Items filtered by date: February 2021

Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration adverse event reporting system

British Journal of Clinical Pharmacology

Reports of drug-induced liver injury associated with NOACs including acute liver failure events represented 3.7% (n = 146) and 1.7% (n = 222) of all reports for rivaroxaban and dabigatran, respectively. Disproportionality signals emerged for rivaroxaban in primary analysis.

 

Bleeding, Recurrent Venous Thromboembolism, and Mortality Risks During Warfarin Interruption for Invasive Procedures

JAMA Internal Medicine

This retrospective cohort study of patients whose warfarin therapy was interrupted for invasive diagnostic or surgical procedures (total 1812) found use of bridging increased the rate of clinically relevant bleeding (2.7% v 0.2% in those with no bridging); VTE rates were similar.

 

Standard vs Modified Antiplatelet Preparation for Preventing Thromboembolic Events in Patients With High On-Treatment Platelet Reactivity Undergoing Coil Embolization for an Unruptured Intracranial Aneurysm: A Randomized Clinical Trial

JAMA Neurology

This single-centre study reports that in patients undergoing coiling for unruptured aneurysms, use of a modified antiplatelet regimen for those with high on-treatment platelet reactivity reduced the rate of thromboembolic events vs. standard antiplatelet therapy.

 

Longer Versus Shorter Duration Dual-Antiplatelet Therapy After Drug-Eluting Stent Placement: A Systematic Review and Meta-analysis

Annals of Internal Medicine

This review of 9 RCTs reports that longer-duration dual antiplatelet therapy (DAPT) following drug-eluting stent placement reduced MI risk (RR 0.73, 95% CI 0.58-0.92) but increased mortality (1.19, 1.04-1.36) and major bleeding risk (1.63, 1.34-1.99]) vs. shorter-duration DAPT.

 

 

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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Risk of Substantial Intraocular Bleeding With Novel Oral Anticoagulants: Systematic Review and Meta-analysis

JAMA Oncology

Analysis of 17 RCTs suggests no differences exist in the risk of substantial intraocular bleeding between NOACs and other antithrombotic drugs (vitamin K antagonists, aspirin, low-molecular-weight heparin). However, the number of events was scarce so further studies are needed.

 

Stroke Prevention in Atrial Fibrillation: A Systematic Review

Journal of the American Medical Association

This review highlights that stroke prevention is central to management of AF, irrespective of a rate or rhythm control strategy. Following the initial
focus on identifying low-risk patients, all others with 1 or more stroke risk factors should be offered oral anticoagulation.

 

The Association of Discharge Aspirin Dose With Outcomes After Acute Myocardial Infarction: Insights From the TRANSLATE-ACS Study

Circulation

US study of 10,213 MI patients who underwent PCI and were discharged on dual antiplatelet therapy found that high maintenance dose aspirin (325mg) was linked to similar rates of major adverse cardiovascular events but greater risk of minor bleeding vs. low-dose aspirin (81mg).

 

Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis

Circulation

Direct oral anticoagulants demonstrate at least equal efficacy to VKAs in managing thrombotic risks in the elderly although bleeding patterns were distinct with dabigatran linked to a particularly higher risk of GI bleeding compared to VKAs.

 

The prognostic utility of tests of platelet function for the detection of ‘aspirin resistance’ in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation

National Institute for Health Research

This systematic review evaluated whether or not 'aspirin resistance' defined using platelet function tests (PFTs) was linked to occurrence of adverse clinical outcomes and concluded that studies investigating this were of inconsistent quality - no firm conclusions could be made.

 

Efficacy of Prophylactic Low–Molecular Weight Heparin for Ambulatory Patients With Advanced Pancreatic Cancer: Outcomes From the CONKO-004 Trial

Journal of Clinical Oncology

In patients with advanced pancreatic cancer undergoing chemotherapy, prophylactic enoxaparin was associated with a reduced rate of symptomatic VTE (6.4% vs 15.1% with no enoxaparin) and no increase in major bleeding; there was no difference in progression-free or overall survival.

