European CHMP recommends granting of marketing authorisation for idarucizuma (Praxbind) as antidote to dabigatran

European Medicines Agency

Idarucizuma is a specific reversal agent for dabigatran and is intended for use in adults when rapid reversal is required for emergency surgery/urgent procedures; or in life-threatening or uncontrolled bleeding. It is proposed that use be restricted to hospital only.

 

Edoxaban for preventing stroke and systemic embolism in people with non valvular atrial fibrillation – guidance (TA355)

National Institute for Health and Care Excellence

NICE recommends the use of edoxaban as an option for preventing stroke and systemic embolism in adults with non-valvular atrial fibrillation with one or more risk factors. The decision about whether to start treatment with edoxaban should be made after an informed discussion.

 

 

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

An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers, Editor’s Capsule Summary

Annals of Emergency Medicine

Study (n=243) found bleeding after ingestion of Xa inhibitor is uncommon. Prothrombin time, APTT, or INR may be elevated in minority of cases but appears unreliable to measure bleeding risk. Massive acute ingestion in suicides may result in significant anticoagulation.

 

Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis

Open Heart

Meta-analysis of 39 studies suggests that the controversial interaction between PPIs and clopidogrel seen in in-vitro studies has no clinical significance. Rather, patients on PPIs have higher burden of comorbidities and thus most likely have increased risk for adverse CV events.

 

FDA approves recombinant Factor VIII (Nuwiq®) for the treatment of Haemophilia A

Biospace Inc.

The FDA has approved Nuwiq® for the treatment of adults and children with Haemophilia A. This is the first B-domain deleted recombinant Factor VIII derived from a human cell-line, not chemically modified or fused with another protein, designed for the treatment of this population.

 

Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke

Cochrane Database of Systematic Reviews

Risk was only increased in women using COCs containing ≥ 50 µg of estrogen. When combined with results of studies on risk of venous thrombosis in COC users, it seems that the COC pill containing levonorgestrel and 30 µg of estrogen is safest oral form of hormonal contraception.

 

 

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

Diagnostic prediction models for suspected pulmonary embolism: systematic review and independent external validation in primary care

British Medical Journal

Five diagnostic prediction models to rule out PE were evaluated for transportability to primary care in a cohort of 598 patients. Although efficiency was similar (43-48%), the three Wells rules performed better than the revised Geneva models for safety (failure rate 1.2% v 3.1%).

 

The CHA2DS2-VASc score for stroke risk stratification in patients with atrial fibrillation: a brief history

European Heart Journal

The CHA2DS2-VASc score is now recommended in many guidelines for stroke risk stratification in AF. The article discusses the evolution of this scoring system.

 

 

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

Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials

European Heart Journal

In high-risk patients with prior MI, dual antiplatelet therapy (DAPT) for >1 year decreased the risk of major adverse cardiovascular events and CV death versus aspirin alone, with no difference in overall mortality. Major bleeding, but not fatal bleeding, was increased with DAPT.

 

Strategies for thromboprophylaxis in Fontan circulation: a meta-analysis

Heart

his meta-analysis of 10 studies (n=1,200) found aspirin or warfarin prophylaxis reduced the risk of thromboembolic events in patients who underwent the Fontan procedure; there was no significant difference between the two agents.

 

A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan

European Heart Journal

The Absorb bioresorbable vascular scaffold was deemed non-inferior to cobalt-chromium everolimus-eluting stents in terms of target lesion failure at 12 months (incidence of 4.2% vs 3.8%, respectively) in patients with one or two de novo lesions in different epicardial vessels.

 

Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes

New England Journal of Medicine

In patients with ACS for whom PCI was anticipated, bivalirudin was associated with a similar rate of major adverse CV events to unfractionated heparin (10.3% v 10.9%; RR 0.94; 95% CI 0.81 to 1.09; P=0.44). A post-PCI bivalirudin infusion did not appear to be of any benefit.

