Ticagrelor for preventing atherothrombotic events after myocardial infarction: Appraisal consultation document

National Institute for Health and Care Excellence

DRAFT guidance supports use of ticagrelor 60mg, in combination with aspirin, as continuation therapy for preventing atherothrombotic events in people who
have a history of MI and a high risk of developing atherothrombotic events, only if certain criteria are met.

 

Sixteen-year nationwide trends in antithrombotic drug use in Denmark and its correlation with landmark studies

Heart

This paper provides nationwide data on long-term trends in antithrombotic use, noting it has doubled, mainly due to increased antiplatelet use and introduction of DOACs. Authors discuss how trends in use of individual drugs correlate with publication of landmark studies.

 

Occurrence of death and stroke in patients in 47 countries 1 year after presenting with atrial fibrillation: a cohort study

The Lancet

In this study evaluating 15,361 patients of whom 1758 (11%) died within 1 year, heart failure was the most common cause of death (30%) followed by stroke (8%). There were marked unexplained inter-regional variations in the occurrence of stroke and death.

 

Stability of International Normalized Ratios in Patients Taking Long-term Warfarin Therapy

Journal of the American Medical Association

Research letter describes a study of 3749 patients taking warfarin for atrial fibrillation which found that 26% had 80% or more INR values in the 2.0-3.0
range during the first 6 months. Of these patients, 34% continued to have stable INRs over the next 12 months.

 

Triple Oral Antithrombotic Therapy (TOAT) - A Teachable Moment

JAMA Internal Medicine

This review, based on a case vignette, discusses the use of TOAT, highlighting steps to reduce bleeding risk are advisable. These include prescribing a
proton pump inhibitor, using lower doses of antiplatelets, and avoiding high-potency P2Y12 inhibitors prasugrel and ticagrelor.

 

Comparison of Dabigatran versus Warfarin in Patients with Atrial Fibrillation and Valvular Heart Disease: The RE-LY Trial

Circulation

This review of the RE-LY trial found that the presence of VHD (n=3,950) did not influence the comparison of dabigatran with warfarin in terms of major bleed
rates and stroke and systemic embolism rates for both the 110mg and 150mg doses.

 

 

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

Self-monitoring and self-management of oral anticoagulation therapy

Cochrane Database of Systematic Reviews

Review of 28 RCTs (n=8,950) found a reduction in thromboembolic events in the pooled estimate of self-monitoring or self-management vs standard monitoring (HR, 0.58; 95%CI, 0.45-0.75). No reduction in all-cause mortality or incidence of major or minor haemorrhage was seen.

 

Economic burden of non-malignant blood disorders across Europe: a population-based cost study

The Lancet Haematology

Non-malignant disorders of the blood cost the 31 European countries €11 billion in 2012. Health-care costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for less than €1 billion (6%).

 

Heparin for the prevention of intraventricular haemorrhage in preterm infants

Cochrane Database of Systematic Reviews

There is very limited data on effect of prophylactic heparin on incidence and severity of intraventricular haemorrhage (IVH). Both the identified trials used
heparin in the context of maintaining umbilical line patency and not specifically to prevent germinal matrix IVH.

 

Impact of age on long-term anticoagulation and how gender and monitoring setting affect it: implications for decision making and patient management

British Journal of Clinical Pharmacology

Study (n=2094) found that frequency of warfarin dose changes and INR monitoring events declined until around age 67, then increased as patients got older.

 

Anticoagulation versus antiplatelet or no therapy in patients undergoing bioprosthetic valve implantation: a systematic review and meta-analysis

Heart

In a meta-analysis of 2 randomised and 12 observational studies, there was no benefit of adding a vitamin K antagonist (VKA) with regards to thromboembolism or mortality, versus antiplatelet /no therapy. However, use of a VKA was linked to increased risk of major bleeding.

 

Venous thromboembolism in medical patients during hospitalisation and 3 months after hospitalisation: a prospective observational study

BMJ Open

Australian study (n=986) found 54 (5.5%) developed venous thromboembolism (VTE), of which 25.9% (14/54) had detected VTE post-hospitalisation with increased risk if there was history of VTE, recent surgery and pulmonary conditions, suggesting potential role of thromboprophylaxis.

 

Evaluation of two new NICE indicators to help GPs and CCGs improve identification and management of atrial fibrillation (AF)

National Institute for Health and Care Excellence

In 2017, 30 UK GP practices will test these indicators. GPs will routinely test anyone >65 years for AF and assess how often someone with AF discusses treatment with GP. If these measures are found to improve AF identification/management, they could be rolled out in 2017/18.

