoagulants for stroke prevention in patients with atrial fibrillation: meta-analysis by geographic region with a focus on European patients

British Journal of Clinical Pharmacology

This review of 5 trials (n=72,673) found that direct oral anticoagulants were not superior to warfarin for prevention of stroke and systemic embolic events (RR=0.97 95% CI=0.85-1.11) in European patients (n=32,089), but were with patients from other regions (0.72, 0.63-0.83).



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Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines


These guidelines refer to patients undergoing elective endoscopic gastrointestinal procedures, and make recommendations on the management antiplatelet/anticoagulant therapy based on the risk of procedural haemorrhage vs. thrombosis if therapy is discontinued.


Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: Executive summary—Revision 1

European Heart Journal

This guide has been updated including new information with a balanced guide in the areas where prospective data are still lacking. Changes include a discussion on the definition of 'non-valvular AF' and eligibility for DOAC therapy and finalised information on edoxaban.


Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis

The Lancet Neurology

Analysis (n= 6756 in 9 trials of alteplase vs. control) found that in alteplase group, net outcome is predicted both by time to treatment (faster time increasing % achieving excellent outcome) and stroke severity (more severe increasing absolute risk of intracerebral bleed).


One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial

British Medical Journal

Non-inferiority trial (n=518) found that stopping elastic compression stockings (ECS) after one year in compliant patients with proximal deep venous thrombosis (DVT) seemed not to be non-inferior to continuing ECS therapy for 2 years, with an NNT of 14.


Antithrombotic therapy in heart failure (HF) patients with and without atrial fibrillation (AF): update and future challenges

European Heart Journal

This review provides a perspective on the use of antithrombotic treatments in patients with both AF and HF, and in patients with HF and sinus rhythm, with particular attention to the NOACs, and provides background for therapeutic, outcome and trial improvement.


Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

New England Journal of Medicine

In this RCT (n=7513), the primary efficacy outcome of composite asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism was not statistically significant (6.9% for betrixaban v 8.5% for enoxaparin in the group with raised d-dimer levels.



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FDA approves Afstyla for patients with haemophilia A


Afstyla, a novel recombinant factor VIII single-chain therapy, designed for long-lasting protection from bleeds with 2-3 x weekly dosing. It can also be used as on-demand treatment to control bleeds, and in perioperative management of bleeding.


Cryptogenic Stroke

New England Journal of Medicine

This feature article begins with a case highlighting a common clinical problem, cryptogenic stroke. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.


Prediction of rates of thromboembolic and major bleeding outcomes with dabigatran or warfarin among patients with atrial fibrillation: new initiator cohort study

British Medical Journal

A comparison of bleeding rates seen in a cohort (n=21934) of patients with AF treated with warfarin v dabigatran with what was predicted using risk assessment models & data from RCTs showed good correlation between models & real-life but RCTs underestimate risk of major bleeding.


Reversal of the anticoagulant effect of dabigatran: idarucizumab (ESNM73)

National Institute for Health and Care Excellence

This review looks at the evidence for the efficacy/safety of idarucizumab for reversing the anticoagulant effect of dabigatran etexilate. There are
currently no other licensed agents to reverse the anticoagulant effect of dabigatran etexilate (or any other NOAC).


Individualising Duration of Dual Antiplatelet Therapy After Acute Coronary Syndrome or Percutaneous Coronary Intervention


This review, based on 2 case vignettes, discusses dual antiplatelet therapy in the management of patients with acute coronary syndromes and those undergoing percutaneous coronary intervention, in the context of balancing optimal duration with the risk of adverse bleeding effects.


Use of antipsychotics and risk of myocardial infarction: a systematic review and meta-analysis

British Journal of Clinical Pharmacology

This review of 9 observational studies found that the odds for developing an MI were higher with antipsychotic users vs never users (OR=1.88, 95%CI=1.39-2.54). Short term users (<30 days) and those with schizophrenia had a more pronounced risk.


The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis

European Heart Journal

This review of 12 studies (n=99,996) found that non-paroxysmal AF was associated with higher rates of thromboembolism than parosxysmal AF (unadjusted RR=1.355, 95%CI= 1.169-1.571).



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Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials

The Lancet

Data from 12 trials (n=15,778) found aspirin reduced 6 week risk of recurrent ischaemic stroke (IS) vs. placebo by ~ 60% (HR 0.42, 95% CI, 0.32–0.55, p<0.0001) and disabling or fatal IS by ~70% (0.29, 0.20–0.42, p<0.0001), with greatest benefit in patients with TIA/minor stroke.


