CHMP issues positive opinion on licensing of vorapaxar (Zontivity) in EU

European Medicines Agency

Vorapaxar 2mg film tablet is intended for the reduction of atherothrombotic events in adult patients with a history of MI and should be co-administered with aspirin, and where appropriate, with clopidogrel.

 

Six-month versus 24-month dual antiplatelet therapy after implantation of drug eluting stents in patients non-resistant to aspirin: ITALIC, a randomized multicenter trial

Journal of the American College of Cardiology

This RCT, terminated early due to recruitment problems (n=2031 of planned 2475) found rates of bleeding and of thrombotic events were not significantly different for 6- vs. 24-month dual antiplatelet therapy after PCI with new-generation DES in aspirin responders.

 

Percutaneous Left Atrial Appendage Closure vs Warfarin for Atrial Fibrillation: A Randomized Clinical Trial

Journal of the American Medical Association

This study found mechanical left atrial appendage closure to be non-inferior and superior to warfarin in patients with nonvalvular AF and CHADS2 score ≥1 in preventing the combined outcome of stroke, systemic embolism and CV death (rate of 2.3 v 3.8 events per 100 patient-years).

 

Interim data on dabigatran versus warfarin for AF in routine care

Biospace Inc.

An interim analysis of two health insurance databases show that patients with non-valvular AF treated with dabigatran had a lower rate of major haemorrhage (354 v 395 events; HR 0.75) and stroke (62 v 69; HR 0.77, not statistically significant) vs. those receiving warfarin.

 

Ponatinib (Iclusig▼): risk of vascular occlusive events

Medicines and Healthcare products Regulatory Agency

An EU review on the risk of serious vascular occlusive events with ponatinib has been completed. The available evidence shows that the risk is likely to be dose-dependent; however the data are insufficient to recommend reducing the ponatinib dose.

 

Relation of Nonsteroidal Anti-inflammatory Drugs to Serious Bleeding and Thromboembolism Risk in Patients With Atrial Fibrillation Receiving Antithrombotic Therapy: A Nationwide Cohort Study

Annals of Internal Medicine

In patients with AF receiving anticoagulants, exposure to NSAIDs increased the risk of serious bleeding (additional 1.9 events per 1000 patients). The majority of events (38.7%) were gastrointestinal; 18.9% were intracranial. Thromboembolism risk was also increased.

 

Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate

Circulation

In this randomised, placebo-controlled Phase 1 study (n=110), a 4-factor prothrombin complex concentrate reversed the effects of edoxaban on bleeding duration following punch biopsy in a dose-dependent manner, with complete reversal observed following 50 IU/kg.

 

Effects of Golden Hour Thrombolysis: A Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) Substudy

JAMA Neurology

The availability of a stroke emergency mobile unit increased rates of thrombolysis overall (32.6% v 22% with conventional care; P<0.001) and the rates delivered within the first 'golden hour' after symptom onset (31.0% v 4.9%; P<0.01). Short-term mortality rates were similar.


Controversies in cardiovascular medicine – pre-treatment with P2Y12 inhibitors in NSTEMI

Circulation

Two linked articles discuss whether pre-treatment with P2Y12 inhibitors in Non–ST-segment–elevation acute coronary syndrome is clinically justified.

 

Extended duration dual antiplatelet therapy and mortality: a systematic review and meta-analysis

The Lancet

This analysis of 14 trials that randomised participants to different durations of dual antiplatelet therapy (DAPT) did not find any difference in all-cause, cardiovascular (CV) or non-CV mortality between extended duration and short-duration DAPT (≤6 months) or aspirin alone.

 

Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents

New England Journal of Medicine

Patients with a drug-eluting stent who continued dual antiplatelet therapy >1 year had a lower risk of stent thrombosis and major adverse cardiovascular and cerebrovascular events, but increased all-cause mortality (secondary endpoint; HR 1.36; 95% CI, 1.00 to 1.85; P=0.05).

 

 

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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Development of investigational antibody MEDI2452 for reversal of antiplatelet effects of ticagrelor

Biospace Inc.
A pre-clinical development program is evaluating the ability of MEDI2452 to rapidly and specifically reverse the antiplatelet effects of ticagrelor in emergency situations that cause major bleeding, such as surgery.

 

Anticoagulant therapy during primary percutaneous coronary intervention for acute myocardial infarction: a meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors

British Medical Journal

In patients with STEMI undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor (GPI) and LMWH plus GPI were most efficacious in terms of avoiding major adverse cardiovascular events in the short-term; bivalirudin was associated with the lowest bleeding risk.