 

 

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

Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registryDrug Safety Alert: Warfarin - reports of calciphylaxis (syndrome of vascular calcification)

Medicines and Healthcare products Regulatory Agency

An EU-wide review of relevant evidence recently concluded that there is a reasonable possibility that on rare occasions warfarin use might lead to calciphylaxis. Healthcare professionals are advised to consider stopping warfarin and starting appropriate treatment if necessary.

 

Management of bleeding with non–vitamin K antagonist oral anticoagulants in the era of specific reversal agents

Circulation

This review summarises the evidence around the management of non–vitamin K antagonist (NOACs)-related bleeding, including prevention of bleeding, general principles and supportive measures, nonspecific haemostatic agents, and NOAC-specific reversal agents.

 

Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry

European Heart Journal

Study (n=45,073) found the risk of the primary outcome (composite of all-cause death, re-admission with myocardial infarction or stroke) with ticagrelor vs. clopidogrel was 11.7 vs. 22.3% (HR 0.85 [95% CI: 0.78–0.93]).

 

 

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

Precision Medicine for Ischemic Stroke

JAMA Neurology

In this article, the authors discuss the future of precision medicine in the field of ischaemic stroke, first looking at the current status of genetic approaches, and then exploring the status of phenotype-based delineations.

 

Volunteers wanted to help determine the future of pharmacovigilance

Medicines and Healthcare products Regulatory Agency

Web-RADR: Recognising Adverse Drug Reactions is running a survey for healthcare providers, patients, and consumers of medicines to help develop the next generation of online side-effect reporting software.

 

New product: ALPROLIX (eftrenonacog alfa) powder and solvent for solution for injection

electronic Medicines Compendium

Eftrenonacog alfa is licensed for the treatment and prophylaxis of bleeding in patients with haemophilia B (congenital factor IX deficiency).

 

Direct oral anticoagulants: unique properties and practical approaches to management

Heart

This is a review of the indications and dosing considerations, clinical efficacy and safety, laboratory monitoring and reversibility considerations and peri-procedural management of the direct oral anticoagulants (DOACs), highlighting strategies to ensure safe and effective DOAC.

 

European Pharmacovigilance Risk Assessment Committee to begin review of factor VIII medicines for haemophilia A

European Medicines Agency

This review has been initiated following a recent study which suggested that inhibitors develop more frequently in patients on factor VIII (F-VIII) medicines made by DNA recombinant technology than in those receiving (F-VIII) derived from blood.

 

 

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

 

 

 

Risk of Bleeding and Thrombosis in Patients 70 Years Or Older Using Vitamin K Antagonists

JAMA Internal Medicine

Matched cohort study (n=3313) found compared to patients aged 70-79, those aged 80-89 had similar risk of bleeding, whereas those ≥90 had mildly increased risk of bleeding. Patients in their 80s and 90s had markedly higher risk of thrombosis vs. patients in their 70s.

 

Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack

Journal of the American Medical Association

Chinese study (n=2933) found after day 90 follow-up, clopidogrel-aspirin (CA) reduced the rate of new stroke in the non-carriers but not in carriers of loss-of-function alleles vs aspirin alone.

 

Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial

Circulation

In this analysis of ENGAGE AF-TIMI 48 study (n=14,071), findings from prespecified renal subgroups defined by a CrCl of 30-50 and >50mL/min were similar to overall trial results in which high dose edoxaban was comparable to warfarin for prevention of stroke/systemic embolism.

 

Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial

The Lancet Haematology

Analysis (n=771 with cancer) found recurrent venous thromboembolism (VTE) occurred in 4% of patients on edoxoban and 7% on warfarin (HR 0.53, 95% CI 0.28-1.00) concluding that edoxoban is non-inferior to warfarin in the treatment of patients with cancer with VTE.

 

Deep vein thrombosis and pulmonary embolism

The Lancet

This seminar focuses on the epidemiology, diagnosis, and treatment of deep vein thrombosis of the legs and pulmonary embolism as well as looking at future research in this area.

 

 

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

The association between non-vitamin K antagonist oral anticoagulants and gastrointestinal bleeding: a meta-analysis of observational studies

British Journal of Clinical Pharmacology

Meta-analysis of 8 cohort studies suggest a slightly higher risk of gastrointestinal bleeding with dabigatran use compared with warfarin (risk ratio 1.21; 95% CI, 1.05-1.39), but no significant difference was found between rivaroxaban and warfarin.

 

Major Bleeding and Hemorrhagic Stroke With Direct Oral Anticoagulants in Patients With Renal Failure: Systematic Review and Meta-Analysis of Randomized Trials

Chest

Study (n=94,897) found direct oral anticoagulants (DOACs) had decreased risk for major bleeding vs vitamin K antagonists when estimated creatinine clearance (eCrCL) 50-80mL/min (RR 0.87, 95%CI 0.81-0.93). However, DOACs' bleeding risk differs from each other when eCrCL<50mL/min.