Coronary-Artery Bypass Grafting

New England Journal of Medicine

This review covers evidence from trials of CABG vs. medical therapy or vs. percutaneous coronary intervention, as well as complicating factors, indications and evaluation for CABG, morbidity and mortality, and secondary prevention.


Which Oral Anticoagulant for Atrial Fibrillation?

Journal of the American Medical Association

This Medical Letter review summarises the newly available oral anticoagulants and compares them with commonly prescribed warfarin.


Should prophylactic doses of low molecular weight heparins be used in patients with renal impairment?

South West Medicines Information & Training

This updated Medicines Q&A reviews the current literature regarding the use of prophylactic doses of low molecular weight heparins in patients with renal impairment.



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Clinical impact and course of major bleeding with edoxaban versus vitamin K antagonists

Thrombosis and Haemostasis

Analysis of major bleeding events from Hokusai-VTE study (n=8240) suggests edoxaban associated major bleeding events have similar presentation/course compared to those with vitamin K antagonist (56 and 65 events, respectively) in patients treated for venous thromboembolism.


Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study

British Medical Journal

This study (n=5,443,916) found that for the same dose of oestrogen, desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial thromboembolism compared with levonorgestrel.


Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

New England Journal of Medicine

This open label study (n=3310) in mainly Asian patients low-dose alteplase (tPA) did not show non-inferior to standard-dose tPA with respect to death and disability at 90 days. There were significantly fewer symptomatic intracerebral haemorrhages with low-dose tPA.


Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack

New England Journal of Medicine

This RCT (n=13,199) found that ticagrelor was not superior to aspirin in reducing the rate of stroke, myocardial infarction or death at 90 days (HR=0.89, 95%CI= 0.78-1.01, p=0.07).


Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial

The Lancet

In this open label trial (n=190) the odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted OR 2•05, 95% CI 1•18–3•56).


Systematic review of prognostic models for recurrent venous thromboembolism (VTE) post-treatment of first unprovoked VTE

BMJ Open

This review identified 3 models, HERDOO2 score, Vienna prediction model and DASH score, for predicting the recurrence risk of VTE and concluded that none of these can be considered ready for use until further external, robust validation is performed in new data.



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Effect of compression stockings on post thrombotic syndrome in patients with deep vein thrombosis: a meta-analysis of randomised controlled trials

The Lancet Haematology

Meta-analysis of 6 RCTs (n=1462) found use of elastic compression stockings in patients with DVT does not significantly reduce development of post thrombotic syndrome, however current body of evidence is limited, and further studies are needed to establish role of this therapy.



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Antithrombin for the prevention of intraventricular hemorrhage in very preterm infants

Cochrane Database of Systematic Reviews

Administration of antithrombin seems not to reduce incidence/severity of intraventricular haemorrhage in very preterm infants. Limited evidence is available on other clinically relevant outcomes. Given imprecision of estimate, this review cannot provide definitive answer.


Anticoagulants (extended duration) for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

Cochrane Database of Systematic Reviews

Moderate quality evidence suggests extended-duration anticoagulants to prevent VTE should be considered for people undergoing hip replacement surgery, although the benefit should be weighed against the increased risk of minor bleeding.


The left atrial appendage: from embryology to prevention of thromboembolism

European Heart Journal

This article describes the anatomy and function of the left atrial appendage (LAA) and current imaging tools for the identification of anatomical varieties. It also covers pathogenetic mechanisms of LAA thrombosis in AF patients, and examines the evidence on treatment strategies.


Insights from the NHS: the adoption of self monitoring coagulation status using point of care coagulometers (the CoaguChek XS system and the INRatio2 PT/INR monitor) for atrial fibrillation and heart valve disease

County Durham and Darlington NHS Foundation Trust

This shared learning guide presents a care pathway for the INR self-testing service, including the protocol for patient selection and training and the specification for the Health Call INR service, developed by clinicians working in the anticoagulation clinic.



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Pre-treatment with P2Y12 inhibitors in ACS patients: who, when, why, and which agent?

European Heart Journal

This review evaluates the available evidence on the value of pre-treatment with oral and intravenous P2Y12 inhibitors (clopidogrel, ticagrelor, prasugrel, and cangrelor) that can be administered to patients in whom coronary angiography followed by a possible PCI is planned.


