Anticoagulation news items. Week commencing 21st January 2019
Journal of the American Medical Association
Review of 13 RCTs (n=164,225) found that aspirin use reduced a composite of CV mortality, non-fatal MI/stroke vs no aspirin (57.1 vs 61.4 /10,000 patient-years, HR 0.89, 95% CI 0.84-0.95, NNT 265), however aspirin had an increased risk of major bleeding (1.43, 1.30-1.56, NNH 210).
Circulation
RCT (n=27,395) found a reduced risk of strokes with rivaroxaban 2.5mg twice daily plus aspirin 100mg daily vs aspirin alone (0.9% per year vs 1.6% per year, HR 0.58, 95% CI 0.44-0.76). The effect of the combination compared with aspirin was consistent across subgroups.
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Anticoagulation news items. Week commencing 14th January 2019
Revised SPCs: Efient (prasugrel) 5 mg 10 mg film-coated tablets
electronic Medicines compendium
SPCs have been updated to advise a delayed and decreased exposure to oral P2Y12 inhibitors, including prasugrel and active metabolite, has been observed in patients with ACS treated with morphine. This interaction may be related to reduced GI motility and apply to other opioids.
British Journal of Clinical Pharmacology
Authors of this narrative review reflect that HIV infection increases the risk of stroke. Choosing antiretrovirals with the lowest drug–drug interaction and with lower impact on the cardiovascular system, and the use of DOACs may help reduce the risk of stroke in this group.
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Anticoagulation news items. Week commencing 7th January 2019
Thrombolytic therapy for pulmonary embolism
Cochrane Database of Systematic Reviews
Review of 18 RCTs (n=2197) concludes low‐quality evidence shows thrombolytics in addition to heparin reduce death and recurrence of pulmonary embolus following acute pulmonary embolism, compared with heparin alone. The included studies used a variety of thrombolytic drugs.
British Medical Journal
Analysis (n=80 396 matched to 391,494 controls.) found most oral preparations were linked to increased VTE risks. Conjugated equine oestrogens with or without medroxyprogesterone acetate, were linked to highest risks. No increased risk was found for transdermal preparations.
European Heart Journal
Review of data from the ENGAGE AF-TIMI 48 trial found that an increased BMI was independently associated with a lower risk of stroke or systemic embolic events (per 5 kg/m2 increase, HR=0.88, p=0.0001), but increased risk of major bleeding (HR 1.06, P = 0.025).
Inhaled Tranexamic Acid for Hemoptysis Treatment
Chest
RCT (n=47) found that resolution of hemoptysis within 5 days of admission was observed in more tranexamic acid (TXA) treated vs placebo (96% vs 50%; p< 0.0005). TXA patients also had a shorter hospital stay and required fewer interventional procedures.
Journal of the American Medical Association
RCT (n=195) was stopped early due to futility. Among patients with acute STEMI presenting within 6 hours of symptoms, adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction vs placebo.
Cochrane Database of Systematic Reviews
Review of 31 RCTs (n=2392) found that paucity of good‐quality evidence precludes the drawing of conclusions for clinical practice. Sample sizes of future RCTs would need to be greatly increased to detect a reduction in mortality or thromboembolic events between treatment arms.
Uterotonic agents for preventing postpartum haemorrhage: a network meta‐analysis
Cochrane Database of Systematic Reviews
Analysis (196 trials; n=135,559; 7 uterotonic agents) found all agents were generally effective vs. placebo or no treatment. Some oxytocin (OX) combination regimens may have some additional desirable effects vs current standard OX but are linked to significant side effects.
Tranexamic acid for patients with nasal haemorrhage (epistaxis)
Cochrane Database of Systematic Reviews
Review of 6 RCTs (n=692) found moderate‐quality evidence that there is probably a reduction in the risk of re‐bleeding with use of either oral or topical tranexamic acid in addition to usual care in adults with epistaxis, compared to placebo with usual care.
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Anticoagulation news items. Week commencing 24th and 31st December 2018
National Institute for Health Research Signal
Commentary is provided of trial which found continued use of rivaroxaban offered very small reduction in VTE risk, but also slightly increased risk of major bleeding (neither statistically significant). Trial was terminated because of lower than expected number of clots.
