Revised SPC: Dipyridamole 50mg/5ml Oral Suspension

electronic Medicines Compendium

Angina pectoris, post procedural haemorrhage and operative haemorrhage have been added as adverse reactions of dipyridamole.

 

Revised SPC: Nebido (testosterone undecanoate) 1000mg/4ml, solution for injection

electronic Medicines Compendium

Section 4.4 of SPC now includes warning that testosterone should be used with caution in patients with thrombophilia, as there have been post-marketing studies and reports of thrombotic events in these patients during testosterone therapy.

 

Direct-acting antivirals to treat chronic hepatitis C: risk of interaction with vitamin K antagonists and changes in INR

Medicines and Healthcare products Regulatory Agency

It is advised that INR should be monitored closely during treatment of chronic hepatitis C with direct-acting antivirals in patients also receiving vitamin
K antagonists (e.g. warfarin), because of possible changes in liver function during treatment.

 

Incidence of venous thromboembolism in care homes: a prospective cohort study

British Journal of General Practice

During a mean follow-up period of 312 days, this observational cohort study (n=1011) reports an increased incidence of venous thromboembolism in care homes compared to the community setting in people aged over 70 years.

 

Valvular heart disease and pregnancy part II: management of prosthetic valves

Heart

This is a review of pregnancy risks in women with prosthetic heart valves, strategies for anticoagulation in women with mechanical heart valves, and the management 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

Discontinuation of Warfarin Therapy for Patients With Atrial Fibrillation: The Michigan Anticoagulation Quality Improvement Initiative Experience

JAMA Cardiology

Research letter-reports on study (n=734) which showed high rate of discontinuation of warfarin within first year (36.8%), especially among patients undergoing electrical cardioversion or radiofrequency ablation (54.1% vs.29.5% not undergoing these procedures; p<0.001).

 

Antifibrinolytic therapy to reduce haemoptysis from any cause

Cochrane Database of Systematic Reviews

There is insufficient evidence to judge whether antifibrinolytics should be used to treat haemoptysis from any cause, though limited evidence suggests they may reduce the duration of bleeding.

 

Safety profile of the direct oral anticoagulants: an analysis of the WHO database of adverse drug reactions

British Journal of Clinical Pharmacology

This analysis of 32,972 reports of adverse events (from WHO VigiBase database) shows increased risk of gastrointestinal haemorrhage in patients treated with
direct oral anticoagulants vs warfarin (OR 1.6, p≤0.05), and a reduced risk of intracranial haemorrhage (OR 0.31, p≤0.05).

 

Heparin for the treatment of thrombosis in neonates

Cochrane Database of Systematic Reviews

No studies were identified that met the inclusion criteria for this evaluation, and therefore no recommendations can be made for the use of heparin for the
treatment of neonates with thrombosis.

 

A novel risk prediction score in atrial fibrillation for a net clinical outcome from the ENGAGE AF-TIMI 48 randomized clinical trial

European Heart Journal

This paper describes development of a risk score (TIMI-AF) using data from ENGAGE AF-TIMI 48 trial (edoxaban vs. warfarin) to identify vitamin K antagonist
(VKA) naive patients for whom a therapeutic benefit of non-vitamin K antagonist oral anticoagulants over a VKA is predicted.

 

Prospective study of oral anticoagulants and risk of liver injury in patients with atrial fibrillation

Heart

Analysis (n=113,717 with AF, mean age 70, 39% women) found that over median 12 months follow-up, there were 960 hospitalisations with liver injury with rates for following anticoagulants: 9 (warfarin), 4.0 (dabigatran), 6.6 (rivaroxaban) and 5.6 (apixaban), per 1000 person-years.

 

Combined Intravenous Thrombolysis and Thrombectomy vs Thrombectomy Alone for Acute Ischemic Stroke: A Pooled Analysis of the SWIFT and STAR Studies

JAMA Neurology

Analysis (n=291) found that treatment of patients experiencing acute ischaemic stroke due to a large vessel occlusion with intravenous thrombolysis before
mechanical thrombectomy (MT) did not appear to provide a clinical benefit over MT alone.

 

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

The Lancet

RCT (n=500) found in patients with intraventricular haemorrhage and routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes (modified Rankin Scale score ≤3 at 180 days) compared with irrigation with saline, but seems safe.

 

Afstyla (recombinant human coagulation factor VIII, single chain) approved in EU for treatment of haemophilia A

Biospace Inc.

