Revised SPCs: Xarelto (rivaroxaban)

electronic Medicines compendium

SPC revised to include a new indication; co-administration with acetylsalicylic acid for the prevention of atherothrombotic events in adult patients with coronary artery disease or symptomatic peripheral artery disease at high risk of ischaemic events.

 

Hydroxycarbamide Plus Aspirin Versus Aspirin Alone in Patients With Essential Thrombocythemia Age 40 to 59 Years Without High-Risk Features

Journal of Clinical Oncology

RCT (n=2,373) reports preemptive addition of hydroxycarbamide to aspirin did not reduce vascular events (VE) and incidence of significant VE was low (0.93 per 100 patient-years [95% CI, 0.61 to 1.41)]). If platelet count is < 1,500 × 109/L cytoreductive therapy is not indicated.

 

Conference report: Real-world evidence from Global Anticoagulant Registry (GARFIELD-AF) following study of non-vitamin K Antagonists oral anticoagulants (NOACs) vs. vitamin K antagonists (VKAs) in newly diagnosed atrial fibrillation

Biospace Inc.

A new analysis (n=19,134) found 19% fewer deaths in patients initiated on NOACs than VKAs at the time of diagnosis of AF (aHR 0.81 [95% CI 0.71- 0.92]; p<0.001).

 

Antifibrinolytics for heavy menstrual bleeding

Cochrane Database of Systematic Reviews

Review of 13 RCTs (n=1312) found antifibrinolytics (such as tranexamic acid) appears effective for treating heavy menstrual bleeding vs. placebo, NSAIDs, oral luteal progestogens, ethamsylate, or herbal remedies, but may be less effective than levonorgestrel intrauterine system.

 

Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus

New England Journal of Medicine

RCT (n=15,480) found aspirin prevented serious vascular events in diabetic patients and no CVD (8.5 v. 9.6%; rate ratio 0.88; 95% CI, 0.79-0.97; p=0.01) but also caused major bleeding (4.1 v 3.2% 1.29; 1.09-1.52; p=0.003); absolute benefits were outweighed by bleeding hazard.

 

Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness

New England Journal of Medicine

RCT (n=12,024) found rivaroxaban given to medical patients for 45 days after hospital discharge was not linked to a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo (0.83% rivaroxaban vs. 1.10% placebo; p=0.14).

 

Rivaroxaban in Patients with Heart Failure, Sinus Rhythm, and Coronary Disease

New England Journal of Medicine

RCT (n=5022) found rivaroxaban 2.5mg twice daily was not linked to significantly lower rate of death, myocardial infarction, or stroke than placebo among patients with worsening chronic heart failure, reduced left ventricular ejection fraction, coronary artery disease, and no AF.

 

Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent

The Lancet

RCT (n=15,968) found ticagrelor (TC) plus aspirin for 1 month followed by TC alone for 23 months was not superior to 12 months of standard dual antiplatelets followed by 12 months of aspirin alone in prevention of all-cause mortality or new Q-wave MI 2 years after PCI.

 

US FDA approves Jivi (recombinant factor VIII concentrate) for haemophilia A

Biospace Inc.

It has been approved for use in previously treated adults and adolescents (≥12 years) for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes.

 

 

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

 

Tranexamic Acid for the Prevention of Blood Loss after Vaginal Delivery

New England Journal of Medicine

In women with vaginal delivery at 35+ weeks' gestation who received prophylactic oxytocin (n=3891), use of tranexamic acid (1g IV) was not associated with a statistically significant reduction in postpartum haemorrhage (8.1% v 9.8% placebo; RR 0.83; 95% CI 0.6-1.01).

 

Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary interventions: a European consensus document

European Heart Journal

This updated joint consensus document discusses the optimal antithrombotic therapy management of this patient group, considering new guidelines published since 2014, and the availability of new drugs, devices, and interventional techniques.

 

Interventions for implementation of thromboprophylaxis in hospitalized patients at risk for venous thromboembolism

Cochrane Database of Systematic Reviews

Review of 13 RCTs (n=35,997) found increased prescription of prophylaxis associated with alerts and multifaceted interventions, and increased prescription of appropriate prophylaxis linked to alerts. Analysis was underpowered to assess effect on mortality and safety outcomes.