 

On-Treatment Outcomes in Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights From ROCKET AF

Circulation

Analysis (n=12,612) found among those with on-treatment worsening renal function, rivaroxaban (RV) was linked to lower rates of stroke/systemic embolism vs. warfarin, without increase in composite bleeding endpoint. This was not seen in patients with stable renal function on RV.

 

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF

European Heart Journal

Two-year outcomes from ongoing, global observational study (n=17,162) found death was most frequent adverse outcome. Stroke-related mortality was not most frequent cause of death, suggesting that as well as anticoagulation, a more comprehensive approach to management is needed.

 

New "Aspirin-Guide" App for clinicians to help personalise decisions about aspirin use developed by Brigham and Women's Hospital researchers

Biospace Inc.

Researchers have developed a new, free mobile app, "Aspirin-Guide" that calculates both the CVD risk score and the bleeding risk score for individual patients, and helps clinicians decide which patients are appropriate candidates for the use of low-dose aspirin (75 - 81mg daily).

 

 

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

Stroke and death in elderly patients with atrial fibrillation in Japan compared with the United Kingdom

Heart

Study (n=3129) found elderly (age ≥75 years) patients with atrial fibrillation in both Japan and the UK are at similarly high risk of stroke and death. Appropriate oral anticoagulation was still underused (<60%) in both populations.

 

Eyes on Evidence: Perioperative anticoagulation for people with atrial fibrillation

National Institute for Health and Care Excellence

A commentary is provided on RCT in people with AF who stopped taking warfarin before elective surgery/invasive procedure, which found people who did not receive 'bridging' heparin had a lower risk of bleeding and no higher risk of thromboembolism than those who received it.

 

Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study

British Medical Journal

Danish cohort study (n=61,678) found all NOACs seem to be safe and effective alternatives to warfarin (WF) in a routine care setting. No significant difference was found for ischaemic stroke. Risks of death, any or major bleeding were lower for apixaban and dabigatran vs. WF.

 

Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial

British Medical Journal

In trial (n=18,201),~75% patients had polypharmacy; this subgroup had increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic/bleeding complications. Apixaban was more effective than warfarin regardless of number of concomitant drugs.

 

Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

The Lancet Neurology

Over 90% stroke burden (SB) is attributable to modifiable risk factors, and achieving control of behavioural/metabolic risk factors could avert over three-quarters of global SB. Air pollution has emerged as a significant contributor to SB especially in low/middle-income countries.

 

NIHR Signal: An anticoagulant, bivalirudin, may not be safer than the alternative, heparin, when unblocking arteries in the heart

National Institute for Health Research Signal

This is an expert commentary of a meta-analysis which found that bivalirudin as an alternative to heparin to prevent clotting during percutaneous coronary intervention may be ineffective in preventing recurrence of blockage or further heart attacks.

 

Prolonged dual antiplatelet therapy in stable coronary disease: comparative observational study of benefits and harms in unselected versus trial populations

British Medical Journal

The PEGASUS-TIMI-54 trial was one of first to inform management of high risk patients, but this analysis has shown that real world patients who survive ≥1 year after acute MI are at yet greater risk, amplifying potential of dual antiplatelet therapy to improve prognosis.

 

Risk of venous thromboembolism in cancer patients treated with epoetins or blood transfusions

British Journal of Clinical Pharmacology

Study of 69,888 patients identified 3316 cases of venous thromboembolism (VTE). There was a higher risk of VTE with epoetins (OR 1.31 (95% CI 1.03-1.65)), transfusions (2.33 (2.03-2.66)), and epoetins and transfusions (2.24 (1.34-3.77)).

 

Direct oral anticoagulants for stroke prevention in patients with atrial fibrillation: meta-analysis by geographic region with a focus on European patients

British Journal of Clinical Pharmacology

This review of 5 trials (n=72,673) found that direct oral anticoagulants were not superior to warfarin for prevention of stroke and systemic embolic events (RR=0.97 95% CI=0.85-1.11) in European patients (n=32,089), but were with patients from other regions (0.72, 0.63-0.83).

 

 

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

Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines

Gut

These guidelines refer to patients undergoing elective endoscopic gastrointestinal procedures, and make recommendations on the management antiplatelet/anticoagulant therapy based on the risk of procedural haemorrhage vs. thrombosis if therapy is discontinued.