Afstyla, the first and only single-chain product, is approved for treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor
VIII deficiency) in all age groups. It is specifically designed for protection from bleeds with 2 or 3 times weekly dosing.

 

Biologic Licence Application for coagulation factor VIIA recombinant, (Eptacog beta activated) accepted for review by FDA

Biospace Inc.

The pivotal phase 3 trial supporting licence application for this new treatment for patients with haemophilia A and B tested two initial dose regimens in 468
bleeding events occurring in 27 inhibitor patients. Both study arms met the primary end point of haemostatic success.

 

Oral anticoagulation in end-stage renal disease and atrial fibrillation: is it time to just say no to drugs?

Heart

Review notes clinicians who initiate vitamin K antagonists in this group should expect substantial lability in anticoagulant activity and pursue an aggressive monitoring strategy; use of DOACs in moderate renal impairment pose theoretical risks and lack safety data in dialysis.

 

Statins and primary prevention of venous thromboembolism: a systematic review and meta-analysis

The Lancet Haematology

Review of 13 cohort studies and 23 RCTs (total n=3,266,723) found a pooled RR for VTE of 0.75 (95% CI 0.65-0.87) for cohort studies and 0.85 (0.73-0.99) for RCTs for statin vs placebo or no treatment. Rosuvastatin had the lowest risk vs other statins (RR 0.57, 0.42-0.75).

 

 

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

Thrombolysis for acute deep vein thrombosis

Cochrane Database of Systematic Reviews

Evidence suggests that systemic administration and catheter-directed thrombolysis have similar effectiveness. Strict eligibility criteria may be necessary to reduce the risk of bleeding complications, but may limit the applicability of this treatment.

 

Impact of an Interaction Between Clopidogrel and Selective Serotonin Reuptake Inhibitors

American Journal of Cardiology

Findings from large, population-based study in US suggest being treated with CYP2C19-inhibiting SSRI (fluoxetine/fluvoxamine) when initiating clopidogrel
may be linked to increased risk of ischaemic events (HR 1.12; 95% CI, 1.01-1.24) vs. those treated with noninhibiting SSRI.

 

Impact of self-funding on patient experience of oral anticoagulation self-monitoring: a qualitative study

BMJ Open

Analysis of 26 interviews noted variable provision of self-monitoring equipment caused resentment and there were worries about cost of test strips. However,
self-funding did mean that interviewees felt a sense of ownership and were determined to persevere to overcome problems.

 

Revised SPC: Sustanon 250, 250mg/ml solution for injection (testosterone propionate, testosterone phenylpropionate, testosterone isocaproate, testosterone decanoate)

electronic Medicines Compendium

Section 4.4 now advises that testosterone should be used with caution in patients with thrombophilia, as there have been post-marketing studies and reports of thrombotic events in these patients during testosterone therapy.

 

US FDA and European Medicines Agency (EMA) accept for a review, a marketing authorisation application for betrixaban

Biospace Inc.

Betrixaban is an oral, once-daily Factor Xa inhibitor anticoagulant, for extended-duration prophylaxis of venous thromboembolism (VTE) in acute
medically ill patients with risk factors for VTE. The application is based on data from the phase III APEX study.

 

 

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

Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal

Thrombosis and Haemostasis

Review found prothrombin complex concentrate (PCC) normalises INR more often and faster than fresh frozen plasma in warfarin-treated patients with major
bleeding/need for urgent surgery/ invasive procedure. PCCs were also less likely to cause volume overload or heart failure.

 

NIHR Signal: Long-haul flyers could reduce risk of leg blood clots with compression stockings

National Institute for Health Research Signal

This is an expert commentary of a Cochrane review which found that airline passengers could reduce their risk of getting a deep vein thrombosis by wearing
compression stockings, even if they are at low risk.

 

NIHR Signal: People prefer shorter compression stockings to prevent blood clots

National Institute for Health Research Signal

This is an expert commentary of a systematic review which found people having surgery prefer wearing knee length to thigh length compression stockings to prevent deep vein thrombosis, and are more likely to wear knee length stockings correctly and for the recommended time.

 

 

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

Patients' perceptions and experiences of the prevention of hospital-acquired thrombosis: a qualitative study

BMJ Open

Semi-structured interviews with 31 patients requiring venous thromboembolism (VTE) prophylaxis following recent hospital admission in UK found good adherence to heparin and poor adherence to elastic compression stockings, as well as limited knowledge of signs and symptoms of VTE.

