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

Risk of venous thromboembolism in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a general population-based cohort study

European Heart Journal

This analysis of UK data reports that all three diseases were associated with an increased risk of venous thromboembolism, highest for rheumatoid arthritis (HR 1.29; 95% CI 1.18–1.39 for no DMARD and 1.35, 95% CI 1.27–1.44 for DMARD). An interaction with DMARDs was significant.

 

Treatment of Patients With Atrial Fibrillation and Heart Failure With Reduced Ejection Fraction

Circulation

This review discusses the available data for the treatment of AF in patients who have heart failure with reduced ejection fraction, looks at areas where more investigation is necessary, and presents suggestions for individualised treatment strategies for specific patient groups.

 

Late thrombotic events after bioresorbable scaffold implantation: a systematic review and meta-analysis of randomized clinical trials

European Heart Journal

Review of 5 RCTs (n=1,730) found that patients treated with bioresorbable vascular scaffolds had a higher risk of device thrombisis vs those treated with everolimus eluting stents (OR 2.93, 95% CI 1.37-6.26). There was no statistical difference in risk of target lesion failure.

 

NIHR Signal: Thrombolysis may reduce complications of deep vein thrombosis

National Institute for Health Research Signal

Expert commentary is provided for a systematic review which found that thrombolysis reduced the risk of post-thrombotic syndrome. This benefit however would come at the cost of and increased risk of bleeding. The role of thrombolysis in deep vein thrombosis requires clarification.

 

Anticoagulation reversal for supratherapeutic International Normalized Ratio: A teachable moment

JAMA Internal Medicine

This article describes a case report of a woman in her 80s who underwent anticoagulation reversal, and highlights that fresh frozen plasma transfusions in certain patients with non-urgent conditions can lead to transfusion-associated circulatory overload.

 

Potent P2Y12 Inhibitors in Men Versus Women A Collaborative Meta-Analysis of Randomized Trials

Journal of the American College of Cardiology

Meta-analysis of 7 studies (n=87,840) found no significant difference in efficacy (reduction in risk of major cardiovascular adverse events, myocardial infarction, and stent thrombosis) or safety (major bleeding) for the use of P2Y12 inhibitors in men and women.

 

Effectiveness and safety of rivaroxaban and warfarin in patients with unprovoked venous thromboembolism: a propensity-matched nationwide cohort study

The Lancet Haematology

Danish cohort study (n=4,679 propensity matched patients) found lower rates of recurrent VTE at 6 months for rivaroxaban compared to warfarin (9.9 incidents per 100 person-years vs 13.1 HR 0.74, 95%CI 0.56-0.96). Bleeding rates were similar.

 

Perioperative clopidogrel is associated with increased bleeding and blood transfusion at the time of lower extremity bypass

Journal of Vascular Surgery

Study (n=9179) found perioperative clopidogrel (vs. non use) in lower extremity bypass surgery is linked to increased blood loss (21% vs 12%; p<0.001) and blood transfusion (38% vs 24%; p<0.001), with associated clinical sequelae of increased cardiac and pulmonary 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

Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease

Journal of the American College of Cardiology

Meta-analysis of 4 RCTs noted that in this population without moderate/severe mitral stenosis/mechanical heart valves, NOACs seem attractive alternatives to vitamin K antagonists because coexistence of valvular heart disease does not affect overall relative efficacy/safety.

 

Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes

Heart

Paper reports that long-term bleeding risk during dual antiplatelet therapy (DAPT) for patients with ACS can be reliably predicted with selected baseline characteristics using TRILOGY ACS bleeding risk models thus informing risk–benefit considerations regarding DAPT duration.

 

Stability of repackaged dabigatran etexilate capsules in dose administration aids

European Journal of Hospital Pharmacy

Study reports storage of capsules at ambient conditions for 14 and 28 days resulted in % drug remaining of 92.5% and 71.6%, respectively. In contrast, repackaged capsules stored in fridge for 28 days had drug content of 98.2% and dissolution was not significantly affected.

 

 

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

Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies

European Heart Journal

Data from observational cohort studies suggest beneficial effect of statin on venous thromboembolism recurrence. In pooled analysis of 7 trials, relative risk (RR) was 0.73 (0.68–0.79) vs. no use. RRs for recurrent PE and DVT were 0.75(0.58–0.96) and 0.66 (0.60–0.71) respectively.

 

FDA fast track designation granted for recombinant ADAMTS13 for treatment of hereditary thrombotic thrombocytopenic purpura

Biospace Inc.

Recombinant ADAMTS13 is intended for treatment of acute episodes of hereditary thrombotic thrombocytopenic purpura in patients with a constitutional deficiency of the von Willebrand factor-cleaving protease ADAMTS13. Shire is initiating open-label, 2-period crossover RCT.

 

Should we screen extensively for cancer after unprovoked venous thrombosis?

British Medical Journal

Prevalence of occult cancer in patients with 1st unprovoked venous thromboembolism seems to be lower (~4%) than previously reported (10%). Review notes high quality data from recently completed trials suggest no additional value for extensive screening strategies.

 

Risk of myocardial infarction in patients with atrial fibrillation using vitamin K antagonists, aspirin or direct acting oral anticoagulants

British Journal of Clinical Pharmacology

Real-life cohort study (n=30146) suggests risk of acute myocardial infarction was doubled with direct oral anticoagulants or aspirin vs. vitamin k antagonists (HR 2.11; 95% CI 1.08 – 4.12 and 1.91; 1.45-2.51, respectively). Further research from is required.

 

Two Paradigms for Endovascular Thrombectomy After Intravenous Thrombolysis for Acute Ischemic Stroke

JAMA Neurology

French study of 159 patients ultimately treated by mechanical thrombectomy, of which 100 received IV thrombolysis before transport to a more fully equipped hospital, and 59 did not, found no difference in functional independence at 3 months after stroke between the 2 groups.

 

Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

New England Journal of Medicine

RCT of 3365 patients randomised after 6-12months anticoagulant therapy found symptomatic recurrent fatal/nonfatal venous thromboembolism occurred in 1.5% patients given 20 mg and 1.2% given 10 mg rivaroxaban, vs. 4.4% given aspirin (p<0.001 vs. aspirin for both).

 

Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study

British Medical Journal

This validation study (n= 2785) of the HERDOO2 clinical assessment tool found that women with 0 or 1 of the 4 criteria have a low risk of recurrent venous thromboembolism and can safely discontinue anticoagulants after completing short term treatment.

 

Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation

New England Journal of Medicine

The RE-CIRCUIT trial (n= 704) found that the incidence of major bleeding events after ablation was lower with dabigatran versus warfarin in patients with atrial fibrillation (1.6% vs 6.9%; absolute risk difference, −5.3%; 95% CI, −8.4 to −2.2; P<0.001).

 

Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial

The Lancet

RCT (n= 3,037) found that low-dose rivaroxaban with a P2Y12 inhibitor (clopidogrel or ticagrelor) had a similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes (5% both groups).

 

Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study

The Lancet

Registry data analysis found that leaflet thrombosis was less frequently observed in patients using warfarin or novel oral anticoagulants (eight [4%] of 224) than in those using dual antiplatelet or monoantiplatelet therapy (98 [15%] of 666; p<0•0001).

 

 

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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