Anticoagulation news items. Week commencing 3rd August 2020
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.
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:
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Anticoagulation news items. Week commencing 27th July 2020
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:
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Anticoagulation news items. Week commencing 20th July 2020
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.
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.
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.
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:
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Anticoagulation news items. Week commencing 13th July 2020
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.
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.
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:
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Anticoagulation news items. Week commencing 6th July 2020
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.
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.
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:
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Anticoagulation news items. Week commencing 29th June 2020
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.
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]).
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).
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.
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).
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Anticoagulation news items. Week commencing 22nd June 2020
National Institute for Health and Care Excellence
Avatrombopag is recommended as an option for treating severe thrombocytopenia (platelet count of <50,000/microlitre of blood) in adults with chronic liver disease having a planned invasive procedure.
Community pharmacy-based study of adherence to non-vitamin K antagonist oral anticoagulants
Heart
Belgian study (n=766) found a positive patient attitude towards DOAC therapy, with 21% reporting non-adherence according to the Medication Adherence Report Scale, and unintentional non-adherence being the most commonly reported reason (15.4%).
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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Anticoagulation news items. Week commencing 15th June 2020
Piperacillin/tazobactam-induced coagulopathy in a patient through a vitamin K-dependent mechanism
European Journal of Hospital Pharmacy
Case report describes 70-year-old female patient whose INR increased following piperacillin/tazobactam (PTZ). Coagulopathy was reversed with vitamin K, suggesting PTZ can induce coagulopathy through a vitamin K-dependent mechanism.
DTB Select: DOAC dose adjustment in renal impairment
Drug and Therapeutics Bulletin
Commentary and context are provided for a US registry-based study (n=6,682) which found that of the 4% of people treated with a DOAC who met the criteria for a dose reduction, only 20% of them had an appropriate dose adjustment.
Journal of the American Medical Association
RCT (n=3056) found composite endpoint of major bleeding and CV and cerebrovascular events was less frequent with ticagrelor monotherapy vs dual therapy with aspirin (3.9% vs 5.9%, HR 0.66, p=0.01) but lower than expected event rates should be considered when interpreting results.
The Lancet
This RCT in adults with severe GI bleeding (n=12,009) found no difference between tranexamic acid and placebo in death due to bleeding within 5 days (4% v 4%; RR 0.99; 95% CI 0.82-1.18) with a higher risk of VTE events (1.85; 95% CI 1.15-2.98) and seizures (1.73; 1.03-2.93).
Circulation
Meta-analysis of 5 RCTs (n=32,145) found discontinuation of aspirin therapy 1-3 months post PCI reduced major bleeding risk vs continued dual antiplatelet therapy (1.97% vs 3.13%; HR 0.60, 95% CI 0.45-0.79), with no observed increase in MACE (2.73% vs 3.11%; HR 0.88, 0.77-1.02).
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Anticoagulation news items. Week commencing 8th June 2020
JAMA Internal Medicine
Study (n=24,943) found concurrent use of clarithromycin compared with azithromycin was associated with a small, significantly greater 30-day risk of hospital admission with major haemorrhage (adjusted hazard ratio, 1.71 [95% CI, 1.20-2.45]; absolute risk difference, 0.34%).
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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Anticoagulation news items. Week commencing 1st June 2020
Circulation
Ticagrelor reduced CV and all-cause mortality (HR 0.82 and 0.83, respectively) whereas there was no significant mortality reduction with prasugrel vs clopidogrel (0.90 and 0.92, respectively). Both prasugrel and ticagrelor increased major bleeding vs clopidogrel (1.26 and 1.27).
British Journal of Clinical Pharmacology
Prospective study (n=1717) found clopidogrel-treated patients had a higher annual rate of cardiovascular mortality, major adverse cardiovascular event and all‐cause mortality (all P< 0.001) without differences in major bleeding (P = 0.587) vs novel oral P2Y12 inhibitors.
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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