Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation

JAMA Internal Medicine

This analysis of 118 891 atrial fibrillation patients taking rivaroxabanor dabigatran reports that those treated with rivaroxaban were more likely to experience both intracranial haemorrhage or major extracranial bleeding than those treated with dabigatran.


The Handbook of Perioperative Medicines

UK Clinical Pharmacy Association

This handbook, in the form of drug monographs, contains information on how medicines are to be managed in the peri-operative period. It has been developed collaboratively by clinical pharmacy experts, to address the need for a national guidance for healthcare professionals.


International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer

The Lancet Oncology

In this review, the authors provide the first evidence-based international guidelines on direct oral anticoagulant use in the treatment of VTE. These guidelines
aim to address in-hospital and outpatient cancer-associated VTE in specific subgroups of patients with cancer.


Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials

The Lancet

Review of 8 RCTs (n=963) found that low-molecular-weight heparin (LMWH) does not seem to reduce risk of recurrent placenta-mediated pregnancy complications vs. no LMWH in at-risk women. However some decreases in event rates might have been too small for power of study to explore.



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:

Early real-world evidence of persistence on oral anticoagulants for stroke prevention in non-valvular atrial fibrillation: a cohort study in UK primary care


Study (n=15,242) found observed differential prescribing of oral anticoagulants (OACs) can result in channeling bias in comparative effectiveness research.
Persistence patterns changed over follow-up time, apixaban had improved persistence rates vs. other OACs.


Management and outcomes of vaginal bleeding and heavy menstrual bleeding in women of reproductive age on direct oral anti-factor Xa inhibitor therapy: a case series

The Lancet Haematology

Study (n=57, with 72 vaginal bleeding events) found vaginal bleeding, particularly heavy menstrual bleeding, is a common complication in women of reproductive age on direct oral factor Xa inhibitor therapy. Most cases can be treated conservatively.


BMJ investigation finds manufacturer failed to disclose faulty device in ROCKET AF trial of rivaroxaban

British Medical Journal

Investigation found companies were aware of concerns about faulty INRatio device, which could have put participants at unnecessary risk. It asks whether regulatory investigations could have been avoided, who was informed, FDA's concerns, and whether trial results can be trusted.


Does tranexamic acid improve outcomes in traumatic brain injury?

British Medical Journal

Review notes efficacy/safety is uncertain, although RCTs are under way. It suggests intracranial bleeding could be reduced but risk of cerebral thrombosis and
ischaemia might increase with treatment. It does not support use in routine clinical practice unless RCTs show benefit.


Novel oral anticoagulants for atrial fibrillation

British Medical Journal

Editorial notes use has proved to be highly variable in patients most at risk, (4%-70% in different areas in England), which may partly be due to clinical
uncertainty about balance of benefit to harm, and which cannot be resolved until independent scrutiny of key trial data.


New oral anticoagulants for stroke prevention in atrial fibrillation: Infographic

Pharmaceutical Journal

This infographic covers the anticoagulant effect of these agents, the slow rise of prescribing, the individual agents, and deciding which one to prescribe.


Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomised controlled trial

British Medical Journal

RCT (n=7123) found a bivalirudin monotherapy strategy vs. heparin with or without glycoprotein IIb/IIIa inhibitors, did not result in reduced major adverse
cardiovascular events or net adverse clinical events in patients with or without ST segment elevation.


Valvular heart disease and pregnancy: management of prosthetic valves


This review discusses the pregnancy risks in women with prosthetic heart valves, strategies for anticoagulation in women with mechanical heart valves, and the management of complications.



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:

New Product: Kogenate Bayer powder (human coagulation factor VIII ) and solvent for solution for injection

electronic Medicines Compendium

This product is licensed for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). This preparation does
not contain von Willebrand factor and is therefore not indicated in von Willebrand's disease.


Revised SPC: Haemoctin (Human plasma derived coagulation factor VIII)

electronic Medicines Compendium

Special warning for use in patients with existing cardiovascular risk factors has been added, which states that substitution with factor VIII may increase the
cardiovascular risk.


Edoxaban drug–drug interactions with ketoconazole, erythromycin, and cyclosporine

British Journal of Clinical Pharmacology

Report of 3 drug-drug interaction studies notes administration of dual inhibitors of P-gp and CYP3A4 increased edoxaban exposure by less than two-fold. Effect
appears to be primarily due to P- gp inhibition and impact of CYP3A4 inhibition appears to be less pronounced.


