Recent Advances in Antidotes for Direct Oral Anticoagulants: Their Arrival Is Imminent

Canadian Journal of Cardiology

Several antidotes for direct oral anticoagulants are being developed and recently presented data have raised hopes that their introduction into clinical practice is imminent. In this article, the authors review the latest advances in their development.

 

FDA approves first long-acting recombinant coagulation Factor IX concentrate (Alprolix) for patients with haemophilia B

Biospace Inc.

This has been approved in US for control and prevention of bleeding episodes, perioperative management and routine prophylaxis, in patients with haemophilia B. It was developed using Fc fusion and thus has a more prolonged circulation in body which extends time between infusions.

 

Lack of Concordance between Empirical Scores and Physician Assessments of Stroke and Bleeding Risk in Atrial Fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry

Circulation

This analysis of 10,094 AF patients found little agreement between provider-assessed risk and empirical stroke and bleeding risk scores in AF. These differences may partly explain current divergence of anticoagulation treatment decisions from guideline recommendations.

 

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation

Circulation

These US guidelines for management of atrial fibrillation cover: • Pathophysiology • Clinical evaluation: • Prevention of thromboembolism • Rate control • Rhythm control • Specific patient groups • Evidence gaps and future research directions

 

Combined oral contraceptives: venous thrombosis

Cochrane Database of Systematic Reviews

All COCs investigated in this analysis were linked to increased risk of VTE. The effect size depended both on progestogen used and dose of ethinylestradiol (EE). Thus COCs with lowest possible dose of EE and good compliance should be prescribed, i.e. 30 μg EE with levonorgestrel.

 

Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial

The Lancet

In women with 1 or 2 losses, there was no difference in live birth rate (309/535 for aspirin vs 286/543 for placebo; p=0•0984). However, in women with 1 loss at less than 20 weeks gestation, there was a significant difference (151/242 for aspirin vs 133/250 for placebo; p=0•0446)

 

Vibropulse for cellulitis or venous leg ulcers

Midlands Medicines

This is an evidence based summary of Vibropulse™, a device that utilises cycloidal vibration therapy and is prescribable on an FP10 for cellulitis or venous leg ulcers. The review concludes that there are currently insufficient data in this area to recommend its use.

 

 

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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Five-Year Survival in Patients with ST-Segment Elevation Myocardial Infarction According to Modalities of Reperfusion Therapy: The French Registry on Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) 2005 Cohort

 

Circulation

 

This analysis of registry data reports 5-year survival following STEMI of 88% for patients receiving fibrinolysis, 83% for PCI and 59% for no reperfusion. The authors suggest a pharmaco-invasive strategy constitutes a valid alternative to PCI on a nationwide scale.

 

 

Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial

 

European Heart Journal

 

This analysis of data from 779 pts experiencing major bleeding during ROCKET AF found administration of fresh frozen plasma and prothrombin complex concentrates was less frequent in the rivaroxaban arm. Use of transfused packed RBC and outcomes were however similar to 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

 

Factor Xa Inhibitors vs Warfarin for Preventing Stroke and Thromboembolism in Patients With Atrial Fibrillation

Journal of the American Medical Association

Based on a Cochrane review, this JAMA Clinical Evidence Synopsis concludes that compared with warfarin, factor Xa inhibitors are associated with a lower risk of stroke and systemic embolic events and fewer rates of intracranial haemorrhage and mortality in patients with AF.

 

Subdural haematoma in the elderly

British Medical Journal

This article on subdural haematoma is one of a series highlighting conditions that may be more common than many doctors realise or may be missed at first presentation. It covers how common it is, why it is missed and why this matters, and its diagnosis and management.

 

The young patient with asymptomatic atrial fibrillation: what is the evidence to leave the arrhythmia untreated?

European Heart Journal

This review summarises epidemiological data on young AF, efficacy, and limitations of rate and rhythm control in young patients, information on arrhythmia progression and outcome, and the consequences of these data for AF treatment in young, asymptomatic 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

 

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

European Heart Journal

This 3-yr study (n=8709 on zotarolimus-eluting stent [ES]/sirolimus-ES) suggests dual antiplatelet therapy (DAPT) use influenced rate of stent thrombosis to a different extent, depending upon type of implanted DES; and optimal duration of DAPT will likely depend upon stent type.

 

The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service.
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Describing deprescribing

Drug and Therapeutics Bulletin

This article discusses increasing multimorbidity and polypharmacy amongst the population and the risks associated with these factors. The article highlights that stopping prescribing or "deprescribing" is an important consideration in the medicines optimisation process.