 

 

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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Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation

European Heart Journal

RCT (n=248; VENTURE-AF) found that use of uninterrupted rivaroxaban was feasible and bleeding and thromboembolic event rates were similar to those for uninterrupted vitamin K antagonists in patients with non-valvular atrial fibrillation undergoing catheter ablation.

 

Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a subgroup analysis of the ENGAGE AF-TIMI 48 trial

European Heart Journal

In pre-specified subgroup analysis, patients randomised to lower dose edoxaban (DE) who were taking amiodarone at baseline had fewer ischaemic events compared with warfarin vs. patients not on amiodarone. Also amiodarone had no effect on relative efficacy and safety of higher DE.

 

 

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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50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study

The Lancet

In this analysis (202,417 person-yrs), a roughly 4-times increase in age-adjusted incidence and prevalence of AF in both sexes was reported. Risk of AF in both sexes doubled with each decade of age, and risk of stroke and death after diagnosis were equivalent between the sexes.

 

Antiplatelet therapy following transcatheter aortic valve implantation

Heart

Systematic review and pooled analysis of individual patient data (n=672) found no difference in 30-day net adverse clinical and cerebral events rate between aspirin-only or dual antiplatelet therapy following transcatheter aortic valve implantation.

 

Oral Anticoagulation, Aspirin, or No Therapy in Patients With Nonvalvular AF With 0 or 1 Stroke Risk Factor Based on the CHA2DS2-VASc Score

Journal of the American College of Cardiology

Study (n=39,400) found low-risk patients (CHA2DS2-VASc=0 [male],1 [female]) have a truly low risk for stroke and bleeding. With 1 additional stroke risk factor (score 1 & 2 respectively), there was significant increase in event rates (particularly mortality) if non-anticoagulated.

 

Gender differences in the effect of cardiovascular drugs: a position document of the Working Group on Pharmacology and Drug Therapy of the ESC

European Heart Journal

This position paper discusses the gaps in knowledge on the effects of gender on pharmacokinetics and pharmacodynamics of cardiovascular drugs, and how such differences may influence their effectiveness and safety.

 

Low-Molecular-Weight Heparin for Women With Unexplained Recurrent Pregnancy Loss: A Multicenter Trial With a Minimization Randomization Scheme

Annals of Internal Medicine

In 449 women with unexplained recurrent pregnancy loss, a daily injection of LMWH (dalteparin 5000IU) for up to 24 weeks' gestation did not improve the rate of ongoing pregnancy at 24 weeks (86.8% v 87.9%) or the live birth rate (86.0% v 86.7%) v control.

 

EMA approves Raplixa™ powdered fibrin sealant for surgical bleeding

European Medicines Agency

The EMA has approved Raplixa™ (fibrin sealant) for use in adults as a supportive treatment where standard surgical techniques are insufficient for improvement of haemostasis. It must be used in combination with an approved CE marked gelatin sponge (supplied separately).

 

 

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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Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study

British Medical Journal

A US analysis of almost 220 000 new users of dabigatran, rivaroxaban, or warfarin (2010-2013) found that risk of GI bleeding with dabigatran or rivoroxaban was similar to warfarin but risk exceeded that of warfarin with age, particularly in those over 75 years.

 

Risk of gastrointestinal bleeding associated with oral anticoagulants: population based retrospective cohort study

British Medical Journal

A US analysis (n= 46,000) found that neither dabigatran nor rivaroxaban was associated with a statistically significantly increased risk of GI bleeding relative to warfarin. However the study had wide confidence intervals and an increased risk of bleeding cannot be ruled out.

