Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

Cochrane Database of Systematic Reviews

Review of 7 RCTs (n=1728) concludes prolonged thromboprophylaxis (≥14 days) with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications after major abdominal or pelvic surgery.

Major Bleeding Rates in Atrial Fibrillation Patients on Single, Dual, or Triple Antithrombotic Therapy: Results from a Nationwide Danish Cohort Study

Circulation

Study (n=272,315) found triple therapy linked to high rates of major bleeding vs. dual or monotherapy. Very high major bleeding rates occurred among patients on triple therapy aged > 90 years or with CHA2DS2-VASc > 6 or with a history of major bleeding.

Association of Oral Anticoagulants and Proton Pump Inhibitor Co-therapy With Hospitalization for Upper Gastrointestinal Tract Bleeding

Journal of the American Medical Association

Retrospective study found during 754,389 person-years of anticoagulation with apixaban, dabigatran, rivaroxaban [RV], and warfarin, risk of hospitalisation for upper GI bleeding was highest for RV. PPI cotherapy (264,447 person-years) was linked to lower overall GI bleeding risk.

Apixaban to Prevent Venous Thromboembolism in Patients with Cancer

New England Journal of Medicine

RCT (n=574) found apixaban (2.5mg BD) resulted in lower rate of venous thromboembolism vs. placebo in intermediate/high-risk ambulatory patients with cancer starting chemo (12 [4.2%] vs. 28 [10.2%]; HR 0.41; 95% CI, 0.26-0.65; p<0.001) but higher rates of major bleeding episodes.

Conference report: positive results for emicizumab for paediatric haemophilia A

Biospace Inc.

Primary analysis of the HAVEN 2 study (n=85) has found that once-weekly emicizumab dosing showed a 99% reduction in treated bleeds compared to prior treatment with bypassing agents.

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

Early Risks of Death, Stroke/Systemic Embolism and Major Bleeding in Patients with Newly Diagnosed Atrial Fibrillation: Results from the GARFIELD-AF Registry

Circulation

Registry study (n=52,014) found an elevated mortality rate in the first month after diagnosis vs the first year (6.8 vs 4.3 100 person years for first month and first year respectively). The elevated 1-month mortality rate was mostly attributable to cardiovascular mortality.

Subcutaneous treprostinil for the treatment of severe non-operable chronic thromboembolic pulmonary hypertension (CTREPH): a double-blind, phase 3, randomised controlled trial

The Lancet Respiratory Medicine

RCT (N=105) reported an improvement from baseline in mean 6-min walk distance in the treprostinil high and low dose groups (44·98 m and 4·29 m; p=0·0016). Treprostinil is an investigational prostacyclin analogue that has received orphan drug status in the EU.

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

Efficacy and Safety of Drug-Eluting Stents Optimized for Biocompatibility vs Bare-Metal Stents With a Single Month of Dual Antiplatelet Therapy: A Meta-analysis

JAMA Cardiology

This review of 3 RCTs (n=3943) comparing bare-metal stents (BMSs) to drug-eluting stents (DESs) with shortened duration of dual antiplatelet therapy (one month only) found DES were associated with lower risk of major adverse cardiac events and other adverse outcomes.

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

The role of plasminogen activators in stroke treatment: fibrinolysis and beyond

The Lancet Neurology

This review describes the pathophysiological effects of plasminogen activators and how, in the future, their non-fibrinolytic functions could be used for the treatment of patients with acute ischaemic and haemorrhagic stroke.

Practice guide to dosing of direct acting oral anticoagulants in patients with renal impairment

Specialist Pharmacy Service

This paper, focusing on use of DOACs in patients with atrial fibrillation, discusses the debate regarding the dosing of DOACs in patients with renal impairment and offers some practical advice on selecting the dose in the clinical setting.

Management of life threatening bleeds from arteriovenous fistulae and grafts

NHS Improvement

Alert signposts providers to resources produced jointly by British Renal Society and Vascular Access Society of Britain and Ireland to help staff, carers and patients recognise warning signs. Providers are asked to ensure local guidance incorporates advice in these resources.

Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke

Cochrane Database of Systematic Reviews

Review (4 trials, n=450) found no RCT evidence that percutaneous vascular interventions are superior to intravenous thrombolytic treatment with respect to functional outcome. Quality of evidence was low (outcome assessment was blinded but not treating physician/participants).

Performance of the ABC Scores for Assessing the Risk of Stroke or Systemic Embolism and Bleeding in Patients with Atrial Fibrillation in ENGAGE AF-TIMI 48

Circulation

Paper reports that ABC-stroke and ABC-bleeding risk scores which comprise clinical variables and CV biomarkers to estimate risk of stroke/systemic embolic events and bleeding, respectively, were well-calibrated and outperformed the CHA2DS2-VASc and HAS-BLED scores, respectively.