European Heart Journal
Data from phase 3 trials found that, irrespective of direct oral anticoagulant (DOAC) used, rates of stroke or systemic embolism and major bleeding were higher in those eligible for reduced-dose DOACs than in those eligible for full-dose DOACs (2.70% vs 1.60% and 4.35% vs 2.87%).
European Heart Journal
Open label RCT (n=326) found a higher intra-procedural heparin requirement with 24-hour skipped DOACs vs single dose skipped and uninterrupted regimens (p<0.001) though the incidence of major bleeding up to 1 month after ablation did not differ.
JAMA Internal Medicine
Chinese cohort study (n=6,804) found that parenteral anticoagulant therapy did not reduce the incidence of in-hospital death, or rate of myocardial infarction vs those that did not receive it. Bleeding was more frequent with anticoagulation (2.5% vs 1.0%, p<0.001).
Human coagulation factor X for hereditary factor X deficiency (all ages)
NHS England
NHS England will not routinely commission human coagulation factor X for people of all ages with hereditary factor X deficiency who need long term prophylaxis owing to insufficient published evidence.
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Anticoagulation news items. Week commencing 17th December 2018
British Medical Journal
Review of 3 RCTs (n=10,447) found that compared with aspirin alone clopidogrel plus aspirin, started within 24 hours of symptom onset, reduced the risk of non-fatal recurrent stroke (RR 0.70, 95% CI 0.61-0.80, absolute risk reduction 1.9%).
Graduated compression stockings for prevention of deep vein thrombosis
Cochrane Database of Systematic Reviews
Review of data from 20 high-quality RCTs (n=1681) concludes graduated compression stockings are effective in reducing the risk of DVT in hospitalised patients who have undergone general and orthopaedic surgery, with or without other methods of background thromboprophylaxis.
Rutosides for treatment of post‐thrombotic syndrome
Cochrane Database of Systematic Reviews
Review of 3 low quality RCTs (n=233) concludes rutosides are not superior to placebo or elastic compression stockings for post‐thrombotic syndrome, characterised by pain, swelling, and skin changes in affected limb. Rutosides are a group of compounds derived from horse chestnut.
NIHR Signal: The best dose of aspirin for cardiovascular protection may depend on body weight
National Institute for Health Research Signal
Expert commentary is provided for a review of 13 RCTs which found that low dose aspirin was effective for secondary prevention in those <70kg, but not >70kg. The findings reinforce the importance of tailoring the aspirin dose to a patient's characteristics, including weight.
European Heart Journal
Analysis of 11 trials (n=157,248) found at mean follow-up of 6.6 years, aspirin was not linked to lower incidence of all-cause mortality but to increased incidence of major bleeding (RR 1.47, 95% CI 1.31–1.65; p< 0.0001) and intracranial haemorrhage (1.33, 1.13–1.58; p = 0.001).
Biospace Inc.
Application is based on data from phase 3 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.
British Journal of Clinical Pharmacology
French new-users cohort study (n=14,442) reported that dabigatran at either dose was associated with less major bleeding, stroke and systemic embolism and all-cause mortality than matched VKA-treated patients.
The Lancet
US database study (3091 apixaban users and 12,163 rivaroxaban users) reported that use of apixaban vs rivaroxaban was associated with decreased risk of recurrent VTE (HR 0.37; 95% CI 0.24–0.55]; p<0.0001) and major bleeding events (0.54; 0.37–0.82; p=0.0031).
MI risk associated with naproxen and diclofenac in spondyloarthritis: DTB Select summary
Drug and Therapeutics Bulletin
Summary and context is provided for analysis of the incidence of myocardial infarction in people with spondylarthritis and osteoarthritis treated with NSAIDs which provides further evidence that diclofenac is associated with a higher risk than naproxen.
British Journal of Clinical Pharmacology
Retrospective cohort study (n=14,577) found all DOACs were similarly effective in preventing stroke, systemic embolism or CV death, while patients on rivaroxaban showed highest bleeding risks.Observed differences in risks of all‐cause mortality, MI and PE warrant further research.
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Anticoagulation news items. Week commencing 10th December 2018
In use product safety assessment report for enoxaparin biosimilars (INHIXA and AROVI)
Specialist Pharmacy Service
This assessment on Inhixa and Arovi (enoxaparin biosimilars) describes the in-use medication safety considerations resultant from the products' presentation or other pre-defined characteristics. Potential next steps and mitigation actions are suggested.