 

 Positive CHMP opinion for edoxaban (Lixiana™) for prevention of stroke and systemic embolism in atrial fibrillation and treatment and prevention of deep vein thrombosis and pulmonary embolism

European Medicines Agency

The CHMP has adopted a positive opinion recommending approval of edoxaban (Lixiana™), for prevention of stroke and systemic embolism in adults with atrial fibrillation and for treatment and prevention of deep vein thrombosis and pulmonary embolism.

 

 

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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FDA grants priority review to Biologics License Application for idarucizumab

Biospace Inc.

Idarucizumab, a humanised antibody fragment, is being investigated to specifically reverse the anticoagulant effect of dabigatran in patients needing emergency intervention or experiencing an uncontrolled or life-threatening bleeding event.

 

Rates of hospitalization among patients with deep vein thrombosis before and after the introduction of rivaroxaban

Hospital Pharmacy

Retrospective claims analysis (n=134, rivaroxaban [RV], n=536 historical LMWH/warfarin-treated patients) found availability of RV reduced
hospitalisation rate in patients with DVT treated with RV vs. what it would have been if only LMWH/warfarin were available (60% vs. 82%).

 

Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis

National Institute for Health Research

No new trials were located; the review was therefore largely based on the evidence available for TA182 (TRITON-TIMI 38 trial). A new economic model confirmed prasugrel is likely to be a cost-effective treatment option when compared with clopidogrel for all subgroups considered.

 

 

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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Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials

British Medical Journal

Meta-analysis (10 RCT's; n=32 287) found that short term DAPT (<12 months) after drug eluting stent implementation reduced bleeding with no apparent increase in ischaemic complications vs standard 12 month duration, and could be considered for most patients.

 

Acute Stroke Intervention: A Systematic Review

Journal of the American Medical Association

Systematic review (n = 108 082) found that IV thrombolysis remains the standard of care for patients with moderate to severe neurological deficits who present within 4.5 hours of symptom onset.

 

Prevalence and antithrombotic management of atrial fibrillation in hospitalised patients

Heart

US study (n=812) identified high AF prevalence rates (16.8%) across all wards. Most patients with AF were at high risk for stroke; however anticoagulation therapy was considered inappropriate in 48.7%, indicating the need for guideline optimisation especially in non-cardiac wards.

 

Site-Level Variation in and Practices Associated With Dabigatran Adherence

Journal of the American Medical Association

US study (n= 4863) reported wide variability in medication adherence in patients with nonvalvular AF treated with dabigatran. Pharmacist-led monitoring was associated with higher adherence rates as was pharmacist collaboration with clinicians for nonadherant patients.

 

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

National Institute for Health and Care Excellence

Discussion of a RCT which found that continuing dual antiplatelet therapy beyond 12 months after drug-eluting stent implantation reduced the risk of stent thrombosis, and major cardiovascular and cerebrovascular events at 30 months, compared with switching to 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

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FDA files supplemental New Drug Application for dabigatran (Pradaxa®) for the prophylaxis of DVT and PE following hip replacement surgery

Biospace Inc.

The US FDA has filed an application seeking approval of dabigatran for the prophylaxis of DVT and PE in patients who have had primary elective total hip replacement surgery, based on the results of two Phase III trials (RE-NOVATE and RE-NOVATE II) comparing it to enoxaparin.

 

Investigational anticoagulant reversal agent (PER977) receives FDA Fast Track designation

Biospace Inc.

The FDA has granted Fast Track status for PER977, an investigational anticoagulant reversal agent that directly binds to NOACs, fondaparinux, low molecular weight heparins and unfractionated heparins. It is undergoing development as an IV injection; Phase III studies are planned.

 

Eyes on Evidence: Detecting atrial fibrillation in people who have had a stroke

National Institute for Health and Care Excellence

A commentary is provided on 2 RCTs which reported that long-term ECG monitoring was more effective at detecting AF than 24-hour or intermittent ECG monitoring in people who had experienced apparent cryptogenic stroke or transient ischaemic attack.