Self‐poisoning with 60 tablets of Apixaban, a pharmacokinetics case report

British Journal of Clinical Pharmacology
Apixaban was eliminated following first order elimination with a calculated half‐life of 10.8 h. Anti‐Xa activity seems to be linearly related to concentration up to 4000 μg/ l. This report suggests use of activated charcoal should be effective up to 17 h after a massive intake.

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

Barriers to a software reminder system for risk assessment of stroke in atrial fibrillation: a process evaluation of a cluster randomised trial in general practice

British Journal of General Practice

An evaluation of 23 practices found that an automated risk assessment for stroke in AF and prompting during consultations are feasible and generally acceptable, but did not overcome concerns about frailty and risk of haemorrhage as barriers to anticoagulant uptake.

Revised SPCs: Plavix (clopidogrel) 75 and 300mg tablets

electronic Medicines compendium

Insulin autoimmune syndrome has been added to SPCs as an adverse effect (unknown frequency). This can lead to severe hypoglycaemia, particularly in patients with HLA DRA4 subtype (more frequent in the Japanese population).

Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation

The Lancet Neurology

This Rapid Review summarises and critically reviews current guidelines and new published data, and gives an overview of ongoing investigator-initiated randomised controlled trials of oral anticoagulation timing after ischaemic stroke associated 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:

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

Impact of anticoagulant choice on hospitalized bleeding risk when treating cancer-associated venous thromboembolism

Journal of Thrombosis and Haemastasis

This US retrospective study (26,894 people with cancer-associated venous thrombosis), found that the bleeding risk with DOACs was similar to warfarin and low molecular weight heparin. There was however heterogeneity in bleeding risk with DOACs by cancer type.

Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation: A Systematic Review

Annals of Internal Medicine

Review of 220 articles aimed to compare the effectiveness of medical and procedural therapies in preventing thromboembolic events and bleeding complications in adults with non-valvular AF. It found DOACs are at least as effective and safe as warfarin for patients.

Idarucizumab for Dabigatran Reversal in the Management of Patients with Major Gastrointestinal Bleeding

Circulation

In RE-VERSE AD trial, idarucizumab showed rapid/complete reversal of dabigatran activity in nearly all patients with GI bleeding; complete reversal in 118 of 121 (97.5%) with elevated diluted thrombin time at presentation and 95 of 131 (72.5%) with elevated ecarin clotting time.

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome

Blood

Trial (n=120) was terminated early due to an excess of events in the rivaroxaban group compared to warfarin (7 thromboembolic events; 4 ischemic stroke and 3 myocardial infarction vs. 0 events, respectively). Major bleeding occurred in 4 vs. 2 patients, 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:

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

Extended treatment of venous thromboembolism: a systematic review and network meta-analysis

Heart

Review of 16 studies (n=22,000) found that, for extended treatment, vitamin K antagonists (VKAs) and direct oral anticoagulants reduced the risk of recurrent venous thromboembolisms vs aspirin. The risk of bleeding was higher with high and standard intensity VKAs however.

NIHR Signal: The blood-thinner apixaban is less likely to cause major bleeding than warfarin

National Institute for Health Research Signal

Expert commentary is provided for a cohort study which found a lower rate of major bleeding with apixaban vs warfarin (HR 0.66, 95%CI 0.54- 0.79). Residual confounding is likely however, and these data should only be considered supportive of randomised trials, not replacing them.

Venous Thromboembolism: Advances in Diagnosis and Treatment

Journal of the American Medical Association

Amongst other points, this review of 32 studies from the US perspective notes that the introduction of direct oral anticoagulants has allowed for a simplified treatment and has made extended secondary prevention more acceptable.

European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism

European Heart Journal

A patent foramen ovale is implicated in pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This paper reviews available trial evidence and defines principles needed to guide decision making.

Association of Genetic Variants With Warfarin-Associated Bleeding Among Patients of African Descent

Journal of the American Medical Association

This case-control study (n=215) in patients of African descent found that 4 single nucleotide polymorphisms on chromosome 6 were associated with an increased risk of major bleeding at INR<4. Authors highlight that validations in an independent prospective cohort is required.

Spontaneous splenic rupture due to rivaroxaban

Drug and Therapeutics Bulletin

This summary describes the fifth case report of of spontaneous splenic rupture of a patient treated with rivaroxaban and highlights that this has also been reported with apixaban and dabigatran. It suggests key learning points, including checking for drug interactions.

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

Individually shortened duration versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome: a cost-effectiveness analysis

The Lancet Haematology

Dutch RCT (n=865) found that, using the UK tariff for EQ-5D for ascertaining Quality Adjusted Life Years, an individualised strategy was more effective in clinical outcomes and less costly than standard 2 years of elastic stocking compression therapy.

