Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial

The Lancet Haematology

RCT (n=500) reports fewer symptomatic recurrent venous thromboembolism rates with rivaroxaban: 1% of 335 children receiving weight-adjusted rivaroxaban vs 3% of 165 receiving standard anticoagulants (HR 0.40, 95% CI 0.11–1.41), with similar rates of bleeding in both groups.

 

 

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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Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery The FIBRES Randomized Clinical Trial

Journal of the American Medical Association

RCT of 735 adults who underwent CABG surgery and developed significant bleeding and hypofibrinogenemia post surgery showed similar number of blood components transfused within 24hrs with both fibrinogen concentrate group and cryoprecipitate group (p<0.01 for non-inferiority).

 

Management of Nonvariceal Upper Gastrointestinal Bleeding (UGIB): Guideline Recommendations From the International Consensus Group

Annals of Internal Medicine

Recommendations for patients receiving anticoagulation or antiplatelet therapy have been updated. PPI therapy is recommended to prevent UGIB in patients with previous ulcer bleeding who are receiving single- or dual-antiplatelet or anticoagulant therapy.

 

Prevalence and Knowledge of Potential Interactions Between Over‐the‐Counter Products and Apixaban

Journal of the American Geriatrics Society

Survey (n=791,California) found significant number of patients take OTC meds (particularly dietary supplements) with potentially serious interactions (SIs) with apixaban (33% took ≥1 and 6.7% multiple interacting OTC meds) and they appear to lack knowledge about potentially SIs.

 

Safety and efficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention

European Heart Journal

Review (4 RCTs; n= 10 234) reported lower major or clinically relevant non-major bleeding with double vs. triple antithrombotic therapy (RR 0.66, 95% CI 0.56–0.78; P < 0.0001; I2 = 69%) but at higher risk of stent thrombosis (RR 1.59, 95% CI 1.01–2.50; P = 0.04; I2 = 0%).

 

NIHR Signal: Significant risk of another thrombosis remains if anticoagulation is stopped

NIHR Dissemination Centre

This expert commentary of a meta-analysis (18 studies, n= 7,515) states clinical decisions to cease anticoagulation should remain tailored to each patient's circumstances and balanced against risk of bleeding.

 

Pharmacovigilance Risk Assessment Committee (PRAC) recommends Xeljanz (tofacitinib) be used with caution for all patients at high risk of blood clots

European Medicines Agency

PRAC has concluded that tofacitinib could increase risk of blood clots in the lungs and deep veins in patients who are already at high risk. Also, patients older than 65 years of age should be treated with tofacitinib only when there is no alternative treatment.

 

 

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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Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial

Annals of Internal Medicine

In this RCT of 190 APS patients, after 3years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76] prespecified noninferiority margin for RR was 1.40).

 

Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial

The Lancet

RCT of 9202 patients treated within 3hrs of injury reports lower risk of head injury-related death at 28days with tranexamic acid (18.5%) vs placebo (19.8%; RR 0.94 [95% CI 0.86–1.02]), and this was statistically significant in those with mild-moderate injury (RR 0.78, 0.64–0.95).

 

US FDA approves rivaroxaban (Xarelto) for the prevention of venous thromboembolism in acute medical patients

Biospace Inc.

Approval is based on data from the phase III MAGELLAN and MARINER trials. MAGELLAN met its co-primary endpoints, demonstrating non-inferiority to enoxaparin in short-term (10 days) and superiority in long-term (35 days) use, while MARINER demonstrated reduction in symptomatic VTE.

 

 

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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NIHR Signal: Short-term dual antiplatelet treatment may be best for most patients after receiving a drug-eluting stent

National Institute for Health Research

Expert commentary is provided on a network meta-analysis (17 RCTs, n= 46,864) which showed standard 12-month treatment increased the risk of any bleeding compared with 6 month short-term treatment (OR 1.39, 95% CI 1.01 to 1.92).

 

Adherence and persistence to direct oral anticoagulants in atrial fibrillation: a population-based study

Heart

Study (n=36,652) found adherence & persistence to direct oral anticoagulants are low at 1 yr with heterogeneity across drugs and over time at individual and system levels. Authors state better understanding of contributory factors will inform interventions to improve adherence.

 

Antithrombotic treatment after coronary artery bypass graft surgery: systematic review and network meta-analysis

British Medical Journal

Analysis (20 RCTs;n=4083) found moderate evidence to support dual antiplatelet use [aspirin(AS)+ticagrelor; OR 0.50,95% CI 0.31-0.79, NNT 10 or AS+clopidogrel; 0.60;0.42-0.86, 19] to reduce saphenous vein graft failure vs aspirin, with no significant differences in major bleeding.