 

Uterotonic agents for preventing postpartum haemorrhage: a network meta‐analysis

Cochrane Database of Systematic Reviews

Analysis of 140 RCTs (n=88,947) found ergometrine (EG) + oxytocin (OX) combination, carbetocin, and misoprostol + OX were more effective for preventing postpartum haemorrhage (PPH) ≥500 mL than current standard OX. EG +OX was more effective for preventing PPH ≥1000 mL than OX.

 

Haemostatic therapies for acute spontaneous intracerebral haemorrhage

Cochrane Database of Systematic Reviews

Review of 12 RCTs (n=1732) was unable to draw firm conclusions about efficacy and safety of antifibrinolytic drugs for acute spontaneous intracerebral haemorrhage (ICH), and clotting factors vs. fresh frozen plasma for acute spontaneous ICH associated with anticoagulant drug use.

 

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

 

Revised SPC: NovoEight (human coagulation factor VIII) powder and solvent for solution for injection (all strengths)

electronic Medicines compendium

Information has been added on weight based dosing as has warning that in patients with existing CV risk factors, substitiution therapy with FVIII may increase CV risk. ADR data from trial in treatment naïve patients, aged 0 to 6 years have been added.

 

Revised SPC: Xarelto (rivaroxaban) 2.5 mg film-coated tablets

electronic Medicines compendium

DRESS syndrome and anaphylactic reactions have been added to SPC as adverse effects. SPC has been amended to advise interaction with fluconazole/erythromycin/clarythromycin is likely not clinically relevant in most patients but can be potentially significant in high-risk patients.

 

Association of Intracranial Hemorrhage Risk With Non–Vitamin K Antagonist Oral Anticoagulant Use vs Aspirin Use: A Systematic Review and Meta-Analysis

JAMA Neurology

Review of 5 RCTS (n=39,398) found 15 to 20mg dose of rivaroxaban (RV) once daily is linked to increased risks of intracranial haemorrhage vs. aspirin (2 trials; OR, 3.31; 95% CI, 1.42-7.72), while smaller daily doses of RV and apixaban were not, suggesting dose dependent risk.

 

Revised SPC: Eliquis (apixaban) 2.5 mg film-coated tablets

electronic Medicines compendium

The SPC has been updated to advise that care should be taken if patients are treated concomitantly with SSRIs or SNRIs, due to the increased bleeding risk.

 

Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE‐2)

British Journal of Surgery

RCT (n=10,010) found that perioperative withdrawal of chronic aspirin therapy did not increase cardiovascular or vascular occlusive complications (HR for death or MI = 1.48, 95% CI 0.71-3.09 for aneurysm repair and 1.16, 0.62-2.17 for surgery for occlusive vascular disease).

 

 

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

 

Revised SPC: Brilique (ticagrelor) products

electronic Medicines compendium

Timing of discontinuation of ticagrelor prior to elective surgery has been changed from 7 to 5 days.

 

Management of Intraprocedural Anticoagulation in Patients on Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Catheter Ablation for Atrial Fibrillation

Circulation

This review aims to provide a brief summary on physiology of haemostasis, review key studies on DOAC safety and efficacy in AF catheter ablation, and identify current gaps in knowledge on intraprocedural anticoagulation and monitoring.

 

 

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

A systematic review of the efficacy of aspirin monotherapy versus other antiplatelet therapy regimens in peripheral arterial disease

Journal of Vascular Surgery

Review of 14 studies (10 RCTs) found that dual antiplatelet therapy (DAPT) reduces rates of major adverse cardiac events, major adverse cardiac and cerebrovascular events, and mortality compared with use of mono APT after revascularisation in peripheral arterial disease.

 

Rates of Overtreatment and Treatment-Related Adverse Effects Among Patients With Subsegmental Pulmonary Embolism

JAMA Internal Medicine

Restrospective review (single centre, n=1,408) found that almost all isolated subsegmental pulmonary embolisms (SSPEs) were anticoagulated with a similar frequency to more proximal embolisms and that treatment was associated with harm (e.g. bleeding).

 

Antithrombotic Therapy in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Undergoing Percutaneous Coronary Intervention: A North American Perspective–2018 Update

Circulation

On the basis of pivotal clinical trials this group recommended that a DOAC be preferred over a vitamin K antagonist as the oral anticoagulant of choice. This document provides a focused update on the rationale for the new expert consensus–derived recommendations.