A systematic review of tranexamic acid in hip fracture surgery

British Journal of Clinical Pharmacology

Analysis of 7 studies (n=770) found moderate quality evidence that tranexamic acid reduces blood transfusion in hip fracture surgery vs. placebo (RR: 0.54; 95% CI: 0.35–0.85), with low quality evidence suggesting no increased risk of thrombotic events.


Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation


This analysis (UK) of 39,670 newly diagnosed AF patients showed that since NOACs were introduced, there has been an increase in patients receiving
guideline-recommended therapy, predominantly driven by increased use of NOACs and reduced use of other antithrombotics.



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:

Spontaneous subarachnoid haemorrhage

The Lancet

This article discusses pathophysiology, diagnosis, management, prognosis and prevention of this uncommon and severe subtype of stroke.



The Lancet

This seminar discusses the diagnosis, specific treatments for acute ischaemic and haemorrhagic stroke. It includes detail on recovery and rehabilitation, as
well as interventions under investigation and future directions.


idarucizumab (Praxbind)

Scottish Medicines Consortium

The SMC has accepted for use within NHS Scotland, idarucizumab (Praxbind®) for adults treated with dabigatran etexilate, when rapid reversal of its anticoagulanteffects is required for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding.



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:

Major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin: a “real-world” observational study in the United States

International Journal of Clinical Pharmacy

Retrospective cohort study (n=29,338) found among newly anticoagulated patients in real-world setting, initiation with rivaroxaban/warfarin was linked to
greater risk of major bleeding vs. initiation on apixaban. Additional observational studies are required to confirm findings.


Duration of Dual Antiplatelet Therapy: A Systematic Review for the 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease


This review of 11 RCTs (n=33,051) found strong evidence that prolonged dual anti-platelet therapy after implantation of newer-generation drug eluting
stents entails a tradeoff between reductions in stent thrombosis and MI and increases in major hemorrhage.


Warfarin treatment quality and prognosis in patients with mechanical heart valve prosthesis


This Swedish cohort study evaluating 18,022 patient-years on warfarin showed high INR variability (above ≥0.4) or lower time in therapeutic range (≤70%) was associated with higher risk of bleeding (rate per 100 years 4.33 vs 2.08, HR 2.15 and 5.13 vs 2.30, HR 2.43, respectively).



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:

Efficacy and safety of left atrial appendage closure versus medical treatment in atrial fibrillation: a network meta-analysis from randomised trials


Analysis of 19 RCTs (n=87,831) suggests procedure is superior to placebo and antiplatelets, and comparable to NOACs for preventing mortality and stroke/systemic embolism, with similar bleeding risk. However, wide confidence intervals for variables warrants cautious interpretation.


Peri-operative management of anticoagulation and antiplatelet therapy

British Committee for Standards in Haematology

Previous guideline on warfarin (2011) has been updated to include management of patients on direct oral anticoagulants and antiplatelet agents which are
becoming frequent clinical queries. This guideline considers whether and when such agents should be stopped and restarted.


Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy Study


Analysisof 11,643 patients noted that continued thienopyridine therapy reduced the rate of MI regardless of optimal medical therapy status and had consistent
effects on reduction in major adverse cardiovascular and cerebrovascular events and increased bleeding.


Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation: 5-year outcome in a randomised clinical trial


Pre-specified 5 year follow-up of 245 of 294 patients (83%) randomised to radiofrequency catheter ablation (RFA) or antiarrhythmic drug therapy (AAD) in MANTRA-PAF trial found that occurrence and burden of any AF and symptomatic AF were significantly lower in RFA group.


Net clinical benefit of warfarin in individuals with atrial fibrillation across stroke risk and across primary and secondary care


Cohort study (n=70,206 with AF in primary/secondary car, England 1998–2010) noted CHA2DS2-VASc accurately stratifies ischaemic stroke risk, but incidence rate at CHA2DS2-VASc=1 was lower than previously reported, which may change decision to start warfarin in this group.


Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors

New England Journal of Medicine

Descriptive preliminary analysis of study (n=67 with acute major bleeding within 18 hours after administration of factor Xa inhibitor), an initial bolus and subsequent 2-hour infusion of andexanet reduced anti–factor Xa activity, with effective haemostasis occurring in 79%.


Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial

The Lancet

In this RCT (n=877) assessing effect of platelet function monitoring with treatment adjustment vs no monitoring, the rate of occurrence of primary endpoint
(composite of CV death, MI, stroke, stent thrombosis, urgent revascularisation and bleeding) did not differ between groups.