 

Comparison of Events Across Bleeding Scales in the ENGAGE AF-TIMI 48 Trial

Circulation

In this study of edoxaban vs warfarin (n=21,105; and 10,311 total bleeding events), there was ~4-fold difference in frequency of most severe bleeding events across commonly used bleeding scales (ISTH, TIMI, GUSTO, and BARC) among patients with AF at risk for stroke.

 

Long-term Thromboembolic Risk in Patients With Postoperative Atrial Fibrillation After Left-Sided Heart Valve Surgery

JAMA Cardiology

Study found new-onset post op AF (POAF) was linked to a similar long-term risk of thromboembolism as nonvalvular AF (crude incidence rates 21.9 and 17.7 events/1000 person-years respectively), highlighting need for further studies addressing anticoagulation in POAF population.

 

Revised SPC: Plavix (clopidogrel) tablets

electronic Medicines compendium

SPC now details that co-administration of opioids has the potential to delay and reduce the absorption of clopidogrel due to delayed gastric emptying. The use of parenteral antiplatelet agent in ACS should be considered where opioid co-administration is required.

 

Direct oral anticoagulant for the prevention of thrombosis in ambulatory patients with cancer: A systematic review and meta-analysis

Journal of Thrombosis and Haemastasis

Review of 28 studies reports that low‐dose direct oral anticoagulant prophylaxis reduces the rate of overall venous thromboembolism in high‐risk cancer patients starting systemic chemotherapy but may increase the risk of 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:

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Association of General Anesthesia vs Procedural Sedation With Functional Outcome Among Patients With Acute Ischemic Stroke Undergoing Thrombectomy: A Systematic Review and Meta-analysis

Journal of the American Medical Association

Review of 3 RCTs (n=368) found that protocol-based general anaesthesia was associated with less disability at 3 months vs procedural sedation (difference = +0.43 on modified Rankin Scale score, OR 1.58, 95% CI 1.09-2.29).

 

Compression stockings to prevent post-thrombotic syndrome in adults, a Bayesian meta-analysis

Thrombosis Reasearch

Review of 4 studies found that compression stockings reduced post thrombotic syndrome (PTS) vs. control in acute DVT, but that the difference was not statistically significant (OR = 0.57, 95% CI: 0.21-1.20).

 

Very Short Dual Antiplatelet Therapy after Drug-eluting Stent Implantation in Patients with High Bleeding Risk: Insight from the STOPDAPT-2 Trial

Circulation

Japanese RCT (n=3,009) found 1-month therapy reduced major bleeding vs. 12-months (0.41% vs. 2.71%, HR 0.15, 95% CI 0.03-0.65, p=0.01); without any increase in CV events (3.48% vs. 5.98%, absolute difference -2.50%, 95% CI -5.06% to 0.06%, HR 0.57, 95% CI 0.32-1.03, p=0.06).

 

 


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-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Asians With Atrial Fibrillation

Stroke

Review, based on subanalyses of 5 RCTs and 21 observational cohorts, found use of NOACs is noninferior vs warfarin with respect to risk of stroke or systemic embolism, all-cause mortality, major bleeding and intracranial bleeding, irrespective of the NOAC type and dose.

 

Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK

BMJ Open

Database study (n=30 467; 2011-2016) reported 76.9% of patients starting NOACs were prescribed an appropriate dose. Underdosing more frequent in apixaban vs dabigatran and rivaroxaban cohorts. Overdosing more frequent in dabigatran vs rivaroxaban or apixaban cohorts.

 

Rivaroxaban versus warfarin treatment among morbidly obese patients with venous thromboembolism: Comparative effectiveness, safety, and costs

Thrombosis Reasearch

Retrospective US study of 2890 matched pairs of morbidly obese VTE patients reported similar recurrent VTE risk (OR: 0.99; 95% CI: 0.85–1.14) and major bleeding (0.75: 0.47–1.19) with rivaroxaban vs warfarin. Hospitalizations and outpatient visits were lower with rivaroxaban.

 

Oral Anticoagulation in patients with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1

European Heart Journal

This report outlines the currently available evidence in this field and provides a risk stratification of the individual thromboembolic risk in patients with AF and a CHA2DS2-VASc score of 1 to guide clinicians on whether to anticoagulate or not.