P2Y12-ADP Receptor Blockade in Chronic Kidney Disease Patients With Acute Coronary Syndromes: Review of the Current Evidence

Circulation

This review summarises the mechanisms involved in the high ischaemic and bleeding risk of patients with chronic kidney disease CKD and the risk–benefit ratio of potent antiplatelet drugs during acute coronary syndrome.

Rivaroxaban (Xarelto▼) after transcatheter aortic valve replacement:increase in all-cause mortality, thromboembolic and bleeding events in a clinical trial

Medicines and Healthcare products Regulatory Agency

MHRA advises that rivaroxaban treatment in patients who undergo transcatheter aortic valve replacement should be stopped and switched to standard of care. It notes rivaroxaban is not licensed for thromboprophylaxis in patients with prosthetic heart valves, and should not be used.

Atrial fibrillation, antithrombotic treatment, and cognitive aging: A population-based study

Neurology

Swedish cohort study (n=2685) found AF linked to faster global cognitive decline and an increased risk of all cause dementia in older people (HR 1.40, 95% CI, 1.11–1.77). Use of anticoagulant drugs (but not antiplatelets) may reduce dementia risk in this group (0.40; 0.18–0.92).

Surgery versus thrombolysis for initial management of acute limb ischaemia

Cochrane Database of Systematic Reviews

This updated review (5 RCTs; nil new) concludes there is currently no evidence in favour of either initial thrombolysis or initial surgery as the preferred option in terms of limb salvage, amputation, or death; thrombolysis may be associated with higher risk 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:

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

Prevalence, Safety, and Effectiveness of Oral Anticoagulant Use in People with and without Dementia or Cognitive Impairment: A Systematic Review and Meta-Analysis

Journal of Alzheimer's Disease

Review of 27 trials found fewer people with dementia (DM) received oral anticoagulation (AC) vs. people without DM (32 v. 48%) but there was no difference in composite of embolic events/MI/all-cause death. People with DM had higher bleeding risk and poorer AC control on warfarin.

Antiplatelet and anticoagulant agents for primary prevention of thrombosis in individuals with antiphospholipid antibodies

Cochrane Database of Systematic Reviews

Review of 9 studies (n=1,044) found insufficient evidence to demonstrate benefit or harm of using anticoagulants with or without aspirin versus aspirin alone in people with antiphospholipid antibodies and a history of recurrent pregnancy loss and with no such history.

NIHR Signal: Two antiplatelet drugs may prevent further strokes but increase major bleeds

National Institute for Health Research Signal

Expert commentary is provided for an RCT which found that clopidogrel plus aspirin resulted in fewer ischaemic events, but more major bleeds vs aspirin. There may be a place for dual anti-platelets, but UK practice is clopidogrel monotherapy, and the comparator here was aspirin.

Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial

British Medical Journal

RCT (n=870) found dual antiplatelet therapy (DAPT) to 6 months was non-inferior to DAPT for 12 months in patients with event-free STEMI at 6 months after primary PCI with second generation drug-eluting stents (HR 0.73, 95% CI, 0.41-1.27, p=0.26, and p=0.004 for non-inferiority).

Periprocedural Outcomes of Direct Oral Anticoagulants Versus Warfarin in Nonvalvular Atrial Fibrillation: Meta-Analysis of Phase III Trials

Circulation

Analysis of 4 substudies found no difference in stroke/systemic embolism, major bleeding, or death linked to procedures requiring temporary interruption of DOACs /warfarin (WF). For procedures using uninterrupted anticoagulation, DOACs had 38% lower risk of major bleeding vs. WF.

Anticoagulation for perioperative thromboprophylaxis in people with cancer

Cochrane Database of Systematic Reviews

Review (20 RCTs; n=9771) found no difference between perioperative thromboprophylaxis with low molecular weight heparin (LMWH) vs unfractionated heaparin and LMWH vs fondaparinux in their effects on mortality, thromboembolic outcomes, major bleeding, or minor bleeding.

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

The Lancet Haematology

Sub group analysis (n=534) found that rivaroxaban was associated with fewer recurrent stroke events than aspirin (4.8 versus 2.6 events/100 person-years) but this effect was not statistically significant.

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome

Blood

This study comparing rivaroxaban and warfarin (target INR 2.5) in high-risk patients with thrombotic antiphospholipid syndrome was terminated prematurely (120 patients enrolled) due to an excess of events in the rivaroxaban group (19% v 3% with warfarin).

US FDA approves emicizumab (Hemlibra) to prevent or reduce frequency of bleeding episodes in patients with haemophilia A without factor VIII inhibitors

Biospace Inc.

Approval was based on data from the Phase III HAVEN 3 and HAVEN 4 trials, which showed it was associated with clinically meaningful reductions in treated bleeds compared to no prophylaxis. In the EU it is currently approved only for use in patients with factor VIII inhibitors.

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

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