 

How to Monitor Patients Receiving Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation

Annals of Internal Medicine

This evidence-based practice tool, endorsed by Thrombosis Canada, the Canadian Stroke Consortium, the Canadian Cardiovascular Pharmacists Network and the Canadian Cardiovascular Society, aims to help healthcare professionals provide best-practice anticoagulant follow-up care.

 

XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation

European Heart Journal

This study investigating the safety and efficacy of rivaroxaban in routine clinical use reported that rates of stroke and major bleeding were low in patients receiving rivaroxaban in routine clinical practice (0.7 and 2.1 events per 100 patient-years respectively).

 

The Efficacy and Safety of Vorapaxar With and Without a Thienopyridine for Secondary Prevention in Patients with Prior Myocardial Infarction and no History of Stroke or TIA: Results from TRA 2 P-TIMI 50

Circulation

Pre-specified analysis (n=16,897) found vorapaxar (VX) significantly reduced composite of CV death, MI and stroke vs. placebo, regardless of planned thienopyridine (TP) therapy. Moderate/severe bleeding risk was increased with VX and was not significantly altered by planned TP.

 

Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study

European Heart Journal

Retrospective study (n=2244) found discontinuation of platelet inhibitor 3 days before surgery, as opposed to 5 days, did not increase the incidence of major bleeding complications in ticagrelor-treated patients, but increased the incidence in clopidogrel-treated patients.

 

Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation

Journal of the American Medical Association

Cohort study (n=42,987) found that among patients with incident heart failure with/without AF, CHA2DS2-VASc score was linked to risk of ischaemic stroke, thromboembolism, and death. However, predictive accuracy was modest and clinical utility of score remains to be determined.

 

Effect of clopidogrel with aspirin on functional outcome in TIA or minor stroke: CHANCE substudy

Neurology

This subgroup analysis suggests that clopidogrel plus aspirin vs. aspirin alone improves 90-day functional outcome (poor functional outcome occurred in 254 [9.9%] on combination vs 299 [11.6%] on aspirin alone; p=0.046) in patients with acute minor stroke or TIA.

 

Bispecific antibody ACE910 assigned ‘breakthrough’ designation in US for prophylactic treatment of haemophilia A patients who have developed factor VIII inhibitors

PharmaTimes

ACE910 is an investigational humanised bispecific monoclonal antibody engineered to mimic the function of blood coagulation factor VIII, and thus provide a new approach to treating the condition, regardless of whether patients have developed inhibitors.

 

Ticagrelor approved in US for long-term use in patients with acute coronary syndrome or a history of myocardial infarction

PharmaTimes

FDA approval of long term use is based on data from PEGASUS TIMI-54 study, which showed that in patients on aspirin with MI more than 1 year previously, treatment with ticagrelor significantly reduced risk of CV death, MI, or stroke (but increased risk of major bleeding).

 

 

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

Edoxaban for treating and for preventing deep vein thrombosis and pulmonary embolism – guidance (TA354)

National Institute for Health and Care Excellence
NICE recommends edoxaban, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults.

 

Medication Initiation Burden Required to Comply with Heart Failure Guideline Recommendations and Hospital Quality Measures

Circulation

This US-based study (n=158,992; 271 hospitals) suggests 22% of patients admitted for HF require initiation of at least 1 medicine; research into benefits of mass initiation of medications prior to discharge v sequential initiation extending into the ambulatory setting is needed.

 

 

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

Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial

Journal of the American Medical Association

In patients with active cancer and proximal DVT or PE, there was no statistically significant difference between tinzaparin and warfarin for recurrent VTE (6-month incidence 7.2% v 10.5%; P=0.07) or mortality; clinically relevant non-major bleeding was lower with tinzaparin.

 

Longer-term results of recombinant factor IX therapy in haemophilia B

Biospace Inc.