 

Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: Executive summary—Revision 1

European Heart Journal

This guide has been updated including new information with a balanced guide in the areas where prospective data are still lacking. Changes include a discussion on the definition of 'non-valvular AF' and eligibility for DOAC therapy and finalised information on edoxaban.

 

Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis

The Lancet Neurology

Analysis (n= 6756 in 9 trials of alteplase vs. control) found that in alteplase group, net outcome is predicted both by time to treatment (faster time increasing % achieving excellent outcome) and stroke severity (more severe increasing absolute risk of intracerebral bleed).

 

One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial

British Medical Journal

Non-inferiority trial (n=518) found that stopping elastic compression stockings (ECS) after one year in compliant patients with proximal deep venous thrombosis (DVT) seemed not to be non-inferior to continuing ECS therapy for 2 years, with an NNT of 14.

 

Antithrombotic therapy in heart failure (HF) patients with and without atrial fibrillation (AF): update and future challenges

European Heart Journal

This review provides a perspective on the use of antithrombotic treatments in patients with both AF and HF, and in patients with HF and sinus rhythm, with particular attention to the NOACs, and provides background for therapeutic, outcome and trial improvement.

 

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

New England Journal of Medicine

In this RCT (n=7513), the primary efficacy outcome of composite asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism was not statistically significant (6.9% for betrixaban v 8.5% for enoxaparin in the group with raised d-dimer levels.

 

 

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

FDA approves Afstyla for patients with haemophilia A

PharmaTimes

Afstyla, a novel recombinant factor VIII single-chain therapy, designed for long-lasting protection from bleeds with 2-3 x weekly dosing. It can also be used as on-demand treatment to control bleeds, and in perioperative management of bleeding.

 

Cryptogenic Stroke

New England Journal of Medicine

This feature article begins with a case highlighting a common clinical problem, cryptogenic stroke. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.

 

Prediction of rates of thromboembolic and major bleeding outcomes with dabigatran or warfarin among patients with atrial fibrillation: new initiator cohort study

British Medical Journal

A comparison of bleeding rates seen in a cohort (n=21934) of patients with AF treated with warfarin v dabigatran with what was predicted using risk assessment models & data from RCTs showed good correlation between models & real-life but RCTs underestimate risk of major bleeding.

 

Reversal of the anticoagulant effect of dabigatran: idarucizumab (ESNM73)

National Institute for Health and Care Excellence

This review looks at the evidence for the efficacy/safety of idarucizumab for reversing the anticoagulant effect of dabigatran etexilate. There are
currently no other licensed agents to reverse the anticoagulant effect of dabigatran etexilate (or any other NOAC).

 

Individualising Duration of Dual Antiplatelet Therapy After Acute Coronary Syndrome or Percutaneous Coronary Intervention

Circulation

This review, based on 2 case vignettes, discusses dual antiplatelet therapy in the management of patients with acute coronary syndromes and those undergoing percutaneous coronary intervention, in the context of balancing optimal duration with the risk of adverse bleeding effects.

 

Use of antipsychotics and risk of myocardial infarction: a systematic review and meta-analysis

British Journal of Clinical Pharmacology

This review of 9 observational studies found that the odds for developing an MI were higher with antipsychotic users vs never users (OR=1.88, 95%CI=1.39-2.54). Short term users (<30 days) and those with schizophrenia had a more pronounced risk.

 

The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis

European Heart Journal

This review of 12 studies (n=99,996) found that non-paroxysmal AF was associated with higher rates of thromboembolism than parosxysmal AF (unadjusted RR=1.355, 95%CI= 1.169-1.571).

 

 

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

Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials

The Lancet

Data from 12 trials (n=15,778) found aspirin reduced 6 week risk of recurrent ischaemic stroke (IS) vs. placebo by ~ 60% (HR 0.42, 95% CI, 0.32–0.55, p<0.0001) and disabling or fatal IS by ~70% (0.29, 0.20–0.42, p<0.0001), with greatest benefit in patients with TIA/minor stroke.

 

Coronary-Artery Bypass Grafting

New England Journal of Medicine

This review covers evidence from trials of CABG vs. medical therapy or vs. percutaneous coronary intervention, as well as complicating factors, indications and evaluation for CABG, morbidity and mortality, and secondary prevention.

 

Which Oral Anticoagulant for Atrial Fibrillation?

Journal of the American Medical Association

This Medical Letter review summarises the newly available oral anticoagulants and compares them with commonly prescribed warfarin.

 

Should prophylactic doses of low molecular weight heparins be used in patients with renal impairment?

South West Medicines Information & Training

This updated Medicines Q&A reviews the current literature regarding the use of prophylactic doses of low molecular weight heparins in patients with renal impairment.

 

 

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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