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

Antithrombotic Therapy for Peripheral Artery Disease in 2018

Journal of the American Medical Association

This article, form the US perspective, reviews current evidence and makes recommendations on antithrombotic therapy in patients with or without ischaemic limb symptoms, as well as in patients with or without manifest coronary or cerebrovascular disease.

Can small volume intramuscular injections be given to patients taking oral anticoagulants?

Specialist Pharmacy Service

Q+A notes most of published studies relate to IM influenza vaccination in patients on older anticoagulants. Data are limited and some findings are contradictory. There is very little published information about the risks of adverse effects with DOACs and IM injections.

Venous thromboembolism after induced abortion: a population-based, propensity-score-matched cohort study in Canada

The Lancet Haematology

Study (n= 176,001 matched to 880,005 non-pregnant) found 42-day risk of venous thromboembolism after induced abortion is double that of matched non-pregnant woman (30.1 v. 13.5/100,000; HR 2.23, 95% CI, 1.61–3.08), but is significantly lower than after livebirth (0.16; 0.12–0.22).

Roche introduces CoaguChek Vantus system with built in Bluetooth® technology in US

Biospace Inc.

Roche says this is first self-testing device for coagulation monitoring with built in Bluetooth technology. Patients can use tablet/smartphone with compatible app to send results via wireless connectivity, enabling healthcare providers to receive patients' INR results.

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

Meta-Analysis of Studies Comparing Dual- Versus Mono-Antiplatelet Therapy Following Transcatheter Aortic Valve Implantation

American Journal of Cardiology

Analysis of 8 studies (n=2439) found dual antiplatelets (vs. mono) linked to increased risk at 30 days of all-cause mortality, major/life-threatening bleeding, and major vascular complications without decrease in ischaemic complications;at 6 months, excess bleeding risk persisted.

A clinical prediction model for cancer-associated venous thromboembolism: a development and validation study in two independent prospective cohorts

The Lancet Haematology

Data from CATS cohort (n=1423) were used to select prognostic variables for inclusion in clinical prediction model. Two in final model that were externally validated (tumour-site category/ D-dimer) predicted risk of venous thromboembolism in ambulatory patients with solid cancers.

Aspirin may be a follow-on option to prevent blood clots, starting five days after hip or knee surgery

National Institute for Health Research Signal

Expert commentary is provided for an RCT which found aspirin as effective as rivaroxaban at preventing VTE post hip or knee surgery. While there are implications for savings, the key message is that postoperative prophylaxis is the most important factor for attenuating VTE risk.

Gastrointestinal bleeding risk of selective serotonin reuptake inhibitors by level of kidney function: a population‐based cohort study

British Journal of Clinical Pharmacology

Cohort study (n=413,116) found an increasing adjusted rate difference of GI bleeding for SSRIs vs no SSRIs as kidney function deteriorated (2.0 events per 1000 person-years for no CKD vs 7.9 events per 1000 person-years for CKD stage 4/5, p-trend = 0.001).

Antithrombotic Therapy for Peripheral Artery Disease in 2018

Heart

This article reviews cardiovascular risk stratification of patients with peripheral artery disease and current standards of practice for use of antiplatelet and anticoagulant therapies.

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

electronic Medicines compendium

The SPC has been amended to state that 'apixaban can be initiated or continued in NVAF patients who may require cardioversion', and to include detail on dose in relation to cardioversion. Data from the EMANATE study (conducted in patients undergoing cardioversion) has been added.

Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial

The Lancet

In this study (n=1,754), the incidence of the primary composite endpoint was lower in those randomised to dabigatran 110mg BD (11% vs 15% with placebo; HR 0.72; 95% CI 0.55-0.93; p=0.0115), with no significant increase in major bleeding (3% v 4%; HR 0.92; 0.55-1.53; p=0.76).

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

Periprocedural Outcomes of Direct Oral Anticoagulants vs. Warfarin in Non-Valvular Atrial Fibrillation: A Meta-analysis of Phase III Trials

Circulation

Meta-analysis of sub-analysis of RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF trials found in short-term, safety/efficacy of DOACs and warfarin (WF) periprocedurally are not different. DOACs were linked to 38% lower risk of major bleeding vs. WF with uninterrupted anticoagulation.

Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation

Cochrane Database of Systematic Reviews

Review of 13 RCTs (n=67,688), most of which involved apixaban, edoxaban, rivaroxaban, found treatment with factor Xa inhibitors significantly reduced number of strokes and systemic embolic events vs. warfarin with AF; the absolute effect vs. warfarin was, however, rather small.

US FDA accepts supplemental biologics license application for prophylactic and paediatric use of Coagadex® (Coagulation Factor X, Human) for treatment of hereditary factor X deficiency

Biospace Inc.

Application relates to use in children under 12 years of age and is based on data from phase 3 prospective TEN02 study in children with moderate to severe deficiency. Coagadex is currently only licensed in UK for use in children over age of 12 years.

Data from Haven III and Haven IV trials suggest efficacy of emicizumab in haemophilia patients without factor VIII inhibitors

PharmaTimes

A 96% and 97% reduction in treated bleed were found in these studies respectively vs no prophylaxis. Emicizumab is currently licensed for routine prophylaxis of bleeding episodes in patients with haemophilia A with factor VIII inhibitors.

US FDA approves avatrombopag (Doptelet) for treatment of thrombocytopenia in patients with chronic liver scheduled to undergo a medical or dental procedure

Biospace Inc.

This thrombopoietin receptor agonist has been evaluated in ADAPT-1 /ADAPT-2 trials (n=435) which reported higher proportion of patients had increased platelet (PL) counts and did not require PL transfusion/rescue therapy on day of -and up to 7 days after procedure vs. placebo.

Use of Venous Thromboembolism Prophylaxis in Hospitalized Patients

JAMA Internal Medicine

Analysis (n=44,775 in 52 Michigan hospitals) noted anticoagulant (AC) use among low-risk patients (18 584 [57.1%]) was most important contributor to excess use of VTE prophylaxis. Excess use of mechanical VTE prophylaxis was common among both low-and high risk patients.

Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Frail Patients With Nonvalvular Atrial Fibrillation

Journal of the American Heart Association

At 2 yrs, database study (n=19077) found no difference in stroke or systemic embolism (SE) with apixaban or dabigatran (HR=0.78 % 0.94) or major bleeding (0.72 & 0.87) vs warfarin. Rivaroxaban reduced stroke or SE (0.68) without altering major bleeding risk (1.07) vs warfarin.

Revised SPC: Brilique (ticagrelor) – all formulations

electronic Medicines compendium

SPC now states that delayed and decreased exposure to oral P2Y12 inhibitors, including ticagrelor (TG) and active metabolite, has been observed in patients with ACS on morphine (35% reduction in TG exposure). May apply to other opioids; clinical relevance unknown.

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