 

Platelet Transfusion: A Clinical Practice Guideline From the AABB

Annals of Internal Medicine

These US guidelines provide pragmatic recommendations on the appropriate use of platelet transfusion (prophylactic and therapeutic) in adults, based on the best available published evidence.

 

Vitamin K for Patients with High International Normalized Ratios (INRs): Safety

Canadian Agency for Drugs and Technologies in Health

A limited literature search identified one non-randomised study which found that withholding warfarin or giving vitamin K treatment to patients on oral anticoagulants who have an INR >9 did not effectively reduce the INR within 24 hours.

 

RAC recommends further assessment of risk of developing inhibitors with Kogenate Bayer/Helixate NexGen (factor VIII)

European Medicines Agency

The PRAC is recommending further examination of the available evidence for Kogenate Bayer/Helixate NexGen, as new evidence has shown it may be associated with a higher risk of inhibitor (antibody) development than other FVIII products in treatment-naïve haemophilia patients.

 

 

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 PER977 to Reverse the Anticoagulant Effect of Edoxaban

New England Journal of Medicine

In double-blind, placebo-controlled dose escalation trial in 80 healthy people given 60mg edoxaban, baseline haemostasis was restored from anticoagulated state in 10-30 minutes after administration of 100-300 mg of PER977 and was sustained for 24 hours. Phase 2 studies underway.

 

Costs and Benefits of Antithrombotic Therapy in Atrial Fibrillation in England: An Economic Analysis based on GRASP-AF

NHS Improving Quality

53.6% suitable patients (pts) in England are on anticoagulants. If warfarin prescribed for all of above with CHA2DS2-VASc ≥2, further 11,600 AF-related CVAs would be averted/year, with additional 1500 excess bleeds, and decrease in number of deaths in AF pts over 1-year by 3500.

 

Secondary Prevention of Cardiovascular Disease With Vorapaxar: A New Era of 3-Drug Antiplatelet Therapy?

JAMA Internal Medicine

The authors of this viewpoint article discuss the risks and benefits of vorapaxar and conclude that although it has a potential role in the secondary prevention of cardiovascular disease, they remain sceptical of its widespread use as part of a 3-drug antiplatelet regimen.

 

Medicines Evidence Commentary : Non-steroidal anti-inflammatory drugs and risk of venous thromboembolism

National Institute for Health and Care Excellence

A systematic review and meta-analysis of observational studies found that there was a statistically significantly increased risk of venous thromboembolism (VTE) among users of NSAIDs compared to non-users of NSAIDs. However, the meta-analysis has a number of important limitations.

 

Oral anticoagulation therapy after radiofrequency ablation of atrial fibrillation and the risk of thromboembolism and serious bleeding: long-term follow-up in nationwide cohort of Denmark

European Heart Journal

This study reports a relatively low risk of VTE beyond 3 months after radiofrequency ablation for AF. The authors suggest the risk of bleeding with oral anticoagulation may outweigh benefits in this setting, but randomised studies are required to confirm their findings.

 

Risk of Bleeding With Dabigatran in Atrial Fibrillation

JAMA Internal Medicine

This analysis of Medicare patients who started warfarin (n=8102) or dabigatran (n=1302) within 60 days of AF diagnosis reports that dabigatran was associated with a higher risk of overall, major and GI bleeding (HR 1.30, 1.58 and 1.85 v warfarin) but lower risk of ICH (HR 0.32).

 

European Medicines Agency accepts Marketing Authorisation Application for ELOCTA™ (rFVIIIFc) for haemophilia A

Biospace Inc.

The EMA has validated an application seeking approval of Elocta™, a recombinant factor VIII Fc fusion protein product candidate for the treatment of haemophilia A. The application includes results from the A-LONG and Kids A-LONG Phase III studies.

 

 

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

 

 

Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated with Dabigatran or Warfarin for Non-Valvular Atrial Fibrillation

Circulation

Retrospective cohort study in general practice found dabigatran linked to reduced risk of ischaemic stroke, intracranial bleed, and death, and increased risk of major GI bleed vs. warfarin in elderly patients with non-valvular AF. These links more pronounced with 150mg BD dose.

 

Effect of intermittent pneumatic compression on disability, living circumstances, quality of life, and hospital costs after stroke: secondary analyses from CLOTS 3, a randomised trial

The Lancet Neurology

RCT (n=2876) found despite previously reported decrease proximal DVT risk at 30 days (primary endpoint), there were no significant differences in disability, living circumstances, or health-related QoL in patients using or not using intermittent pneumatic compression.

 

Deep vein thrombosis, pulmonary embolism - dabigatran etexilate (treatment, prevention): final appraisal determination

National Institute for Health and Care Excellence

DRAFT guidance recommends dabigatran etexilate, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults.