 

CHMP negative opinion: Dexxience (betrixaban) for the prevention of venous thromboembolism

European Medicines Agency

A previous negative opinion was confirmed after re-examination. The CHMP considered that the study did not satisfactorily show efficacy when used for preventing blood clots in patients admitted to hospital for recent medical illness. Also, those given betrixaban had more bleeding.

 

CHMP positive opinion: Xarelto (rivaroxaban) licence extension

European Medicines Agency

The license extension is for use (as 2.5mg tablets in combination with aspirin) for the prevention of atherothrombotic events in adult patients with coronary artery disease or symptomatic peripheral artery disease at high risk of ischaemic events.

 

 

 

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

Aspirin Plus Clopidogrel vs Aspirin Alone for Preventing Cardiovascular Events Among Patients at High Risk for Cardiovascular Events

Journal of the American Medical Association

Based on a Cochrane review of 15 trials it is concluded that for every 1000 patients treated for about 10 months with the combination instead of aspirin alone there will be 13 and 23 fewer cases of MI and stroke respectively but 9 additional cases of major bleeding.

 

Variation in anticoagulation for atrial fibrillation between English clinical commissioning groups: an observational study

British Journal of General Practice

Analysis of data from the national Quality and Outcomes Framework showed that the percentage of patients prescribed anticoagulants for atrial fibrillation increased from 65.1% to 77.9% between 2012/13 and 2015/16 but 9 out of 10 CCGs still do not achieve 90% anticoagulation.

 

Revised SPC: Revolade (eltrombopag) tablets

electronic Medicines compendium

Eltrombopag is highly coloured and so has the potential to interfere with some laboratory tests eg total bilirubin and creatinine testing. If the laboratory results and clinical observations are inconsistent, re-testing using another method is advised.

 

Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for management of cryptogenic stroke?

British Medical Journal

Review (7 RCTs; n=3913) found that patent foramen ovale closure prevents recurrent stroke relative to antiplatelet therapy, but not anticoagulants, and is associated with procedural complications and persistent atrial fibrillation in adults aged <60 years with cryptogenic stroke.

 

Continued vs. interrupted direct oral anticoagulants at the time of device surgery, in patients with moderate to high risk of arterial thrombo-embolic events (BRUISE CONTROL-2)

European Heart Journal

RCT (n=662) found that either continued or interrupted direct oral anticoagulants (dabigatran, rivaroxaban, or apixaban) was a reasonable management strategy at the time of device surgery (primary outcome of clinically significant haematoma occurred in 2.1% of both arms; p=0.97).

 

Andexxa—An Antidote for Apixaban and Rivaroxaban

Journal of the American Medical Association

This Medical Letter review discusses the mechanism of action, adverse effects, and cost associated with coagulation factor Xa that was approved by the FDA for reversal of the anticoagulant effect of apixaban and rivaroxaban.

 

 

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

Revised SPC: Xarelto (rivaroxaban) tablets - all strengths

electronic Medicines compendium

DRESS syndrome (Drug reaction with eosinophilia and systemic symptoms) noted in post-marketing reports (frequency very rare). Interaction with fluconazole/ erythromycin/clarythromycin not clinically relevant in most patients but potentially significant in high-risk patients.

 

Eltrombopag (Revolade): reports of interference with bilirubin and creatinine test results

Medicines and Healthcare products Regulatory Agency

Eltrombopag can cause serum discolouration and interference with the test results of creatinine and bilirubin. If these laboratory results are inconsistent with clinical observations, request re-testing using another method to determine the validity of the result.

 

Fatal or Irreversible Bleeding and Ischemic Events With Rivaroxaban in Acute Coronary Syndrome

Journal of the American College of Cardiology

Review of ATLAS ACS 2-TIMI 51 trial found that addition of rivaroxaban 2.5mg bd to aspirin and clopidogrel/ticlodipine was associated with 105 (95% CI 6-204) fewer fatal or irreversible events (including ischaemic and haemorrhagic events), per 10,000 patient years vs dual therapy.

