Items filtered by date: September 2020

EU review extended for marketing authorisation application for haemophilia A gene therapy Valrox (valoctocogene roxaparvove)

PharmaTimes
The company disclosed in a US Securities and Exchange Commission filing that European Medicines Agency has asked for full 52-week results from 134 patients taking part in ongoing phase III study and potential submission of data is anticiparted by end of first quarter of 2021.

 

Treatment of distal deep vein thrombosis

Cochrane Database of Systematic Reviews
Review of 8 RCTs (n=1,239) found evidence of benefit for anticoagulation therapy using vitamin K antagonists with little or no difference in major bleeding events although there was an increase in clinically relevant non‐major bleeding vs no intervention or placebo.

 

Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury

Journal of the American Medical Association
RCT (n=1,063) found that, among patients with moderate to severe traumatic brain injury, out-of-hospital tranexamic acid administration within 2 hours of injury vs placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale.

 

Andexanet alfa (Ondexxya®) accepted for use within NHS Scotland on interim basis subject to ongoing evaluation and future reassessment

Scottish Medicines Consortium
Andexanet alfa intravenous infusion is approved for adult patients treated with a direct factor Xa inhibitor (apixaban or rivaroxaban) when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

 

Low molecular weight heparin for prevention of microvascular occlusion in digital replantation

Cochrane Database of Systematic Reviews
In this updated review (4 RCTs, n=258) low to very low‐certainty evidence showed no benefit from low molecular weight compared to unfractionated heparin on success rates of replantation or affect microvascular insufficiency due to vessel occlusion.

 

Andexanet alfa for reversing anticoagulation from apixaban or rivaroxaban – second appraisal consultation

National Institute for Health and Care Excellence
In DRAFT guidance, NICE recommends andexanet alfa as an option for reversing anticoagulation from apixaban or rivaroxaban in adults with life-threatening or uncontrolled bleeding, only if the bleed is in the GI tract and it is provided according to the commercial arrangement.

 

 

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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Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series

Annals of Internal Medicine
Study notes COVID-19 mainly involves lungs, causing diffuse alveolar damage and acute respiratory insufficiency. Autopsy findings (n=10) found death may be caused by thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite prophylactic anticoagulation.

 

The Effect of Adding Ticagrelor to Standard Aspirin on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting (POPular CABG): A Randomized, Double-Blind, Placebo-Controlled Trial

Circulation
In RCT (n=499≥1 saphenous vein graft [SVGs]), addition of ticagrelor to standard aspirin did not reduce SVG occlusion at one year after CABG (occlusion rate, ticagrelor group 10.5% vs. 9.1% placebo group; OR 1.29; 95% CI: 0.73 -2.30; p=0.38).

 

Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation

New England Journal of Medicine
RCT (n=665) found incidence of bleeding (15.1% vs. 26.6%; risk ratio, 0.57; 95% CI, 0.42-0.77; p=0.001) and composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin compared to aspirin plus clopidogrel administered for 3 months.

 

Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation

New England Journal of Medicine
RCT in 984 Japanese patients (aged ≥80 years) found once-daily 15mg dose of edoxaban superior to placebo in preventing stroke/systemic embolism (event rate 2.3% vs. 6.7%; HR 0.34; 95% CI 0.19 to 0.61;p<0.001), and did not result in significantly higher incidence of major bleeding.

 

Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial

The Lancet
RCT (n=2338; South Korea) found prasugrel-based dose de-escalation strategy from 1 month after PCI reduced risk of net adverse clinical outcomes (HR 0.70; 95% CI,0.52–0.92), up to 1 year, mainly driven by reduction in bleeding (0.48; 0.32–0.73), without increase in ischaemia.

 

2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

European Heart Journal
Guidance covers diagnosis, risk assessment and outcomes, pharmacological & invasive treatments, MI with non-obstructive coronary arteries and alternative diagnoses, special populations, long-term management, quality measures, management strategy, key messages and gaps in evidence.

 

Comparison Between Ticagrelor and Clopidogrel in Elderly Patients with an Acute Coronary Syndrome: Insights from the SWEDEHEART Registry

Circulation
Secondary analysis of a study (n=14,005) found that, in those ≥80 years, the incidence of the primary ischaemic outcome was similar for ticagrelor and clopidogrel, but ticagrelor was associated with a 17% and 48% higher risk of death & bleeding, respectively.