 

Common Questions and Answers on the Practical Use of Oral Anticoagulants in Non-Valvular Atrial Fibrillation

UKMi
This document highlights key factors influencing anticoagulant choice, identification of patients taking anticoagulants, when might warfarin be the preferred option, and active swapping from warfarin to novel agents.

 

FDA advisory panel recommends approval of edoxaban 60mg in selected AF patients

Reuters
Advisory panel to FDA has recommended approval of 60 mg dose of edoxaban, a once-daily anticoagulant that inhibits Factor Xa, for use in patients with AF, but only in those with mild renal impairment, as outcomes vs. warfarin were worse in those with normal renal function.

 

FDA Approves Obizur (Antihaemophilic Factor (Recombinant), Porcine Sequence) for Acquired Haemophilia A

US Food and Drug Administration
The US FDA has approved Obizur (Antihaemophilic Factor (Recombinant), Porcine Sequence) for the treatment of bleeding episodes in adults with acquired haemophilia A.

 

 

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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Acute coronary syndrome - rivaroxaban [ID532]: consultation document

National Institute for Health and Care Excellence

DRAFT guidance recommends rivaroxaban as option, in combination with aspirin plus clopidogrel/aspirin alone, for preventing atherothrombotic events in people who have had an ACS with elevated cardiac biomarkers. Risk of bleeding should be assessed before treatment is started.

 

Chronic vitamin K antagonist therapy and bleeding risk in ST elevation myocardial infarction patients

Heart

In patients with STEMI treated with primary PCI, chronic use of vitamin K antagonist (VKA) was associated with an increased risk of in-hospital major bleed (17.0% v 10.1% in those not on VKA). In those on VKA, glycoprotein inhibitors were associated with increased bleeding risk.

 

New product: Nuwiq (human coagulation factor VIII, simoctocog alfa)

electronic Medicines Compendium

Nuwiq is licensed for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). Dose and duration depend on the severity of the factor VIII deficiency, location and extent of the bleeding and the patient's clinical condition.

 

 

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

New product: Xarelto (rivaroxaban) 2.5 mg film-coated tablets

electronic Medicines Compendium
Rivaroxaban co-administered with aspirin alone or with aspirin plus clopidogrel or ticlopidine, is indicated for prevention of atherothrombotic events in adult patients after an ACS with elevated cardiac biomarkers.

 

Guideline for the diagnosis and management of the rare coagulation disorders

British Journal of Haematology
This guideline covers the diagnosis and management of patients with rare coagulation disorders, defined as monogenic bleeding disorders caused by deficiency of a soluble coagulation factor or factors, other than von Willebrand disease, Haemophilia A or Haemophilia B.

 

dabigatran etexilate (Pradaxa)

Scottish Medicines Consortium
The SMC has accepted dabigatran etexilate (Pradaxa®) for use within NHS Scotland for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. Cost-effectiveness of longer-term use (>18 months) is uncertain.

 

 

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 in adults with congenital heart disease: The who, the when and the how?

Heart

This article reviews the current use of anticoagulation in patients with congenital heart disease. It discusses treatment and monitoring with warfarin, heparin and the new oral anticoagulants, and who and when to treat.

 

Medicines Evidence Commentary : Acute coronary syndromes: duration of dual antiplatelet therapy after drug-eluting stent implantation

National Institute for Health and Care Excellence

A randomised controlled trial reported that continuing dual antiplatelet therapy beyond a year after stent implantation did not statistically significantly reduce the risk of the combined outcome of death or cardiovascular events compared with continuing aspirin monotherapy....

 

 

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

Underrepresentation of Women, Elderly Patients, and Racial Minorities in the Randomized Trials Used for Cardiovascular Guidelines

JAMA Internal Medicine

The authors of this research letter report that women, elderly patients, and those of non-white racial backgrounds are underrepresented in the RCTs of US (ACC/AHA) guidelines for AF, HF, and ACS, raising concerns about their applicability in these populations.

 

Optimal Duration of Low Molecular Weight Heparin for the Treatment of Cancer-Related Deep Vein Thrombosis: The Cancer-DACUS Study

Journal of Clinical Oncology

The results of this study suggest that in patients with cancer treated with LMWH for 6 months for a first DVT, continuation for a further 6 months in those with residual vein thrombosis did not reduce the rate of recurrent VTE. Those without RVT at 6 months are a low risk group.

 

Sex Differences in Short-term and Long-term All-Cause Mortality Among Patients With ST-Segment Elevation Myocardial Infarction Treated by Primary Percutaneous Intervention: A Meta-analysis

JAMA Internal Medicine

This meta-analysis of observational studies suggests that women with STEMI treated with primary PCI have a higher risk of in-hospital mortality than men; this association is likely however to be confounded by baseline CV risk factors and differences in clinical profile.

