Comparative table of low molecular weight heparins

Specialist Pharmacy Service

In light of current shortage of enoxaparin injection (all strengths), this table of the licensed low molecular weight heparins has been drawn up to compare/contrast key prescribing parameters.

 

Coagulopathy and haemorrhagic progression in traumatic brain injury: advances in mechanisms, diagnosis, and management

The Lancet Neurology

This Series paper explores current understanding of clinical course and underlying mechanisms of coagulopathy in traumatic brain injury. Management strategies are reviewed, including traditional use of blood products and more novel approaches, as well as thrombosis prophylaxis.

 

Idarucizumab for Dabigatran Reversal — Full Cohort Analysis

New England Journal of Medicine

Final analysis from RE-VERSE AD (n=510) reported that the primary endpoint, reversal of the anticoagulant effect of dabigatran within four hours as measured by diluted thrombin time and ecarin clotting time, was observed in 100% of patients (95% CI, 100-100).

 

Revised SPC: Xarelto (rivaroxaban) film coated tablets (all strengths)

electronic Medicines Compendium

Serious skin reactions, including Stevens-Johnson syndrome/Toxic Epidermal Necrolysis, have been reported. The highest risk appears to be early in the course of therapy. Treatment should be discontinued at the first appearance of a severe skin rash.

 

Initial anticoagulation in patients with pulmonary embolism: thrombolysis, unfractionated heparin, LMWH, fondaparinux, or DOACs?

British Journal of Clinical Pharmacology

This article gives an overview of the biophysical, pharmacokinetic and pharmacodynamic properties of anticoagulants currently available for the initial management of PE including low molecular weight heparins and direct oral anticoagulants.

 

 

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

Low-Molecular-Weight Heparin and the Relative Risk of Surgical Site Bleeding Complications: Results of a Systematic Review and Meta-Analysis of Randomized Controlled Trials of Venous Thromboprophylaxis in Patients After Total Joint Arthroplasty

Journal of Arthroplasty

Review of 45 RCTs (n= 56,730) found low-molecular-weight heparin had increased relative risk (RR) of surgical site bleeding vs. control (2.32; 95% CI, 1.40-3.85), warfarin (1.54; 1.23-1.94), and dabigatran (4.38; 1.53-12.57). There was trend towards increased risk vs. apixaban.

 

U.S. FDA grants priority review of rivaroxaban supplemental new drug application for 10 mg dose to reduce risk of recurrent venous thromboembolism (VTE)

Biospace Inc.

Application is for use of 10 mg once-daily dose to reduce risk of VTE after ≥6 months of standard anticoagulation and is based on data from EINSTEIN CHOICE study which found 2 doses of rivaroxaban (10 mg and 20 mg) to be superior to aspirin in reducing risk of recurrent VTE.

 

Risk for Major Bleeding in Patients Receiving Ticagrelor Compared with Aspirin After TIA or Acute Ischemic Stroke in the SOCRATES Study

Circulation

Review of the SOCRATES study found that bleeds occurred in 0.5% of patients on ticagrelor and 0.6% of patients on aspirin (HR 0.83 95% CI 0.52 to 1.34). Intracranial haemorrhage was reported in 0.2% of patients on ticagrelor and 0.3% on aspirin.

 

Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia: A Systematic Review

Annals of Internal Medicine

No RCTs were identified. Review of 24 observational studies (n=6153) noted no extractable data on anticoagulants, lack of uniform bleeding definitions, and systematic reporting of outcomes, thus risk–benefit ratio of antiplatelets in essential thrombocythemia is highly uncertain.

 

Conference report- Assessing the risk-benefit of anticoagulants in elderly patients with cancer-associated venous thromboembolism: a population based study

Biospace Inc.

Population-based retrospective cohort study found use of anticoagulants in patients ≥65 years with cancer-related thrombosis results in higher mortality if they develop major bleeding (MB) compared to venous thromboembolic event [VTE] (7-day mortality rate:0.5% VTE vs. 11% MB).

 

Conference report: Emicizumab showed positive results in phase III studies (HAVEN 1 and HAVEN 2) in haemophilia A with inhibitors

Biospace Inc.

HAVEN 1 showed statistically significant reduction in bleed rate of 87% (risk rate 0.13, p<0.0001) with emicizumab prophylaxis vs. on-demand treatment with bypassing agents. HAVEN 2 study noted after 12 weeks, 1 of 19 children on emicizumab reported a treated bleed.

 

FDA approves betrixiban (BevyxXa) for preventing blood clots in hospitalised patients

PharmaTimes

The US approval was based on findings of the APEX Study (n=7513), which found that betrixiban reduced incidence of DVT and PE vs enoxaparin (4.4% vs 6.0%) with no significant increase in major bleeding (0.67% vs. 0.57%).

