Continuation versus discontinuation of antiplatelet therapy for bleeding and ischaemic events in adults undergoing non‐cardiac surgery

Cochrane Database of Systematic Reviews

Review of 5 RCTs (n=666) found low‐certainty evidence that either continuation or discontinuation of antiplatelet therapy before non‐cardiac surgery may make little or no difference to mortality, bleeding requiring surgical intervention, or ischaemic events.

Healthcare professional letter: Actilyse (Alteplase) in Acute lschaemic Stroke: Important information on extension to use in adolescents and request for data collection

Boehringer Ingelheim

Following the recent license extension of Actilyse® (alteplase) to include adolescents of 16-17 years in the acute ischaemic stroke indication, Boehringer Ingelheim is requesting collection of further data on safety and efficacy in this population.

A systematic review of clinicians' views and experiences of direct‐acting oral anticoagulants in the management of nonvalvular atrial fibrillation

British Journal of Clinical Pharmacology

Review of 10 studies notes in studies reporting clinician preference, DOACs were 1st choice over warfarin in naïve patients based on perceptions of evidence of effectiveness equivalent/superior to warfarin and superior safety. There were concerns about managing over-anticoagulation.

Effect of Variation in Published Stroke Rates on the Net Clinical Benefit of Anticoagulation for Atrial Fibrillation

Annals of Internal Medicine

Markov model decision analysis (n=33,434) with warfarin as base case, and DOACs modeled in secondary analysis found variation in published AF stroke rates for patients not on anticoagulants results in multifold variation in net clinical benefit of anticoagulation.

An Open-Label Randomized Trial Comparing Oral Anticoagulation with and without Single Antiplatelet Therapy in Patients with Atrial Fibrillation and Stable Coronary Artery Disease Beyond One Year after Coronary Stent Implantation: The OAC-ALONE Study

Circulation

RCT prematurely terminated after enrolling 696 patients in 38 months did not establish non-inferiority of oral anticoagulation (OAC) alone to combined OAC and antiplatelet therapy in patients with AF and stable coronary artery disease beyond 1 year after stenting.

Improved Stroke Prevention in Atrial Fibrillation After the Introduction of Non–Vitamin K Antagonist Oral Anticoagulants

Stroke

Analysis of pharmacy claims data found increased oral anticoagulant use (from 51.6% to 73.8%) contributed to marked reduction of ischaemic strokes (2.01/100 person-years in 2012 to 1.17 in 2017; incidence rate ratio, 0.58; 95% CI, 0.52–0.65) without increasing bleeding rates.

Non–Vitamin K Antagonist Oral Anticoagulants for Mechanical Heart Valves: Is the Door Still Open?

Circulation

Mechanical valves currently pose absolute contraindication to DOACs based on results of single phase II study (RE-ALIGN). Article calls on several aspects of both preclinical studies and RE-ALIGN to be critically re-evaluated to identify patients most likely to benefit from DOACs.

AF screening: who is calling the tune?

Drug and Therapeutics Bulletin

Editorial highlights need to recognise gaps in evidence for population screening (PS), uncertainty over harm:benefit ratio of anticoagulation in people at lower risk, impact of labelling people with AF diagnosis, and guard against industry-led incremental drift to widespread PS.

Vorapaxar for HIV-associated inflammation and coagulopathy (ADVICE): a randomised, double-blind, placebo-controlled trial

The Lancet

This RCT (n=65) demonstrated that vorapaxar, a licensed inhibitor of proteinase activated receptor-1, had no effect on D-dimer concentrations in HIV-infected patients receiving stable antiretroviral therapy but at risk of poor outcomes.

Antifibrinolytic therapy for preventing oral bleeding in people on anticoagulants undergoing minor oral surgery or dental extractions

Cochrane Database of Systematic Reviews

There were no eligible trials in people on continuous DOAC treatment. For vitamin K antagonists (4 studies; n=253) there seems to be a beneficial effect of locally applied tranexamic acid; however definitive conclusions cannot be made due to limitations of the evidence.

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

Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia

Gastroenterology

The ADAPT-1 and ADAPT-2 RCTs reported superiority of avatrombopag vs placebo in reducing need for platelet transfusions or rescue procedures for bleeding in patients with thrombocytopenia and chronic liver disease undergoing a scheduled procedure.

Anticoagulation for the long‐term treatment of venous thromboembolism in people with cancer

Cochrane Database of Systematic Reviews

Review of 16 RCTs (n= 5167) found evidence showing that low molecular weight heparins (LMWHs) vs. vitamin K antagonists probably produces an important reduction in venous thromboembolism (VTE); and DOACs vs. LMWH, may likely reduce VTE but may increase risk of major bleeding.

Long-Term Risk of Venous Thromboembolism in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Journal of Clinical Oncology

Study reports childhood cancer survivors are at increased risk for VTE across their lifespan and a diagnosis of VTE increases mortality risk. Late VTE incidence among survivors and siblings was 1.1 and 0.5 events /1000 person-years, respectively (RR, 2.2; 95% CI, 1.7 to 2.8).