 

Edoxaban in atrial fibrillation patients with percutaneous coronary intervention by acute or chronic coronary syndrome presentation: a pre-specified analysis of the ENTRUST-AF PCI trial

European Heart Journal
Analysis of the ENTRUST-AF PCI trial (n=1,506) found the difference in primary bleeding endpoint between edoxaban with P2Y12 inhibitor vs vitamin K antagonist with aspirin and P2Y12 inhibitor was nonsignificant, and consistent between acute and chronic coronary syndrome cohorts.

 

 

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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Perioperative oral eltrombopag versus intravenous immunoglobulin in patients with immune thrombocytopenia: a non-inferiority, multicentre, randomised trial

The Lancet Haematology

In this Canadian RCT (n=74) eltrombopag was non-inferior to IV immunoglobulin; with perioperative platelet targets achieved in 79% on eltrombopag and 61% on IV immunoglobulin (absolute risk difference 17.8%, p for non-inferiority=0.005). Eltrombopag was linked to 1 case of PE.

 

Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy

Cochrane Database of Systematic Reviews
Current evidence (34 RCTs; n=1960) does not support overall superiority of any anticoagulant. Compared to unfractionated heparin, citrate probably reduces major bleeding and probably has little or no effect on preventing clotting or death at 28 days. Further studies are required.

 

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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Management of Acute Pulmonary Embolism

Journal of the American Medical Association

This guidelines synopsis focuses on 2019 guidance from the European Society of Cardiology on diagnosis and management of acute pulmonary embolism, a common and potentially fatal disease with an estimated incidence of 0.7 to 1.4 per 1000 person-years.

Venous Thromboembolism Risk Assessment in Psychiatric Inpatients Audit

Sussex Partnership NHS Foundation Trust
The aim of this audit was to assess the use of VTE risk assessments and management of high-risk groups of psychiatric inpatients, and identify and implement ways in which VTE risk assessment can be carried out more systematically.

 

 

 

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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Dual Antiplatelet Therapy After Percutaneous Coronary Intervention and Drug-Eluting Stents: A Systematic Review and Network Meta-Analysis

Circulation
Review (24 RCTs, n=79,073) found short-term (<6-month) dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor (e.g. clopidogrel) monotherapy reduces major bleeding, while extended-term (>12-month), reduces myocardial infarction at the expense of more bleeding events.

 

Non‐vitamin K antagonist oral anticoagulants (NOACs) post‐percutaneous coronary intervention: a network meta‐analysis

Cochrane Database of Systematic Reviews
Review (5 RCTs, n=8,373) found no meaningful difference in efficacy outcomes between NOAC and vitamin K antagonists following percutaneous coronary interventions in people with non‐valvular atrial fibrillation; but NOACs may reduce risk of hospitalisation for adverse events.

 

Pulmonary embolism: update on management and controversies

British Medical Journal

Review covers epidemiology, diagnosis, PE in pregnancy and cancer, thrombophilia testing, antiphospholipid syndrome, recurrent PE, risk assessment, outpatient versus inpatient management, choice of anticoagulation treatment, long term effects of PE and emerging treatments.

 

 

 

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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Mortality risk associated with venous thromboembolism: a systematic review and Bayesian meta-analysis

The Lancet Haematology
In review of 86 RCTs, 52 of them, with data from >70 000 patients, were positive, with significantly increased VTE risk in patients in control vs. treatment groups (RR 2·74; 95% CrI 2·32–3·31,p<0·0001). Meta-analysis found causal effect of VTE prevention on mortality was null.

 

Management of anticoagulant-refractory thrombotic antiphospholipid syndrome

The Lancet Haematology
In this Viewpoint, authors discuss management, including general strategies to minimise thrombotic risk, intensification of anticoagulation, addition of antiplatelet agent, adjunctive treatment for thrombosis, immunomodulatory therapy, complement inhibition, and vascular options.