Interim results from the phase III B-YOND open-label extension study support the long-term safety and efficacy of an investigational recombinant clotting factor IX therapy (Alprolix®) in the treatment of severe haemophilia B for up to two years.

 

Does warfarin interact with oseltamivir or zanamivir?

UKMi

This updated Medicines Q&A evaluates the available evidence for an interaction between warfarin and oseltamivir or zanamivir.

 

Is it safe to take herbal medicines with non-vitamin K antagonist oral anticoagulants (NOACs)?

UKMi

This new Medicines Q&A evaluates the available evidence for the safety of co-administering herbal medicines with the non-vitamin K antagonist oral anticoagulants (NOACs).

 

Long working hours and risk of coronary heart disease and stroke: a systematic review and meta-analysis of published and unpublished data for 603 838 individuals

The Lancet

Review of 25 studies from 24 cohorts in Europe, US, and Australia found employees who work long hours (≥55 h/week) have a higher risk of stroke (RR 1.33,95% CI,1.11–1.61;p=0.002) than those working standard hours (35–40h/week); the link with CHD is weaker (1.13;1.02–1.26;p=0.02).

 

Prothrombin complex concentrate for reversal of vitamin K antagonist treatment in bleeding and non-bleeding patients

Cochrane Database of Systematic Reviews

Four RCTs (high risk of bias; underpowered) suggest prothrombin complex concentrate does not appear to reduce mortality or transfusion requirements but demonstrates possibility of reversing vitamin K-induced coagulopathy without need for transfusion of fresh frozen plasma.

 

 

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 and Outcomes of Triple Therapy Among Older Patients With Acute Myocardial Infarction and Atrial Fibrillation

Journal of the American College of Cardiology

Analysis (n=4959) found that ~ 1 in 4 older AF patients undergoing PCI for MI were discharged on triple therapy; and those receiving triple therapy vs. dual antiplatelet therapy had higher rates of major bleeding without a measurable difference in composite MI, death, or stroke.

 

Optimizing the Safe Use of Direct Oral Anticoagulants in Older Patients: A Teachable Moment

JAMA Internal Medicine

Case of 86-year-old woman with AF who presents with persistent epistaxis and found to have supratherapeutic levels of rivaroxaban and creatinine clearance of 21 mL/min highlights challenge of ensuring appropriate and safe use of direct oral anticoagulants in frail older patients.

 

Recanalization Therapies in Acute Ischemic Stroke Patients: Impact of Prior Treatment with Novel Oral Anticoagulants on Bleeding Complications and Outcome - A Pilot Study

Circulation

The results of this observational study suggest IV thrombolysis or intra-arterial treatment in carefully selected patients with an ischaemic stroke who are taking NOACs may not be associated with an excessive risk of intracranial haemorrhage; further data are however required.

 

Oral dual antiplatelet therapy: what have we learnt from recent trials?

European Heart Journal

This paper outlines the evidence base for clinical decisions regarding timing of initiation and duration of dual antiplatelet therapy in acute coronary syndrome.

 

Pregnancy Complicated by Venous Thrombosis

New England Journal of Medicine

This clinical practice article starts with a case vignette of a pregnant women presenting with venous thrombosis. The author's recommendations are based on supporting evidence and guidelines.

 

Hemostatic efficacy, safety and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease

Blood

In patients with severe type 1, 2, or 3 von Willebrand disease, a recombinant von Willebrand factor (initially administered together with recombinant Factor VIII) led to excellent or good control in 96.9% of 192 treated bleeds, with a single infusion effective in 81.8%.

 

Atrial fibrillation (non-valvular) - edoxaban tosylate [ID624]: final appraisal determination

National Institute for Health and Care Excellence

In DRAFT guidance (final appraisal determination), NICE recommends edoxaban, within its marketing authorisation, as an option for preventing stroke and systemic embolism in adults with non-valvular atrial fibrillation with one or more of the stated risk factors.