Prevention of Stroke with Ticagrelor in Patients with Prior Myocardial Infarction: Insights from PEGASUS-TIMI 54


RCT (n=14,112) showed that addition of ticagrelor 60 mg bd to aspirin in patients with prior myocardial infarction significantly reduced the risk of stroke vs
placebo [HR 0.75 (0.57–0.98) p=0.034] without an excess of hemorrhagic stroke but with more major bleeding.


Edoxaban versus enoxaparin–warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial

The Lancet

This RCT (n=2199) showed rates of thromboembolism and major bleeding were low and similar in the 2 treatment groups and across different patient strata,
including those on reduced edoxaban dose due to renal impairment/bodyweight ≤60kg and on concomitant P-glycoprotein inhibitors.


Prasugrel versus Ticagrelor in Patients with Acute Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention: Multicenter Randomized PRAGUE-18 Study


In this RCT (n=1230) evaluating prasugrel v ticagrelor prior to PCI, no difference in occurrence of primary endpoint at 7 days (death, re-infarction, urgent target vessel revascularization, stroke, serious bleeding requiring transfusion or prolonging hospitalisation) was noted.


2016 ESC Guidelines for the management of atrial fibrillation

European Heart Journal

The European Society of Cardiology has issued guidance on the diagnosis and management of patients with atrial fibrillation.



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:




Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial

The Lancet Haematology

Results from this RCT (n=110) showed that rivaroxaban and warfarin both inhibit thrombin generation in patients with venous thromboembolism and
antiphospholipid syndrome, and rivaroxaban may be an effective alternative to warfarin in this group of patients.


Self‐monitoring and self‐management of oral anticoagulation

Cochrane Database of Systematic Reviews

Review found self-monitoring or self-management can improve quality of oral anticoagulation therapy and reduced thromboembolic events. A reduction in
all-cause mortality was observed in trials of self-management but not in self-monitoring, with no effects on major haemorrhage.


New perspectives on atrial fibrillation and stroke


The current stroke-prevention strategy in embolic and cryptogenic stroke starts with arrhythmia detection, followed by risk stratification and treatment for
those deemed to be at increased risk. This paper reviews recent findings that challenge this practice paradigm.


Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial

The Lancet Neurology

In this RCT of 410 patients comparing mechanical thrombectomy (MT) with standard iv thrombolysis (IVT) vs IVT alone, the addition of MT significantly improved functional independence in patients with acute cerebral ischaemia (p=0.028), with no evidence of increased mortality.


Andexanet Alfa, factor Xa inhibitor antidote, accepted for review by European Medicines Agency (EMA)

Biospace Inc.

The EMA's Committee for Medicinal Products for Human Use will now begin the centralized review procedure for andexanet alfa, a modified human Factor Xa molecule that acts as a decoy to target and sequester both oral and injectable Factor Xa inhibitors in the blood.



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:

Impact of Hemoglobin Levels and Anemia on Mortality in Acute Stroke: Analysis of UK Regional Registry Data, Systematic Review, and Meta‐Analysis

Journal of the American Heart Association

Combined data from cohort study (n=8013) and meta-analysis (20 trials) found anaemia on admission was linked to increased risk of mortality in both ischaemic stroke (OR 1.97; 95% CI 1.57–2.47) and haemorrhagic stroke (1.46; 1.23–1.74). Targeted interventions may improve outcomes.


Barriers to medication adherence for the secondary prevention of stroke: a qualitative interview study in primary care

British Journal of General Practice

28 survivors of stroke, including 14 accompanying caregivers and five GPs, were interviewed. Medication level barriers included beliefs about medication and
beliefs about how pills work, medication routines, changing medications, and regimen complexity and burden of treatment.


Pre-procedural dual antiplatelet therapy in patients undergoing transcatheter aortic valve implantation increases risk of bleeding


Japanese study (n=540) found dual antiplatelet therapy (DAPT) group had significantly higher incidence of any bleeding vs. single APT group (36.5% vs 27.5%, p=0.049) and no APT (36.5% vs 21.3%, p=0.010). The no APT group did not experience an increased risk of thrombotic events.


Lancet series on stroke prevention in atrial fibrillation

The Lancet

Lancet has published a clinical series of 3 papers on AF ahead of annual ESC meeting. AF is estimated to affect 33m people worldwide, but this is likely
underestimated since many do not know they have it until they develop symptoms or present with stroke/systemic thromboembolism.