 

Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial

The Lancet

Elastic compression stockings (ECS) did not prevent post-thrombotic syndrome after 1st proximal DVT [incidence of PTS=14.2% in active ECS vs 12.7% in placebo (adjusted HR 1.13, 95% CI 0.73-1.76; p=0.58)]. The authors state the findings do not support routine ECS use post DVT.

 

Warfarin, Kidney Dysfunction, and Outcomes Following Acute Myocardial Infarction in Patients With Atrial Fibrillation

Journal of the American Medical Association

This cohort study (n=24,317) found that warfarin (vs. none) was linked to lower 1-year risk for composite of death, MI, and ischaemic stroke without higher risk of bleeding in consecutive acute MI patients with AF. This association was not related to severity of concurrent CKD.

 

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 apixaban compared with aspirin in patients who previously tried but failed treatment with vitamin K antagonists: results from the AVERROES trial

European Heart Journal

In this prespecified analysis, the efficacy and safety of apixaban compared with aspirin was consistent in subgroups of patients who had previously attempted but failed vitamin K antagonist therapy (n=2216), irrespective of the reason for discontinuation.

 

Nonsteroidal Anti-Inflammatory Drugs and the Heart

Circulation

This evidence based review discusses the mechanisms underlying the cardiovascular effects of traditional NSAIDs and coxibs.

 

Sentinel Stroke National Audit Programme (SSNAP) clinical audit, July - September 2013 public report

Royal College of Physicians

This report finds that huge improvements have been made in the quality of stroke care and services over the past years as measured by previous national stroke audits and it is anticipated that similar improvements will be demonstrated through future SSNAP quarterly reports.

 

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

Revised SPC: Pletal (cilostazol) 50 mg and 100 mg tablets

Electronic Medicines Compendium

Indication restricted to 2nd line use. 4.2: specialist initiation/review after 3 months. 4.2, 4.4 & 4.5: Reduce dose to 50mg BD if with strong CYP3A4 inhibitors 4.3 & 4.4: New contraindications and warnings, including concomitant use with 2 or more anticoagulants/antiplatelets.

 

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

Electronic Medicines Compendium

The SPC has been updated with warning about increased risk of bleeding with concomitant use of SSRIs and clopidogrel.

 

Outcomes of Temporary Interruption of Rivaroxaban Compared with Warfarin in Patients with Nonvalvular Atrial Fibrillation: Results from ROCKET AF

Circulation

Risk of a Thrombotic Event after the 6-Week Postpartum Period Analysis of ROCKET AF trial (n=14,236) found that temporary interruptions (3-30 days) of oral anticoagulation is common and associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin.

 

Risk of a Thrombotic Event after the 6-Week Postpartum Period

New England Journal of Medicine

This US study (n=1,687,930;1015 thrombotic events) reported elevated thrombosis risk that persisted until at least 12wks post delivery, though absolute risk increase after 6wks was low. Risks/benefits of continuing treatment for high-risk women after 6 wks require investigation.

 

Dabigatran (Pradaxa) lawsuits in US due to start in August

NewsDaily

US courts are scheduled to start hearing cases in August against Boehringer Ingelheim, who is facing more than 2000 lawsuits over claims that dabigatran caused severe and fatal bleeding. Claimants accuse Boehringer of not having sufficiently warned of these risks.

 

Treatment of Venous Thromboembolism

Journal of the American Medical Association

This review of the aetiology of VTE and the 3 phases of VTE treatment (acute, long-term and extended) concludes that further study to understand individual patient risks is needed to make ideal treatment decisions.

 

How effective is tranexamic acid for acute gastrointestinal bleeding?

British Medical Journal

This article on tranexamic acid for the treatment of acute GI bleeding is one of a series that highlight areas of practice where management lacks convincing supporting evidence. The authors discuss the available evidence and make recommendations, in light of the uncertainty.

 

Drug Safety Update: Combined hormonal contraceptives and venous thromboembolism: review confirms risk is small

Medicines and Healthcare products Regulatory Agency

A review of the latest evidence on the risk of thromboembolism in association with combined hormonal contraceptives (CHCs) has concluded that the risk of blood clots with all low dose CHCs is small and the benefits of CHC far outweigh the risk of serious side effects.