 

Antiphospholipid syndrome: A patient’s journey

British Medical Journal

This is last in a series of occasional articles by patients about their experiences that offer lessons to doctors. It illustrates the often long delays
experienced by patients before a diagnosis is made and treatment started.

 

Association Between Perioperative Low-Molecular-Weight Heparin vs Unfractionated Heparin and Clinical Outcomes in Patients With Cancer Undergoing Surgery

Journal of the American Medical Association

Based on 16 trials (n=12 890) there was no difference between LMWH and unfractionated heparin in their associations with mortality, pulmonary embolism, symptomatic DVT, major bleeding, or minor bleeding outcomes in patients with cancer undergoing surgical procedures.

 

Practice Guide for managing a high INR in a patient on warfarin

British Medical Journal

This practice guide, based on a case vignette, outlines the immediate and long-term management of a patient presenting with a high INR whilst on
warfarin.

 

CADTH reviews point-of-care INR testing compared with laboratory INR testing

Canadian Agency for Drugs and Technologies in Health

This review summarises the practical impact of, and cost effectiveness of point-of-care (POC) INR testing compared with lab INR testing concluding that patient self-management (POC INR testing + dose adjustment) may be the most cost-effective option, when feasible, in Canada.

 

 

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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Safety of Intravenous Thrombolysis in Stroke Mimics: Prospective 5-Year Study and Comprehensive Meta-Analysis

Stroke

Shortening door-to-needle time may lead to inadvertent intravenous thrombolysis (IVT) administration in stroke mimics (SMs). Prospective, single-centre experience (n=75) coupled with findings of meta-analysis of 9 studies suggest safety of IVT in SMs.

 

Duration of dual antiplatelet therapy after coronary artery stenting: where is the sweet spot between ischaemia and bleeding?

European Heart Journal

The article discusses dual antiplatelet therapy (DAPT), stable coronary artery disease, acute coronary syndromes, novel evidence, stent types and DAPT, rebound after DAPT cessation, and individualised DAPT management.

 

Cangrelor (Kengrexal™) approved in the EU for use in patients undergoing PCI

Biospace Inc.

The EC has granted marketing authorisation for cangrelor (Kengrexal™) for the reduction of thrombotic cardiovascular events in adults with coronary artery disease undergoing PCI and who have not received an oral P2Y12 inhibitor prior to the procedure.

 

 

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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Association between brain imaging signs, early and late outcomes, and response to intravenous alteplase after acute ischaemic stroke in the third International Stroke Trial (IST-3): secondary analysis of a randomised controlled trial

The Lancet Neurology

Pre-specified analysis (n=3017) found some early ischaemic and pre-existing signs are linked to reduced independence at 6 months and increased symptomatic intracranial haemorrhage. No interaction was noted between brain imaging signs and effects of alteplase on these outcomes.

 

Rivaroxaban for preventing adverse outcomes after acute management of acute coronary syndrome – guidance (TA 335)

National Institute for Health and Care Excellence

Rivaroxaban is recommended as an option within its marketing authorisation, in combination with aspirin plus clopidogrel or aspirin alone, for preventing atherothrombotic events in people who have had an acute coronary syndrome with elevated cardiac biomarkers.

 

Precision medicine to improve use of bleeding avoidance strategies and reduce bleeding in patients undergoing percutaneous coronary intervention: prospective cohort study before and after implementation of personalized bleeding risks

British Medical Journal

US data reported that pre-procedural risk stratification was associated with an increase in the uptake of bleeding avoidance strategies (bivalirudin, radial approach, and vascular closure devices) leading to a reduction in rates of bleeding, particularly among high risk patients.

 

Microbleeds, Mortality, and Stroke in Alzheimer Disease: The MISTRAL Study

JAMA Neurology

This longitudinal cohort study found that microbleeds in patients with Alzheimer disease increased the risk of CV events (non-lobar bleeds) and stroke (lobar bleeds) and related mortality – even higher risks for such events were found in patients using antithrombotics.

 

 

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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