 

 

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 therapy in patients with stroke and atrial fibrillation: a registry-based study of acute stroke care in Surrey, UK

BMJ Open

Study (n=3309) found that atrial fibrillation (AF) occurred more frequently in patients admitted with recurrent (30.2%) vs first stroke (17.1%). Of 666 (20.1%) patients with history of AF, 45.3% were anticoagulated, 41.9% untreated and 12.8% deemed unsuitable for anticoagulation.

 

Anticoagulation and Antiplatelet Strategies After On-X Mechanical Aortic Valve Replacement

Journal of the American College of Cardiology

RCT (n=576) found, that for low thrombotic risk patients, dual antiplatelet therapy had higher rates of thromboembolism vs warfarin plus aspirin (3.12% vs 0.29% per patient/year, p=0.02).

 

Effect of Alteplase vs Aspirin on Functional Outcome for Patients With Acute Ischemic Stroke and Minor Nondisabling Neurologic Deficits: The PRISMS Randomized Clinical Trial

Journal of the American Medical Association

RCT (n=313) found that in those with non-disabling stroke, treatment with alteplase did not increase the likelihood of favourable functional outcome at 90 days vs aspirin. Symptomatic intracranial haemorrhage was more common with alteplase (3.2% vs 0%, p<0.05).

 

New product: AROVI (enoxaparin biosimilar) pre-filled syringes with safety device

electronic Medicines compendium

This enoxaparin biosimilar comes as 2,000 IU (20mg/0.2ml), 4,000 IU (40mg/0.4ml), 6,000 IU (60mg/0.6ml), 8,000 IU (80mg/0.8ml), 10,000 IU (100mg/1ml), 12,000 IU (120mg/0.8ml) and 15,000 IU (150mg/1ml) pre-filled syringes with safety device.

 

Clinical Commissioning Policy: Emicizumab as prophylaxis in people with congenital haemophilia A with factor VIII inhibitors (all ages)

NHS England

NHS England will routinely commission this specialised treatment. The arrangements and criteria for funding of this treatment for the population in England is outlined in this policy document.

 

Clinical Commissioning Policy: Susoctocog alfa for treating bleeding episodes in people with acquired haemophilia A (all ages)

NHS England

NHS England will routinely commission this specialised treatment. The arrangements and criteria for funding of this treatment for the population in England is outlined in this policy document.

 

Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease

Heart

Analysis (n=14,793) found in anticoagulated AF patients, aortic stenosis (AS) is linked to higher risk of stroke/systemic embolism, bleeding/death. Efficacy and safety benefits of apixaban vs. warfarin were consistent regardless of presence of mitral/aortic regurgitation or AS.

 

Prevalence and treatment of atrial fibrillation in UK general practice from 2000 to 2016

Heart

17 sequential cross-sectional analyses found prevalence of recorded AF has increased from 2000 to 2016 (2.14 to 3.29%); anticoagulation of eligible patients with AF has more than doubled (35.4 to 75.5% in high stroke risk group), alongside decrease in use in ineligible patients.

 

Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials

The Lancet

Analysis of 10 trials of aspirin in primary prevention (n=117,279) found low doses (75–100mg) were only effective in preventing vascular events in patients weighing <70kg, and had no benefit in 80% men and~ 50% women ≥70kg. Higher doses were only effective in patients ≥70kg.

 

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

Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care

British Medical Journal

Trial (n=132 231 warfarin [WF],7744 dabigatran,37 863 rivaroxaban [RV],18 223 apixaban [AP] users) found AP to be safest drug with reduced risks of major, intracranial and GI bleeding vs. WF. RV and low dose AP were, however, linked to increased risks of all-cause mortality.

 

Variation in anticoagulation for atrial fibrillation between English clinical commissioning groups: an observational study

British Journal of General Practice

This study found the proportion of eligible AF patients prescribed anticoagulants improved from 65.1% in 2012/2013 to 77.9% in 2015/2016, with considerable increases in the eligible population as a result of decreased exception reporting and the use of the CHA2DS2VASc score.

 

 

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

Outcomes Associated with Apixaban Use in End-Stage Kidney Disease Patients with Atrial Fibrillation in the United States

Circulation

Retrospective cohort study (n=2351 on apixaban; 23,172 on warfarin) found apixaban use may be linked to lower risk of major bleeding vs. warfarin (HR 0.72, 95% CI 0.59-0.87; P<0.001) with standard 5mg BD dose also linked to reductions in thromboembolic and mortality 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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

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