 

Ministry of Health, Labour and Welfare in Japan approves edoxaban for additional indications

Biospace Inc.

The oral factor Xa inhibitor edoxaban has been approved in Japan for the prevention of ischaemic stroke and systemic embolism in patients with non-valvular AF and for treatment and secondary prevention of VTE. It is currently under regulatory review in the EU for these indications.

 

Drug Therapy for Chronic Thromboembolic Pulmonary Hypertension: A Review of the Comparative Clinical Effectiveness

Canadian Agency for Drugs and Technologies in Health

This article reviews current evidence of comparative efficacy and safety of monotherapy or combination medical interventions for patients with chronic thromboembolic pulmonary hypertension. Studies of riociguat, bosentan and sildenafil are summarised.

 

Non-adherence to cardiovascular medications

European Heart Journal

The authors of this review on non-adherence to cardiovascular medications, which is increasingly recognised, conclude that in the face of a rapidly expanding population at risk for CHD, effective means of ensuring patient adherence to evidence-based therapy are urgently needed.

 

All Wales Advice on the Role of Oral Anticoagulants

All Wales Medicines Strategy Group

This updated document covers the safe and effective use of oral anticoagulants for the prevention of stroke and systemic embolism in people with non-valvular AF. It considers assessment, drug choice, review, prescribing responsibility, and INR monitoring for warfarin.

 

 

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-steroidal anti-inflammatory drugs and risk of venous thromboembolism: a systematic review and meta-analysis

Rheumatology

Meta-analysis of 6 observational studies (21,401 VTE events) noted statistically significant increased VTE risk among NSAID users (pooled risk ratio 1.80; 95% CI, 1.28, 2.52). Results should be interpreted with caution due to observational nature of studies and other limitations.

 

Chronic Kidney Disease and Bleeding Complications After Intravenous Thrombolytic Therapy for Acute Ischemic Stroke

Circulation

Analysis of data on 44,410 patients with ischaemic stroke treated with IV tPA found those with CKD had higher risk of symptomatic intracranial or serious systemic haemorrhage, but presence of renal impairment not independently linked to these major complications of IV tPA use.

 

Atrial fibrillation and heart valve disease: self monitoring coagulation status using point of care coagulometers (the CoaguChek XS system and the INRatio2 PT/INR monitor) – guidance (DG14)

National Institute for Health and Care Excellence

In this guidance, NICE recommends the use of two point-of care coagulometers (CoaguChek XS and InRatio2 PT/INR) for patients on long term vitamin K antagonist therapy who have AF or heart valve disease, provided they or their carer are able to self monitor effectively.

 

Electronic Medication Packaging Devices and Medication Adherence: A Systematic Review

Journal of the American Medical Association

This review of 37 studies of electronic medication packaging devices (adherence-monitoring devices incorporated into the packaging of a prescription medication) concluded that higher quality evidence is needed to determine the effects of these interventions on non-adherence.

 

2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes

Circulation

This is a full revision of the 2007 guideline for the management of unstable angina and NSTEMI. It incorporates both established and new evidence from published clinical trials, as well as information from basic science and comprehensive review articles.

 

The Postthrombotic Syndrome: Evidence-Based Prevention, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association

Circulation

This scientific statement provides an overview of the post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis, and offers practical recommendations for its optimal prevention, diagnosis, and management.

 

 

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

 

Clinical and Safety Outcomes Associated With Treatment of Acute Venous Thromboembolism: A Systematic Review and Meta-analysis

Journal of the American Medical Association

Analysis found no differences in efficacy/safety with most treatment strategies used to treat VTE compared with the LMWH–vitamin K antagonist, except UFH–vitamin K antagonist which was associated with an increased rate of recurrent VTE.

 

Medicines Evidence Commentary : Antithrombotic treatment for people with atrial fibrillation and stable coronary artery disease

National Institute for Health and Care Excellence

A Danish observational study found that adding antiplatelet therapy (aspirin, clopidogrel or both) to anticoagulant treatment with a vitamin K antagonist such as warfarin, was not associated with a reduced risk of recurrent coronary events or of thromboembolism, but was associated with increased bleeding.

 

Medicines Evidence Commentary : Atrial fibrillation : differences among patients and physicians in values and preferences about antithrombotic choice

National Institute for Health and Care Excellence

A Spanish study found a wide range of views among patients and physicians on the acceptable trade-off between a reduction in risk of stroke and an increased risk of bleeding in 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