 

 

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

Use of the Dual-Antiplatelet Therapy Score to Guide Treatment Duration After Percutaneous Coronary Intervention

Annals of Internal Medicine

Retrospective analysis of 1970 patients undergoing PCI reports prolonged dual-antiplatelet therapy (DAPT) resulted in harm in patients with low DAPT scores but reduced risk for ischaemic events in patients with high scores receiving paclitaxel-eluting stents.

 

Antithrombotic treatment after stroke due to intracerebral haemorrhage

Cochrane Database of Systematic Reviews

This review of two RCTs (n=121) concludes there is insufficient evidence to support or discourage the use of antithrombotic treatment after ICH. RCTs comparing starting vs avoiding antiplatelets /anticoagulants after ICH appear justified and are needed in clinical practice.

 

The role of contraindications in prescribing anticoagulants to patients with atrial fibrillation: a cross-sectional analysis of primary care data in the UK

British Journal of General Practice

Analysis (2004-2012) found presence/absence of recorded contraindications (CIs) has little influence on decision to prescribe anticoagulants (ACs) for prevention of stroke in AF patients. Nationally, 38,000 with AF and CIs were treated with ACs, which has safety implications.

 

It Is Time to End the Dualistic Short Versus Long Duration of Dual Antiplatelet Therapy Debates

Circulation

Viewpoint suggests it is time to end academic debate and begin clinical discussion, with a shift in focus away from dualistic short versus long duration thinking and towards discussions on which patients are best treated with short, standard or prolonged dual antiplatelet therapy.

 

Antiplatelet Therapy in Patients With Coronary Stents Undergoing Elective Noncardiac Surgery: Continue, Stop, or Something in Between?

Journal of the American Medical Association

Viewpoint notes that based on available, evidence, there is no clear link between antiplatelet strategy and rates of perioperative major adverse CV events and bleeding, even though physiological reasons would suggest that antiplatelet agents should be a factor in the risk of both.

 

Review: Indications and appropriate selection of novel oral anticoagulants in patients with atrial fibrillation

Heart

This review notes that in the absence of RCT evidence, patient-specific factors such as dosing preference (daily vs twice a day), renal function, liver function, gastrointestinal bleeding risks and drug–drug interactions can help guide treatment choice.

 

 

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

Management of superficial venous thrombosis of the leg

Drug and Therapeutics Bulletin

Review notes lack of consensus on best treatment but oral NSAIDs and compression stockings are used to provide symptomatic relief for pain and swelling. Guidelines suggest that fondaparinux or a low molecular weight heparin are options for some high risk patients.

 

Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial

The Lancet Haematology

RCT (n=100, Austria) was terminated early for futility and safety reasons because compared to patients on coagulation factor concentrates, a higher proportion of patients receiving fresh frozen plasma required rescue therapy (52 vs. 4%) and massive transfusion (30 vs. 12%).

 

Reversal strategies for non-vitamin K antagonist oral anticoagulants: a critical appraisal of available evidence and recommendations for clinical management—a joint position paper of the European Society of Cardiology Working Group

European Heart Journal

Paper notes that while available clinical data for specific antidotes of NOACs are limited, it is very likely these agents will successfully reverse.

 

Thrombophilia Testing in Provoked Venous Thromboembolism: A Teachable Moment

JAMA Internal Medicine

This Teachable Moment looks at the value of testing for inherited thrombophilia in patients with provoked venous thrombophilia.

 

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 treatment of paroxysmal atrial fibrillation in UK primary care

Heart

The proportion of patients with a CHADS2 score of ≥1 prescribed anticoagulants increased between 2000 and 2015. Although improved, use in those with paroxysmal AF remains lower in 2015 (56.2% versus 69.4% in patients with persistent/permanent AF, RR 0.76; 95% CI 0.74 to 0.77).

 

Diagnosis and management of deep vein thrombosis in pregnancy

British Medical Journal

The incidence of DVT among pregnant women is around 1.1 per 1000 deliveries. This article provides an update on the diagnosis and management of pregnant women with DVT.

 

 

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

Clopidogrel reloading for patients with acute myocardial infarction already on clopidogrel therapy

European Heart Journal

This analysis of patients admitted to hospital with myocardial infarction who were on clopidogrel pre-admission (n=12,366 STEMI and 39,158 NSTEMI) found that reloading (75.8% STEMI and 25.9% NSTEMI) was not associated with increased risk of major bleeding or mortality.

 

Specific antidotes for bleeding associated with direct oral anticoagulants

British Medical Journal

This BMJ 'Practice' article discusses strategies to reverse anticoagulant activity of direct oral anticoagulants (DOACs), focusing on newer specific antidotes (idarucizumab [the only one currently licensed]; andexanet alfa, and ciraparantag).