 

Alteplase for Acute Ischemic Stroke in Patients Aged >80 Years

Stroke
Pooled analyses of individual patient data from 7 RCTs of alteplase (n=6035) and registry studies support a positive benefit–risk profile of alteplase for acute ischaemic stroke, in patients aged >80 years, when administered according to other European regulatory criteria.

 

 

 

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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DTB select: MHRA DOAC safety reminder

Drug and Therapeutics Bulletin
It is noted that there has been a considerable increase in use of DOACs and a move to switch to them from warfarin during coronavirus pandemic due to less onerous monitoring, but it is stressed regular monitoring of renal function and appropriate dose adjustment still needed.

 

Age- and Weight-Adapted Dose of Prasugrel Versus Standard Dose of Ticagrelor in Patients With Acute Coronary Syndromes

Annals of Internal Medicine
Subgroup analysis (n=3997) found that in elderly or low-weight patients with ACS, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischaemic efficacy while protecting these patients against the excess risk for bleeding.

 

Assessment of Shared Decision-making for Stroke Prevention in Patients With Atrial Fibrillation: A Randomized Clinical Trial

JAMA Internal Medicine
RCT (n=922 pts,244 clinicians) found shared decision-making (SDM) encounter tool (individualised risk estimates & compares anticoagulant treatment options across issues of importance to patients) improved several measures of SDM quality and clinician satisfaction vs standard care.

 

Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System

Journal of the American Medical Association
Among 3334 patients, a thrombotic event occurred in 16.0% and was independently associated with mortality (HR 1.82; 95% CI, 1.54-2.15; P < .001). D-dimer level at presentation was independently associated with thrombotic events, consistent with an early coagulopathy.

 

Efficacy and safety of clopidogrel versus prasugrel and ticagrelor for coronary artery disease treatment in patients with CYP2C19 LoF alleles: a systemic review and meta‐analysis

British Journal of Clinical Pharmacology
Review of 12 studies (5,829 patients with CYP2C19 loss‐of‐function alleles) found those given ticagrelor or prasugrel had a lower risk of MACE (RR=0.52), CV death (0.41), all cause death (0.44) and stent thrombosis (0.55) than those who received clopidogrel (all p<0.05).

 

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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Pulmonary embolism in COVID-19 patients: a French multicentre cohort study

European Heart Journal
Study (n=1,240) identified independent risk factors linked to occurrence of PE in COVID-19 patients, including clinical and biological variables at admission, but these do not include traditional thrombo-embolic risk factors, highlighting major role of inflammation & coagulopathy.

 

Association of Factor V Leiden with Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data

Circulation
Analysis of 20 studies (61,147 patients; 6849 events) found Factor V Leiden (FVL) was not linked to increased risk of subsequent atherothrombotic events and mortality in high-risk patients with established and treated CHD, thus not supporting routine assessment of FVL status.

 

Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA

New England Journal of Medicine
RCT (n=11,016) found composite of stroke or death within 30 days was lower with ticagrelor–aspirin vs. aspirin alone (5.5. vs. 6.6%;HR 0.83; 95% CI, 0.71-0.96; p=0.02) but incidence of disability did not differ significantly and severe bleeding was more frequent with ticagrelor.

 

Acute Ischemic Stroke

New England Journal of Medicine
Review covers initial evaluation and imaging, use of alteplase within and after 4.5 hours of stroke onset, mechanical thrombectomy within and after 6 hours of stoke onset, tenecteplase, antithrombotic agents, and general medical & supportive care.

 

Atrial fibrillation and the prothrombotic state: revisiting Virchow’s triad in 2020

Heart
This review concludes that the mechanisms contributing to a pro-thrombotic state in AF fulfils Virchow's triad, and that improved understanding of the various factors involved in thrombus formation will allow better clinical risk stratification and targeted therapies in AF.

 

 

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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Warfarin and food, herbal or dietary supplement interactions: A systematic review

British Journal of Clinical Pharmacology
Review concluded that healthcare staff should be aware of increased risk of bleeding when following are taken with warfarin: Chinese wolfberry, chamomile tea, cannabis, cranberry, chitosan, green tea, Ginkgo biloba , ginger, spinach, St. John's Wort, sushi and smoking tobacco.