Effect of Aspirin on All-Cause Mortality in the Healthy Elderly

New England Journal of Medicine

RCT (n=19,114) found an increased risk of death from any cause for aspirin vs placebo (12.7 vs 11.1 events/1000 person-years, HR 1.14, 95% CI 1.01-1.29). Cancer was the major contributor to higher mortality with aspirin accounting for 1.6 excess deaths/1000 person-years.

Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly

New England Journal of Medicine

RCT (n=19,114) found no difference in rate of cardiovascular disease for aspirin vs placebo (10.7 vs 11.3 events/1000 person-years, HR 0.95, 95% CI 0.83-1.08). Major haemorrhage was more common with aspirin (8.6 vs 6.2 events/1000 person years, 1.38, 1.18-1.62).

Effect of Aspirin on Disability-free Survival in the Healthy Elderly

New England Journal of Medicine

RCT (n=19,114) found no difference in the composite rate of death, dementia and persistent physical disability for aspirin vs placebo (21.5 vs 21.2 events/1000 person-years, HR 1.01, 95% CI 0.92-1.11). Major haemorrhage was more common with aspirin (3.8% vs 2.8%, 1.38, 1.18-1.62).

Coagulation Test Interpretation in a Patient Taking Direct Oral Anticoagulant Therapy

Journal of the American Medical Association

This short review, in the form of a case vignette, highlights that DOAC-specific coagulation tests such as anti-Xa assay and dilute thrombin time may help guide clinical decisions in bleeding patients or in those requiring urgent surgery. Time of last dose needs to be considered.

Prothrombin Complex Concentrates for Perioperative Vitamin K Antagonist and Non–vitamin K Anticoagulant Reversal

Anesthesiology

Review found concentrate was consistently shown to reduce INR rapidly and control bleeding effectively. In studies vs. plasma, it was linked to more patients achieving target INRs rapidly, with improved haemostasis, and no differences in thromboembolic event rates were seen.

Antithrombotic treatment is associated with intraplaque haemorrhage in the atherosclerotic carotid artery: a cross-sectional analysis of The Rotterdam Study

European Heart Journal

In a large population-based sample of individuals with subclinical carotid atherosclerosis, current and past use of antithrombotics was linked to intraplaque haemorrhage (IPH) in carotid artery plaques. Longer duration of use and higher doses were linked higher frequency of IPH.

Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial

The Lancet

RCT (n=12,546; EC aspirin 100mg/d vs. placebo) found event rate was much lower than expected, making study more representative of a low-risk population, and role of aspirin in primary prevention could therefore not be addressed in patients at moderate risk of CVD.

European CHMP recommends granting of marketing authorisation for damoctocog alfa pegol (Jivi) for treatment of haemophilia A (congenital factor VIII deficiency)

European Medicines Agency

Damoctocog is a recombinant human factor VIII which replaces the missing coagulation factor VIII needed for effective haemostasis. It will be available as powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, 2000 IU and 3000 IU).

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

Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation

Heart

Biomarker substudy (n=4850) suggests in situation without acute increased coagulation activity (e.g AF), apixaban reduces coagulation markers D-dimer and fragment 1+2  to lower degree vs. warfarin, which seems enough to protect against stroke without increasing bleeding risk.

Aspirin-Exacerbated Respiratory Disease

New England Journal of Medicine

Review covers atopic diseases, COX-1 inhibitor reactions, medical history, prevalence, non-aspirin-exacerbated respiratory disease, NSAID hypersensitivity, pathological and pharmacopathological features, medical/surgical treatment, aspirin (AS) desensitisation and AS treatment.

Anticoagulation for people with cancer and central venous catheters

Cochrane Database of Systematic Reviews

This review (13 RCTs; n=3420) found moderate-certainty evidence that LMWH reduces catheter‐related venous thromboembolism (CR-VTE); evidence was inconclusive for LMWH effects on mortality and effects of vitamin K antagonists (VKA) on mortality or CR-VTE, and for LMWH versus VKA.

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

Venous thromboembolism (VTE) risk assessment: Q1 2018/19

NHS Improvement

This reports details the official statistics for venous thromboembolism (VTE) risk assessment in England for providers for quarter 1 2018/19 (April to June 2018).

What is the evidence for the use of Low Molecular Weight Heparins for the prophylaxis of travel-related thrombosis?

Specialist Pharmacy Service

Q+A notes none are specifically licensed for this use and good evidence is lacking, however, benefit of anticoagulant prophylaxis may outweigh risks in those at high risk of developing thromboses during a long haul flight; this use has been suggested by several national bodies.

Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: the TARDIS RCT

National Institute for Health Research

Trial that was stopped early (n=3096) found use of 3 antiplatelets (intensive: aspirin [AS], clopidogrel, [CP], dipyridamole [DP]) is linked to increased bleeding without significant reduction in recurrence of stroke/TIA vs. guideline antiplatelet agents (AS and DP, or CP alone).

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 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