 

 

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

Unfractionated heparin versus low molecular weight heparins for avoiding heparin‐induced thrombocytopenia in postoperative patients

Cochrane Database of Systematic Reviews

Updated review of 3RCTs (n=1398) demonstrated low-quality evidence of a lower incidence of heparin-induced thrombocytopenia (HIT), and HIT complicated by venous thromboembolism, in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH.

 

Influence of Direct Oral Anticoagulants on Rates of Oral Anticoagulation for Atrial Fibrillation

Journal of the American College of Cardiology

Study (n=655,000; CHA2DS2-VASc >1) in US found introduction of DOACs into routine practice linked to improved rates of overall oral anticoagulant use (from 52.4% to 60.7%; p<0.01; warfarin use decreased 52.4% to 34.8%; DOAC use increased 0% to 25.8%) but significant gaps remain.

 

Anticoagulation in patients with isolated distal deep vein thrombosis: a meta-analysis

Journal of Thrombosis and Haemastasis

Review of 20 studies (n= 2,936) found that anticoagulation (therapeutic or prophylactic) reduced to the risk of VTE vs no anticoagulation (OR 0.5, 95% CI 0.31-0.79). There was no significant difference in major bleeding risk (OR 0.64, 0.15-2.73).

 

FDA grant fast track designation for SB-525 gene therapy for haemophillia

PharmaTimes

SB-525 uses a recombinant adeno-associated virus (rAAV) to deliver a human Factor VIII cDNA construct. This treatment also has orphan designation in the US. EU development plans are unknown.

 

Revised SPC: Pradaxa (dabigatran etexilate) hard capsules – all strengths

electronic Medicines Compendium

The colour of Pradaxa caps have been changed according to dosage strength, as part of the worldwide harmonisation process.

 

Risk Minimisation materials for Pradaxa capsules (dabigatran etexilate): Prescriber guides for various indications and Patient Alert Card

electronic Medicines Compendium

The Prescriber guide for primary prevention of venous thromboembolic events following elective hip or knee replacement surgery provides recommendations for orthopaedic use with the aim of minimising risk of bleeding, and providing guidance on how to manage that risk.

 

Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study

European Heart Journal

RCT (n=645) reports switching dual antiplatelet therapy (DAPT) from aspirin + newer P2Y12 blocker to clopidogrel after 1 month results in occurrence of primary endpoint (composite CV death, urgent revascularisation, stroke and bleeding) of 26.3% vs 13.4% respectively (P < 0.01).

 

Educational Risk Minimisation Materials for Clexane (enoxaparin sodium)

Sanofi UK

Dear Healthcare Professional" letter notes that enoxaparin is expressed both in international units (IU) of anti-Xa activity and in milligrams (mg); and that its use in severe renal impairment is not recommended. There is also further clarification on dose regimens for DVT/PE.

 

 

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

Integrated care in atrial fibrillation: a systematic review and meta-analysis

Heart

The results of this analysis suggest that use of an integrated model of care delivery in AF, with multidisciplinary team and community supports to ensure patient involvement in their management and decisions involving their care, is associated with enhanced patient outcomes.

 

Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data

British Medical Journal

Cohort review (446,763 individuals) found an increased risk for myocardial infarction with the use of several NSAIDs for 1-7 days; ibuprofen, HR 1.48 (95% CI 1.00 to 2.26), diclofenac 1.50 (1.06-2.04), naproxen 1.53 (1.07-2.33) and rofecoxib, 1.58 (1.07-2.17).

 

Pharmacovigilance Risk Assessment Committee (PRAC) review of factor VIII medicines

European Medicines Agency

This review has concluded that there is no clear and consistent evidence of difference in the incidence of inhibitor development between the plasma-derived and recombinant DNA technology-derived classes of factor VIII medicines.

 

 

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

Trends in the prescription of novel oral anticoagulants in UK primary care

British Journal of Clinical Pharmacology

Data from the UK CPR Datalink (between 2009-2015) shows the overall rate of oral anticoagulant initiation increased by 58% over the study period despite the rate of new VKA use decreasing by 31%. The rate of initiation of NOAC increased, with a 17-fold increase from 2012 to 2015.

 

Gastrointestinal Safety of Direct Oral Anticoagulants: A Large Population-Based Study

Gastroenterology

This study (n=43,303) found GI bleeding occurred more frequently with rivaroxaban than dabigatran (HR, 1.20; 95% CI, 1.00-1.45), whereas apixaban was associated with lower bleeding risk than dabigatran (0.39; 0.27-0.58; P <0.001) or rivaroxaban (0.33; 0.22-0.49; P < 0.001).

 

 

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 the Relative Efficacy and Safety of Oral P2Y12 Inhibitors in Patients With Acute Coronary Syndrome

American Journal of Cardiology

Meta-analysis of 9 RCTs (n= 106,288) suggests that overall, ticagrelor may have the best net efficacy and safety profile among currently approved oral P2Y12 inhibitors for the treatment of acute coronary syndrome.

 

 

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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