 

Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling of an observational cohort

BMJ Open

Analysis of data on 3566 adults from 33 A+Es found CT scanning for all anticoagulated patients with head injury is not cost-effective (£94,895/QALY gained) vs. selective scanning based on guidelines recommending scanning only for those with evidence of traumatic brain injury.

 

Thrombus Aspiration in ST Elevation Myocardial Infarction: An Individual Patient Meta-analysis

Circulation

Review of 3 RCTs (n=19,047) found no difference in CV death at 30 days for thrombus aspiration plus PCI vs PCI alone, however in those with high thrombus burden (TIMI thrombus grade ≥3) thrombus aspiration was associated with less CV death (2.5% vs 3.1%, HR 0.80; 95%CI 0.65-0.98).

 

 

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

 

Pentasaccharides for the prevention of venous thromboembolism

Cochrane Database of Systematic Reviews

Review (n=21004) found moderate to high quality evidence that fondaparinux is effective for short term prevention of VTE vs. placebo. Low to moderate quality evidence shows that fondaparinux is effective for short-term prevention of VTE vs. low molecular weight heparin.

 

A Critical Appraisal of Aspirin in Secondary Prevention: Is Less More?

Circulation

This article critically reviews the available evidence for aspirin use after ACS and PCI and discusses the scientific rational for ongoing studies testing the risks and benefits of omission or early discontinuation of aspirin in favor of P2Y12 inhibitor monotherapy.

 

Development and validation of risk prediction model for venous thromboembolism in postpartum women: multinational cohort study

British Medical Journal

This cohort study based on 433 353 deliveries in England and 662 387 in Sweden has been used to develop a new prediction model that quantifies absolute risk of postpartum VTE based on clinical variables in order to serve as the basis for decisions on obstetric thromboprophylaxis.

 

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism

Cochrane Database of Systematic Reviews

Moderate quality evidence suggests that combining IPC and pharmacological prophylaxis, compared with either alone, decreases the incidence of DVT when compared to compression, and incidence of PE when compared to anticoagulation.

 

Thromboprophylaxis after Knee Arthroscopy and Lower-Leg Casting

New England Journal of Medicine

Two open label RCTs (n=1,543; n=1,519) found no significant difference in the rate of VTE for 8 days prophylactic LMWH vs no thromboprophylaxis post arthroscopy or prophylactic LMWH or no thromboprophylaxis after cast treatment.

 

 

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

Compression stockings for preventing deep vein thrombosis in airline passengers

Cochrane Database of Systematic Reviews

Review found high-quality evidence that airline passengers can expect a substantial reduction in the incidence of symptomless DVT and low-quality evidence that leg oedema is reduced if passengers wear compression stockings.

 

Antiplatelet versus anticoagulation treatment for patients with heart failure in sinus rhythm

Cochrane Database of Systematic Reviews

Evidence suggests neither anticoagulation (warfarin) nor antiplatelet therapy (aspirin) is better for mortality in systolic heart failure with sinus rhythm
(high quality evidence for all-cause mortality, moderate quality evidence for non-fatal CV and major bleeding events).

 

Testosterone treatment and risk of venous thromboembolism: population based case-control study

British Medical Journal

UK study (n=19 215 DVT/PE; 909,530 age matched controls) found starting testosterone linked to increased venous thromboembolism risk which peaked within 6 months (rate ratio 1.63; 95% CI, 1.12-2.37 corresponding to 10 additional cases above base rate) and declined thereafter.

 

Hormonal Contraception and Risk of Thromboembolism in Women With Diabetes

Diabetes Care

Study (146,080 women, 3,012 thromboembolic events) found rates of thromboembolism were highest among women on the contraceptive patch (16 per 1,000 woman-years) and lowest with intrauterine (6 per 1,000 woman-years) and subdermal (0 per 163 woman-years) contraceptives.

 

Optimal duration of dual antiplatelet therapy after acute coronary syndromes and coronary stenting

Heart

This article provides an overview of the evidence, current guidelines' recommendations and future perspectives on dual antiplatelet therapy (DAPT)
duration after an ACS and after coronary stenting. It proposes an algorithm of optimal duration of DAPT in these settings.

 

 

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

Von Willebrand’s Disease

New England Journal of Medicine

This is the most common inherited bleeding disorder. Review discusses latest findings on pathophysiology, diagnosis and treatment, which is based on normalising von Willebrand factor and factor VIII levels in case of bleeding or before an intervention.