 

Venous thromboembolic diseases - management (Standing Committee B update): addendum consultation

National Institute for Health and Care Excellence

This DRAFT guideline update includes new recommendations on use of systemic thrombolysis in patients with 'intermediate-risk' pulmonary embolism, and on long-term use of compression stockings for the prevention of post-thrombotic syndrome in patients who have had a proximal 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

Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study

British Medical Journal

RCT (n=12 552) found that compared to those not anticoagulated, warfarinised patients had more days at home (as opposed to institutional care) during 2-years after discharge and a reduced risk of major adverse cardiovascular events and recurrent ischaemic stroke.

 

FDA accepts for review biologics license application for rVIII-SingleChain therapy for haemophilia A

Biospace Inc.

rVIII-SingleChain has a strong affinity for von Willebrand factor, leading to greater stability and integrity of FVIII in circulation. In the pivotal clinical trial, it met all primary endpoints.

 

Outcomes with prolonged clopidogrel therapy after coronary stenting in patients with chronic kidney disease

Heart

In this cohort of 4880 patients undergoing drug-eluting stents, clopidogrel (CL) use of 12 months after PCI was linked to lower risks of death/MI (18% v 24%, HR=0.74) and death v patients with normal renal function, supporting a patient-centred approach to prolonging CL after PCI.

 

 

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

Cangrelor for reducing atherothrombotic events in people undergoing percutaneous coronary intervention or awaiting surgery requiring interruption of anti platelet therapy (terminated appraisal) – technology appraisal guidance (TA351)

National Institute for Health and Care Excellence

NICE is unable to make a recommendation about the use in the NHS of cangrelor for reducing atherothrombotic events in people undergoing PCI or awaiting surgery requiring interruption of anti-platelet therapy because no evidence submission was received from The Medicines Company.

 

Genotype-guided drug prescribing: a systematic review and meta-analysis of randomized control trials

British Journal of Clinical Pharmacology

This meta-analysis of fifteen studies (n=5688; 19 drugs) reports a statistically significant benefit in favour of genotype-guided warfarin dosing to achieve time in therapeutic INR, resulting in reduction in warfarin-related minor and major bleeding and thromboembolisms.

 

Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of deep vein thrombosis

Cochrane Database of Systematic Reviews

Review of 11 RCTs (n=27,945) deemed to be of high methodological quality and low risk of bias found that NOACs may be an effective and safe alternative to conventional anticoagulation treatment for acute DVT.

 

Lixiana®▼(Edoxaban): risk minimisation resources

Daiichi Sankyo

Educational materials have been developed to help manage important risks such as bleeding associated with edoxaban (ED) use. Clinicians should familiarise themselves with these materials before prescribing ED and ensure all patients familiarise themselves with Patient Alert Card.

 

Primary prophylaxis for venous thromboembolism in patients undergoing cardiac or thoracic surgery

Cochrane Database of Systematic Reviews

There is limited evidence on efficacy and safety. Data for important outcomes such as PE or major bleeding were often lacking. Give uncertainties around benefit-to-risk balance, no conclusions can be drawn and case-by-case risk evaluation of VTE and bleeding remains preferable.

 

Comparison of the Short-Term Risk of Bleeding and Arterial Thromboembolic Events in Nonvalvular Atrial Fibrillation Patients Newly Treated With Dabigatran or Rivaroxaban versus Vitamin K Antagonists: A French Nationwide Propensity-Matched Cohort Study

Circulation

In this study of 19,713 vitamin K antagonists (VKA), 8,443 dabigatran and 4,651 rivaroxaban new users, no statistically significant difference in bleeding or thromboembolic risk was observed between newer oral anticoagulants users and VKA new users in non-valvular AF patients.

 

Independent expert review concludes alteplase is safe and effective for use within existing treatment guidelines

Medicines and Healthcare products Regulatory Agency

Following questions about the safety of alteplase, and the methodology used in trials assessing it, an expert working group of the UK's Commission on Human Medicines (CHM) has concluded that alteplase is safe and effective for use up to 4.5 hours after the onset of symptoms.