 

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

 

 

Cost-effectiveness of apixaban vs. current standard of care for stroke prevention in patients with atrial fibrillation

This analysis estimates that apixaban has an incremental cost-effectiveness ratio of £11,909 per QALY gained compared with warfarin (in VKA suitable patients) and £7,196 per QALY gained compared with aspirin (in VKA unsuitable patients) for stroke prevention in AF. This analysis estimates that apixaban has an incremental cost-effectiveness ratio of £11,909 per QALY gained compared with warfarin (in VKA suitable patients) and £7,196 per QALY gained compared with aspirin (in VKA unsuitable patients) for stroke prevention in AF.

http://eurheartj.oxfordjournals.org/content/early/2014/02/07/eurheartj.ehu006.abstract

 

Guidelines for the Prevention of Stroke in Women: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

This statement summarises data on stroke risk factors that are unique to (reproductive factors) and more common (migraine with aura, obesity, metabolic syndrome, and AF) in women than men, and expands on data provided in prior guidelines for women.

http://stroke.ahajournals.org/content/early/2014/02/06/01.str.0000442009.06663.48.abstract

 

Meta-Analysis of Risk of Stroke or Transient Ischemic Attack With Dabigatran for Atrial Fibrillation Ablation

A meta-analysis (18 observational studies; n= 5513) found that dabigatran during AF ablation is associated with a higher risk of thromboembolic complications compared to warfarin (16 vs 7 events; OR 2.81, 95% CI 1.23 to 6.45) with no significant differences for major bleeding.

http://www.sciencedirect.com/science/article/pii/S0002914914000538

 

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

 

 

Direct oral anticoagulants in the treatment and long-term prevention of venous thrombo-embolism 

This article reviews direct oral anticoagulants (e.g. apixaban, dabigatran and rivaroxaban) under the following topic headings: Acute and long-term treatment of VTE; Extended treatment of VTE; Lessons from the developmentprogrammes for these drugs; and practical considerations.

http://eurheartj.oxfordjournals.org/content/early/2014/02/06/eurheartj.ehu027.abstract

 

Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack

PPAR- agonists were found to reduce recurrent stroke and total events of CV death, non-fatal MI or non-fatal stroke, and improve insulin sensitivity and stabilisation of carotid plaques, but findings should be interpreted cautiously due to small number and quality of the studies.

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010693.pub2/full

 

Point-of-care coagulometers (the CoaguChek XS system and the INRatio2 PT/INR monitor) in people on long-term vitamin K
antagonist therapy who have atrial fibrillation or heart valve disease: diagnostics consultation document

Draft guidance from NICE's Diagnostics Assessment Programme on two technologies for self-monitoring the clotting of blood in people on long term anticoagulation therapy has been issued for public consultation.

http://www.nice.org.uk/nicemedia/live/14091/66497/66497.pdf

 

Aspirin versus vitamin K antagonist treatment guided by transoesophageal echocardiography in patients with atrial fibrillation: a pilot study

The results of this study (n=238) suggest that transoesophageal echocardiography (TEE) may help to refine stroke risk and guide antithrombotic treatment choice (VKA or aspirin) in patients with paroxysmal atrial fibrillation. Further research is however required.

http://heart.bmj.com/content/early/2014/01/30/heartjnl-2013-305017.abstract

 

Ultrasound-assisted thrombolysis for acute pulmonary embolism: a systematic review

The authors of this review discuss catheter-based revascularisation for PE and ultrasound-assisted thrombolysis and present and discuss the results of seven studies (n=197) of ultrasound-assisted catheter-directed thrombolysis (CDT) for PE (only one small RCT).

http://eurheartj.oxfordjournals.org/content/early/2014/02/03/eurheartj.ehu029.abstract

 

Media hype blood clot risk of birth control pills

This 'Behind the Headlines' assessment discusses the risk of venous thromboembolism associated with use of combined oral contraceptives
(following the recent European review) and comments that the UK media overhyped the potential risk in their reporting.

http://www.nhs.uk/news/2014/02February/Pages/Media-hype-blood-clot-risk-of-birth-control-pills.aspx

 

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

 

 

Antiplatelet Therapy for Stable Coronary Artery Disease in Atrial Fibrillation Patients on Oral Anticoagulant: A Nationwide Cohort Study

This study of 8,700 patients with AF and stable CAD (>12 months from an acute event) found combined vitamin K antagonist (VKA) plus antiplatelet was not associated with a reduced risk of MI/coronary death or thromboembolism vs. VKA monotherapy, but bleeding risk was increased.

http://circ.ahajournals.org/content/early/2014/01/27/CIRCULATIONAHA.113.004834.abstract

 

Risk of drug-induced liver injury with the new oral anticoagulants: systematic review and meta-analysis

This analysis of 29 RCTs (n=152,116, mean follow-up 16 months) found that NOACs were not linked to increased risk of drug-induced liver injury (RR 0.90, 95% CI, 0.72 to 1.13, I2=0%). Similar results were obtained for individual NOACs.

http://heart.bmj.com/content/early/2014/01/29/heartjnl-2013-305288.abstract

 

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