 

Association Between Treatment With Apixaban, Dabigatran, Rivaroxaban, or Warfarin and Risk for Osteoporotic Fractures Among Patients With Atrial Fibrillation

Annals of Internal Medicine
Population-based cohort study (n=23,515, Hong Kong) reports among AF patients, DOAC use may result in lower risk for osteoporotic fracture vs. warfarin at 24-month follow-up, and risk does not seem to be altered by choice of DOAC. Findings may be limited by residual confounding.

 

Revised SPC: Octaplex 1000 IU powder and solvent for solution for injection

electronic Medicines compendium
SPC updated with information on traceability and sodium content, and to note that no data are available regarding its use in the paediatric population. Sections 6.5 and 6.6 contain information on a new Nextaro® device.

 

Revised SPC: Sustanon (testosterone) 250, 250mg/ml solution for injection

electronic Medicines compendium

SPC now notes testosterone should be used with caution in patients with thrombophilia or risk factors for venous thromboembolism, as there have been studies/reports of thrombotic events even under anticoagulation treatment. 'Weight increased' has been added as an adverse effect.

 

Ticagrelor granted FDA Priority Review for secondary prevention of acute ischaemic stroke or transient ischaemic attack

Biospace Inc.
The accepted supplemental new drug application is based on results from the Phase III THALES trial, in which the combination of ticagrelor and aspirin was associated with a reduction in the primary composite endpoint of stroke and death compared to aspirin alone.

 

 

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 and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy

European Journal of Hospital Pharmacy

Retrospective study (n=145) reported that INR target was reached in 102 patients, aPTT ratio target was reached in 113 patients, and 79 of 106 patients reversed for bleeding achieved haemostatic effectiveness after four-factor prothrombin complex concentrate (all p<0.0001).

 

Patterns of oral anticoagulation use with cardioversion in clinical practice

Heart
Analysis of AF registry data (n=13 004; 1613 met criteria) reported no differences in death (HR 1.19, 95% CI 0.62 -2.28, p=0.61), stroke/TIA (1.18; 0.30 -4.74; p=0.81) or major bleeding (1.29; 0.66 -2.52; p=0.45) at 1 year in patients treated with DOAC vs vitamin K antagonist.

 

Revised SPC: Tygacil (tigecycline) 50mg powder for solution for infusion

electronic Medicines compendium
Recommendation has been added regarding the need for monitoring of coagulation parameters, including blood fibrinogen, prior to and during tigecycline treatment; as well as a related update to frequency of existing side effect hypofibrinogenaemia from not known to rare.

 

Direct-acting oral anticoagulants (DOACs): reminder of bleeding risk, including availability of reversal agents

Medicines and Healthcare products Regulatory Agency
Alert advises on need to remain vigilant, especially in patients with increased bleeding risks; and that specific reversal agents are available for dabigatran (Praxbind, [idarucizumab]), apixaban and rivaroxaban (Ondexxya [andexanet alfa]).

 

Cangrelor, Tirofiban and Chewed or Standard Prasugrel Regimens in Patients with ST-Segment Elevation Myocardial Infarction: Primary Results of the FABOLUS FASTER Trial

Circulation
RCT (n=122) reports cangrelor provided inferior inhibition of platelet aggregation (IPA) vs. tirofiban; both treatments yielded greater IPA vs. chewed prasugrel (which led to higher active metabolite concentration but not greater IPA compared with standard prasugrel tablet).

 

New product Inhixa (enoxaparin sodium) 30,000 IU (300 mg)/3 mL solution for injection in multidose vial

electronic Medicines compendium
This is new presentation, licensed for VTE treatment and medical and surgical prophylaxis, ACS, treatment of unstable angina & non ST-segment elevation myocardial infarction (NSTEMI), STEMI, and prevention of thrombus formation in extra corporeal circulation during haemodialysis.

 

Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study

The Lancet Haematology
Study (n=68) found coagulation activation is common in hospitalised patients with COVID-19, with elevated plasma von Willebrand factor levels increasing with disease severity. Findings identify a potential prognostic role for measurement of endothelial markers in this setting.

 

Revised SPCs: Pradaxa (dabigatran) hard capsules

electronic Medicines compendium
SPC updated to add 'neutropenia' and 'agranulocytosis' as adverse reactions (frequency not known).

 

 

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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