 

 

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

rivaroxaban (Xarelto®)

Scottish Medicines Consortium

The SMC does not recommend use of rivaroxaban (co-administered with aspirin ± clopidogrel or ticlopidine) within NHS Scotland for the prevention of atherothrombotic events in adults after an acute coronary syndrome with elevated cardiac biomarkers.

 

tinzaparin sodium (Innohep®)

Scottish Medicines Consortium

The SMC has accepted tinzaparin for use within NHS Scotland for the extended treatment of symptomatic VTE and prevention of its recurrence in patients with solid tumours. This advice takes account of the benefits of a Patient Access Scheme that improves its cost-effectiveness.

 

Peri-procedural management of patients taking oral anticoagulants

British Medical Journal

This review summarises the pharmacology of oral anticoagulants (OA) relevant to the peri-procedural period, and reported outcomes of peri-procedural management of oral anticoagulants used for therapeutic purposes.

 

Choice of Estimated Glomerular Filtration Rate Equation Impacts Drug-Dosing Recommendations and Risk Stratification in Patients With Chronic Kidney Disease Undergoing Percutaneous Coronary Interventions

Journal of the American College of Cardiology

This study, aimed at identifying which equation is superior in estimating GFR for predicting adverse outcomes after PCI, supports use of CKD-EPI equation for risk stratification and calls for standardisation in estimation of GFR for studies to improve dosage recommendations.

 

Deep vein thrombosis, pulmonary embolism (treatment, secondary prevention) - edoxaban tosylate: final appraisal determination

National Institute for Health and Care Excellence

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

 

Intracranial Hemorrhage After Ischemic Stroke: Incidence, Time Trends, and Predictors in a Swedish Nationwide Cohort of 196 765 Patients

Circulation: Cardiovascular Quality and Outcomes

Incidence of intracranial hemorrhage within 1-year after stroke was ≈2%/year at risk, about 15 times higher vs. reference population. Risk increased within first 30 days but decreased thereafter. Thrombolysis, but not increased use of antithrombotics/statins, affected risk.

 

Androgen Deprivation Therapy for Prostate Cancer and the Risk of Venous Thromboembolism

European Urology

Cohort study (n=21,729 of whom 609 hospitalised for VTE) found current (vs. non) use of androgen deprivation therapy was linked to 84% increased relative risk of VTE (incidence rates:10.1 vs 4.8/1000 person-years;HR:1.84;95% CI,1.50–2.26), whereas there was no link with past use.

 

Heparin-Induced Thrombocytopenia

New England Journal of Medicine

Treatment of acute heparin-induced thrombocytopenia (HIT) requires the cessation of heparin and initiation of therapeutic-dose anticoagulation with an alternative agent (argatroban, danaparoid, fondaparinux, or bivalirudin). Warfarin should be avoided in patients with acute HIT.

 

Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study

British Medical Journal

This analysis of a Korean nationwide health insurance database found combined use of antidepressants and NSAIDs was associated with an increased risk of intracranial haemorrhage within 30 days versus use of antidepressants without NSAIDs (hazard ratio 1.6, 95% CI 1.32 to 1.85).

 

Oral anticoagulants for stroke prevention in atrial fibrillation: current status, special situations, and unmet needs

The Lancet
This paper addresses the role of anticoagulation for stroke prevention in AF in the era of NOACs, with a focus on special situations including management in the event of bleeding and around the time of procedures including cardioversion, catheter ablation, and device implantation.

 

Pharmacology of antithrombotic drugs: an assessment of oral antiplatelet and anticoagulant treatments

The Lancet
This paper focuses on the pharmacological properties of the most commonly used oral antithrombotic drugs (aspirin, P2Y12 receptor antagonists, other targets, vitamin K antagonists, and non-VKA 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

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