 

Revised SPC: Brilique (ticagrelor) film coated tablets – all strengths

electronic Medicines compendium

The SPC has been updated to warn of potential for ticagrelor to interfere with platelet function tests to diagnose heparin induced thrombocytopenia (HIT).

 

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

Cochrane Database of Systematic Reviews

Updated review of 7 RCTs (n=1728) concludes prolonged thromboprophylaxis (14 days) with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality.

 

Medical Management vs Mechanical Thrombectomy for Mild Strokes An International Multicenter Study and Systematic Review and Meta-analysis

JAMA Neurology

Pooled analysis of data from 251 patients with mild-deficit emergency large-vessel occlusion stroke concludes mechanical thrombectomy has a similar efficacy and safety profile vs best medical management, and a separate systematic review confirms this finding.

 

Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or with Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights from the AUGUSTUS Trial

Circulation

Study (n=4,614) shows regimen of apixaban + P2Y12 inhibitor without aspirin provides superior safety & similar efficacy in atrial fibrillation patients who have ACS (managed medically or with PCI), or those undergoing elective PCI; vs. regimens with VKAs, aspirin, or both.

 

Female sex as a risk factor for ischaemic stroke varies with age in patients with atrial fibrillation

Heart

Study (n=159,222) found the female/male ischaemic stroke risk ratio varied with age. Only women aged >75 years had a higher risk, whereas women aged <65 years had a lower risk vs. men. Authors state findings challenge the 'sex category' of the CHA2DS2-VASc score.

 

Ticagrelor with or without Aspirin in High-Risk Patients after PCI

New England Journal of Medicine

RCT (n=7,119) found ticagrelor monotherapy was associated with lower incidence of clinically relevant bleeding vs. ticagrelor + aspirin (1.0% vs. 2.0%; HR 0.49; 95% CI, 0.33 to 0.74), with no higher risk of death, myocardial infarction, or stroke.

 

 

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 thromboembolism prevention in atrial fibrillation

Heart

Review discusses this association, medical/non-medical therapy for stroke prevention, guideline recommendations for prevention, electrical and pharmacological cardioversion, ablation therapy and antithrombotic medication management, as well as key outstanding research questions.

 

Personalized Prediction of Cardiovascular Benefits and Bleeding Harms From Aspirin for Primary Prevention: A Benefit–Harm Analysis

Annals of Internal Medicine

This study, based on an analysis of 245,028 persons (43.6% women) aged 30-79yrs without established CVD who had their CVD risk assessed suggests a model that provides a personalised prediction of the benefits and bleeding harms from aspirin when used for primary prevention of CVD.

 

Head injury: assessment and early management – updated guideline [CG176]

National Institute for Health and Care Excellence

Updates have been made to the recommendations on head CT scans in people on anticoagulant treatment, diagnosis and management of post head injury hypopituitarism, and management of indirect brain injuries.

 

 

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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Bleeding and New Cancer Diagnosis in Patients with Atherosclerosis

Circulation

Study (n=27,395) found that in patients with atherosclerosis treated with antithrombotic drugs, any GI bleeding was linked to new GI cancer diagnosis (HR 20.6, 95% CI, 15.2 to 27.8); likewise for genitourinary(GU) bleeding and new GU cancer diagnosis (32.5; 24.7 to 42.9).

 

Rivaroxaban versus Aspirin in Prevention of Venous Thromboembolism: A Meta-Analysis of 9 Randomized Controlled Trials comprising 7,656 Patients

Thrombosis and Haemostasis

Review of 9 RCTs (n=7,656) found that rivaroxaban reduced VTE vs aspirin (1.3% vs 3.5%, RR 0.36, 95% CI 0.26-0.48), but increased non-major bleeding (11.5% vs 7.5%, 1.28, 1.13-1.44). There was no difference in all-cause mortality and major bleeding.

 

Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries

Annals of Internal Medicine

Meta-analysis of registry data from 5 countries concludes prevalence of hemophilia is higher than previously estimated: prevalence (per 100,000 males) is 17.1 cases for all severities of haemophilia A, and 3.8 cases for all severities of haemophilia B.

 

 

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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Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis: A Randomized Clinical Trial

JAMA Neurology

RCT (n=120) found no recurrent VTEs and one major bleeding event with dabigatran and two with warfarin. Authors conclude that both may be effective for recurrent VTE prevention in patients with central venous thrombosis.