 

Association between statin use and ischemic stroke or major haemorrhage in patients taking dabigatran for atrial fibrillation

Canadian Medical Association Journal

Results from two population based nested case control studies of over 45,000 patients show that simvastatin and lovastatin, when combined with dabigatran
etexilate, increased the risk of major haemorrhage, but not ischaemic stroke.

 

 

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:

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Conference report: Updated results from ongoing phase III RE-VERSE AD study on safety and efficacy of idarucizumab (Praxbind) in urgent situations

Biospace Inc.

In trial of 494 patients who had uncontrolled or life-threatening bleeding or required emergency surgery or an invasive procedure, primary endpoint of reversal of anticoagulant effect of dabigatran with 5g of idarucizumab within 4 hours was 100% Reversal was evident immediately.

 

Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy

Circulation

Study (n=2124) found either rivaroxaban 15 mg OD+P2Y12 inhibitor monotherapy or 2.5 mg rivaroxaban BD plus dual antiplatelet therapy (DAPT) was associated with a reduced risk of all-cause mortality/recurrent hospitalisation vs standard-of-care vitamin k antagonist+DAPT.

 

Warfarin utilisation and anticoagulation control in patients with atrial fibrillation and chronic kidney disease

Heart

Study (n=123188) found warfarin use decreased with increasing severity of chronic kidney disease (CKD) (57.2%–46.4%), but was higher in patients on dialysis (62.3%). Proportion of patients with time in range (TIR) ≥60% decreased with CKD severity; 21% on dialysis achieved TIR≥60%.

 

Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI

New England Journal of Medicine

The administration of either low-dose rivaroxaban (R)+P2Y12 inhibitor for 12 months or very-low-dose R+DAPT for 1, 6, or 12 months was associated with a
lower rate of clinically significant bleeding than was standard therapy with a vit K antagonist+DAPT for 1, 6, or 12 months.

 

Under-prescribing of Prevention Drugs and Primary Prevention of Stroke and Transient Ischaemic Attack in UK General Practice: A Retrospective Analysis

PLOS Medicine

UK study (n=29043) found >50% of people eligible for lipid-lowering, anticoagulant, or antihypertensive drugs were not prescribed them prior to first stroke/TIA. The authors estimate that around 12000 first strokes could be prevented/year annually through optimal prescribing.

 

Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients: An APEX Trial Substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban)

Circulation

This study (n=7513) reports that there were fewer all-cause strokes (0.54% v 0.97%; RR=0.56; P=0.032) and ischaemic strokes (0.48% v 0.91%; RR=0.53; P=0.026) among patients treated with betrixaban v enoxaparin through 77 days of follow-up.

 

Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial

European Heart Journal

Analysis of the TRACER trial (n=12,944) found that MI was associated with a greater risk of mortality compared with Bleeding Academic Research Consortium (BARC) 2 and 3a bleeding; a similar risk of mortality to BARC 3c bleeding; and a lower risk of mortality than BARC 3c bleeding.

 

Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease

New England Journal of Medicine

RCT (n=13,885) found that ticagrelor is not superior to clopidogrel for reducing cardiovascular events (10.8% vs 10.6%, HR 1.02, 95% CI 0.92-1.13). Major
bleeding occurred at similar rates (1.6% in both groups, HR 1.10, 95% CI 0.84-1.43).

 

CHMP issues positive opinion for lonoctocog alfa (Afstyla) for treatment and prophylaxis of bleeding in patients with haemophilia A

European Medicines Agency

Lonoctocog alfa is a single-chain recombinant human factor VIII product. It is proposed that the market authorisation extends to use in all age groups.

 

 

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

Association of Traditional Cardiovascular Risk Factors with Venous Thromboembolism: An Individual Participant Data Meta-analysis of Prospective Studies

Circulation

Meta-analysis (9 studies, n=255,865 with 4910 VTE events) found that apart from the association of cigarette smoking with provoked VTE, modifiable traditional CVD risk factors are not associated with increased risk. Higher systolic blood pressure was inversely associated with VTE.

 

Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial

The Lancet

This RCT (n=152) showed no significant difference between patients receiving nadroparin v placebo in the composite primary outcome-composite measure of
extension of calf DVT to proximal veins, contralateral proximal DVT and symptomatic PE at day 42 (3% vs 5% respectively, p=0.54).

 

 

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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