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:

Ticagrelor for preventing atherothrombotic events after myocardial infarction: Appraisal consultation document

National Institute for Health and Care Excellence

DRAFT guidance supports use of ticagrelor 60mg, in combination with aspirin, as continuation therapy for preventing atherothrombotic events in people who
have a history of MI and a high risk of developing atherothrombotic events, only if certain criteria are met.


Sixteen-year nationwide trends in antithrombotic drug use in Denmark and its correlation with landmark studies


This paper provides nationwide data on long-term trends in antithrombotic use, noting it has doubled, mainly due to increased antiplatelet use and introduction of DOACs. Authors discuss how trends in use of individual drugs correlate with publication of landmark studies.


Occurrence of death and stroke in patients in 47 countries 1 year after presenting with atrial fibrillation: a cohort study

The Lancet

In this study evaluating 15,361 patients of whom 1758 (11%) died within 1 year, heart failure was the most common cause of death (30%) followed by stroke (8%). There were marked unexplained inter-regional variations in the occurrence of stroke and death.


Stability of International Normalized Ratios in Patients Taking Long-term Warfarin Therapy

Journal of the American Medical Association

Research letter describes a study of 3749 patients taking warfarin for atrial fibrillation which found that 26% had 80% or more INR values in the 2.0-3.0
range during the first 6 months. Of these patients, 34% continued to have stable INRs over the next 12 months.


Triple Oral Antithrombotic Therapy (TOAT) - A Teachable Moment

JAMA Internal Medicine

This review, based on a case vignette, discusses the use of TOAT, highlighting steps to reduce bleeding risk are advisable. These include prescribing a
proton pump inhibitor, using lower doses of antiplatelets, and avoiding high-potency P2Y12 inhibitors prasugrel and ticagrelor.


Comparison of Dabigatran versus Warfarin in Patients with Atrial Fibrillation and Valvular Heart Disease: The RE-LY Trial


This review of the RE-LY trial found that the presence of VHD (n=3,950) did not influence the comparison of dabigatran with warfarin in terms of major bleed
rates and stroke and systemic embolism rates for both the 110mg and 150mg doses.



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:

Self-monitoring and self-management of oral anticoagulation therapy

Cochrane Database of Systematic Reviews

Review of 28 RCTs (n=8,950) found a reduction in thromboembolic events in the pooled estimate of self-monitoring or self-management vs standard monitoring (HR, 0.58; 95%CI, 0.45-0.75). No reduction in all-cause mortality or incidence of major or minor haemorrhage was seen.


Economic burden of non-malignant blood disorders across Europe: a population-based cost study

The Lancet Haematology

Non-malignant disorders of the blood cost the 31 European countries €11 billion in 2012. Health-care costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for less than €1 billion (6%).


Heparin for the prevention of intraventricular haemorrhage in preterm infants

Cochrane Database of Systematic Reviews

There is very limited data on effect of prophylactic heparin on incidence and severity of intraventricular haemorrhage (IVH). Both the identified trials used
heparin in the context of maintaining umbilical line patency and not specifically to prevent germinal matrix IVH.


Impact of age on long-term anticoagulation and how gender and monitoring setting affect it: implications for decision making and patient management

British Journal of Clinical Pharmacology

Study (n=2094) found that frequency of warfarin dose changes and INR monitoring events declined until around age 67, then increased as patients got older.


Anticoagulation versus antiplatelet or no therapy in patients undergoing bioprosthetic valve implantation: a systematic review and meta-analysis


In a meta-analysis of 2 randomised and 12 observational studies, there was no benefit of adding a vitamin K antagonist (VKA) with regards to thromboembolism or mortality, versus antiplatelet /no therapy. However, use of a VKA was linked to increased risk of major bleeding.


Venous thromboembolism in medical patients during hospitalisation and 3 months after hospitalisation: a prospective observational study

BMJ Open

Australian study (n=986) found 54 (5.5%) developed venous thromboembolism (VTE), of which 25.9% (14/54) had detected VTE post-hospitalisation with increased risk if there was history of VTE, recent surgery and pulmonary conditions, suggesting potential role of thromboprophylaxis.


Evaluation of two new NICE indicators to help GPs and CCGs improve identification and management of atrial fibrillation (AF)

National Institute for Health and Care Excellence

In 2017, 30 UK GP practices will test these indicators. GPs will routinely test anyone >65 years for AF and assess how often someone with AF discusses treatment with GP. If these measures are found to improve AF identification/management, they could be rolled out in 2017/18.



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