 

Effect of Low-Intensity vs Standard-Intensity Warfarin Prophylaxis on Venous Thromboembolism or Death Among Patients Undergoing Hip or Knee Arthroplasty: A Randomized Clinical Trial

Journal of the American Medical Association

RCT (n=1,650) failed to establish non-inferiority of an INR goal of 1.8 vs 2.5 for VTE prevention post hip or knee arthroplasty (rate of VTE or death was 5.1% for INR target of 1.8 vs 3.8% for INR target 2.5, difference 1.3%, p=0.06 for non-inferiority).

 

A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI

New England Journal of Medicine

Open label RCT (n=2,488) found a similar efficacy outcome (composite of stent thrombosis, mortality and myocardial infarction) for a CYP2C19 genotype–guided strategy vs standard ticagrelor or prasugrel, but minor bleeding rates were lower (9.8% vs 12.5% p=0.04).

 

Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial

The Lancet

RCT (n=1,506) found that edoxaban was non-inferior to a vitamin K antagonist (VKA) for bleeding events (annualised rate of 20.7% for edoxaban vs 25.6% for VKAs, HR 0.83, 95% CI 0.65-1.05, non-inferiority margin HR = 1.20, p=0.001 for non-inferiority).

 

Biosimilars of low molecular weight heparins: Relevant background information for your drug formulary

British Journal of Clinical Pharmacology

This review gives background information on critical factors for the formulary uptake process of LMWHs. It introduces a straightforward instrument to enhance formulary policy making in a transparent, rational way (the System of Objectified Judgment Analysis/Infomatrix model).

 

2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer

The Lancet Oncology

This guidance is based on a systematic review of the literature. Results from head to head trials comparing DOACs with LMWHs are included for information in the guidance along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

 

Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease

New England Journal of Medicine

Study of 2236 AF patients reports rivaroxaban monotherapy is non-inferior to combination therapy with antiplatelet+rivaroxaban for the primary efficacy end point (composite of stroke, systemic embolism, MI, unstable angina requiring revascularization, or death from any cause).

 

Estimating individual lifetime benefit and bleeding risk of adding rivaroxaban to aspirin for patients with stable cardiovascular disease: results from the COMPASS trial

European Heart Journal

Predicted individual gain in life expectancy free of stroke or MI from added low-dose rivaroxaban had a median of 16 months (range 1–48 months), while predicted individualized lifetime lost in terms of major bleeding had a median of 2 months (range 0–20 months).

 

Ticagrelor in Patients with Stable Coronary Disease and Diabetes

New England Journal of Medicine

RCT (n=19,220; median follow-up 39.9 months) reported lower incidence of ischaemic cardiovascular events with ticagrelor + aspirin vs aspirin (7.7 vs. 8.5%; HR, 0.90; 95% CI, 0.81 to 0.99; P=0.04) but higher incidence of major bleeding (2.2 vs. 1.0%; 2.32; 1.82 to 2.94; P<0.001).

 

Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes

New England Journal of Medicine

Open-label RCT (n=4018) reported incidence of death, MI, or stroke was significantly lower in the prasugrel group vs ticagrelor group (6.9% vs 9.3%; HR, 1.36; 95% CI, 1.09 to 1.70; P=0.006) with no difference in major bleeding (4.8% vs 5.4%; 1.12; 0.83 to 1.51; P=0.46).

 

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

The Lancet

Sub-group analysis (n=11,154) reported that addition of ticagrelor to aspirin reduced cardiovascular death, MI, and stroke vs placebo for a median of 3.3 years (7.3 vs 8.6% in the PCI group; HR 0.85; 95% CI 0.74–0.97; p=0.013), although with increased risk of major bleeding.

 

2019 European Society of Cardiology Guidelines for the diagnosis and management of acute pulmonary embolism

European Heart Journal

These guidelines, an update of the 2014 guidelines, outline the optimal diagnosis, assessment, and treatment of patients with 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

 

 

Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin

Gastroenterology

RCT (n=17,598 followed up for median 3.01 years, with 53,152 patient-years of follow-up) found no statistically significant difference between pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% placebo group; OR 1.33; 95% CI, 1.01–1.75).

 

Increasing number of patients prescribed risky anticoagulant drug combinations

Pharmaceutical Journal

Statistics from the Medication Safety Dashboard show that between Sept 18 and Nov 18, there were more than 14,000 patients in England prescribed an NSAID with an anticoagulant and more than 30,000 patients prescribed an antiplatelet and anticoagulant without gastro-protection.

 

 

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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