Endovascular treatment versus medical care alone for ischaemic stroke: systematic review and meta-analysis

British Medical Journal

This review (10 RCTs) shows that in selected patients, endovascular treatment given within 6-8hrs after ischaemic stroke involving large vessels leads to improved functional outcome at 90 days without increased mortality vs medical care alone.


Risk of Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis in Patients With Acute Ischemic Stroke and High Cerebral Microbleed Burden: A Meta-analysis

JAMA Neurology

This meta-analysis (9 studies; 2479 patients) shows that high cerebral microbleed (CMB) burden on pretreatment MRI is independently associated with symptomatic intracerebral haemorrhage in patients with acute ischaemic stroke treated with iv thrombolysis.



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Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task Force

Annals of Internal Medicine

This systematic review concluded that consideration of the safety of primary prevention with aspirin requires an individualized assessment of aspirin's effects on bleeding risks and expected benefits because absolute bleeding risk may vary considerably by patient.


Aspirin for the Prevention of Cancer Incidence and Mortality: Systematic Evidence Reviews for the U.S. Preventive Services Task Force

Annals of Internal Medicine

In CVD primary and secondary prevention trials, aspirin reduced both 20-year colorectal cancer (CRC) mortality (n= 14033) and CRC incidence 10 to 19 years after initiation. (n=47464) (RR, 0.67 [CI, 0.52 to 0.86] and 0.60 [CI, 0.47 to 0.76], respectively).


Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force

Annals of Internal Medicine

This updated systematic review (11 RCTs) found a beneficial effect of aspirin (including at doses of 100mg or less per day) in reducing nonfatal MI
(absolute risk reduction, 0.15 to 1.43 events per 1000 person-years). Older adults seem to achieve a greater relative MI benefit.


The ‘obesity paradox’ in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial

European Heart Journal

This analysis (n=17913) found that in patients with AF treated with oral anticoagulants, higher BMI was associated with a lower risk of all-cause
mortality vs. normal BMI [overweight: HR 0.67 (95% CI 0.59–0.78); obese: HR 0.63 (95% CI 0.54–0.74), P < 0.0001].


Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial

The Lancet Neurology

Study (n=50) found proportion of patients with INR ≤1.2 within 3 hours of treatment initiation was achieved in 9 vs. 67% of patients given fresh frozen plasma and prothrombin complex concentrate, respectively (p=0•0003). The trial was stopped because of safety concerns.


COMP recommends Alprolix (eftrenonacog alfa) maintains Orphan Designation for treatment of Haemophilia B in EU

Biospace Inc.

Alprolix® (eftrenonacog alfa), is a recombinant factor IX Fc fusion protein therapy for the treatment of haemophilia B. An application for marketing authorisation was submitted in EU in June 2015. The COMP's recommendation is now referred to the EC.


Should Patients With Atrial Fibrillation and 1 Stroke Risk Factor (CHA2DS2-VASc Score 1 in Men, 2 in Women) Be Anticoagulated? Yes: Even 1 Stroke Risk Factor Confers a Real Risk of Stroke


This article compares the different stroke stratification schemes, highlighting interpretation difficulties and pitfalls as well as assessing the net benefit of stroke prophylactic treatment vs. alternative treatments.


Stroke prevention in atrial fibrillation in patients with Chronic Kidney Disease (CKD)


This article presents a case of a 68 year old woman with hypertension, diabetes and congestive heart failure presenting with palpitations. It assesses stroke risk and looks at different options for anticoagulation in CKD.




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Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54

European Heart Journal

The benefit of ticagrelor for long-term secondary prevention in patients with prior MI and ≥1 additional risk factor appeared more marked in patients continuing on or re-starting after only a brief interruption of P2Y12 inhibitors, compared with patients off them for > 1 year.


The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study

The Lancet

The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) score performed better than HAS-BLED and ORBIT scores in patients with AF on anticoagulants from the ARISTOTLE and RE-LY trials.


Indiscriminate Testing for Heparin-Induced Thrombocytopenia: A Teachable Moment

JAMA Internal Medicine

This case report illustrates the ramifications of overtesting, and advises that it is crucial to consider other causes of thrombocytopenia and determine pretest probability to guide management whenever heparin-induced thrombocytopenia is suspected.



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