Cyclin-Dependent Kinase Inhibitor–Associated Thromboembolism
JAMA Oncology
An overview of the evidence that this drug class (of which palbociclib is the first in class) is associated with an increased incidence of thromboembolism. NICE support the use of palbociclib for use within its marketing authorisation.
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 3rd December 2018
Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery
Cochrane Database of Systematic Reviews
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 after major abdominal or pelvic surgery.
Circulation
Study (n=272,315) found triple therapy linked to high rates of major bleeding vs. dual or monotherapy. Very high major bleeding rates occurred among patients on triple therapy aged > 90 years or with CHA2DS2-VASc > 6 or with a history of major bleeding.
Journal of the American Medical Association
Retrospective study found during 754,389 person-years of anticoagulation with apixaban, dabigatran, rivaroxaban [RV], and warfarin, risk of hospitalisation for upper GI bleeding was highest for RV. PPI cotherapy (264,447 person-years) was linked to lower overall GI bleeding risk.
Apixaban to Prevent Venous Thromboembolism in Patients with Cancer
New England Journal of Medicine
RCT (n=574) found apixaban (2.5mg BD) resulted in lower rate of venous thromboembolism vs. placebo in intermediate/high-risk ambulatory patients with cancer starting chemo (12 [4.2%] vs. 28 [10.2%]; HR 0.41; 95% CI, 0.26-0.65; p<0.001) but higher rates of major bleeding episodes.
Conference report: positive results for emicizumab for paediatric haemophilia A
Biospace Inc.
Primary analysis of the HAVEN 2 study (n=85) has found that once-weekly emicizumab dosing showed a 99% reduction in treated bleeds compared to prior treatment with bypassing agents.
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Anticoagulation news items. Week commencing 26th November 2018
Circulation
Registry study (n=52,014) found an elevated mortality rate in the first month after diagnosis vs the first year (6.8 vs 4.3 100 person years for first month and first year respectively). The elevated 1-month mortality rate was mostly attributable to cardiovascular mortality.
The Lancet Respiratory Medicine
RCT (N=105) reported an improvement from baseline in mean 6-min walk distance in the treprostinil high and low dose groups (44·98 m and 4·29 m; p=0·0016). Treprostinil is an investigational prostacyclin analogue that has received orphan drug status in the EU.
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Anticoagulation news items. Week commencing 19th November 2018
JAMA Cardiology
This review of 3 RCTs (n=3943) comparing bare-metal stents (BMSs) to drug-eluting stents (DESs) with shortened duration of dual antiplatelet therapy (one month only) found DES were associated with lower risk of major adverse cardiac events and other adverse outcomes.
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 12th November 2018
The role of plasminogen activators in stroke treatment: fibrinolysis and beyond
The Lancet Neurology
This review describes the pathophysiological effects of plasminogen activators and how, in the future, their non-fibrinolytic functions could be used for the treatment of patients with acute ischaemic and haemorrhagic stroke.
Practice guide to dosing of direct acting oral anticoagulants in patients with renal impairment
Specialist Pharmacy Service
This paper, focusing on use of DOACs in patients with atrial fibrillation, discusses the debate regarding the dosing of DOACs in patients with renal impairment and offers some practical advice on selecting the dose in the clinical setting.
Management of life threatening bleeds from arteriovenous fistulae and grafts
NHS Improvement
Alert signposts providers to resources produced jointly by British Renal Society and Vascular Access Society of Britain and Ireland to help staff, carers and patients recognise warning signs. Providers are asked to ensure local guidance incorporates advice in these resources.
Cochrane Database of Systematic Reviews
Review (4 trials, n=450) found no RCT evidence that percutaneous vascular interventions are superior to intravenous thrombolytic treatment with respect to functional outcome. Quality of evidence was low (outcome assessment was blinded but not treating physician/participants).
Circulation
Paper reports that ABC-stroke and ABC-bleeding risk scores which comprise clinical variables and CV biomarkers to estimate risk of stroke/systemic embolic events and bleeding, respectively, were well-calibrated and outperformed the CHA2DS2-VASc and HAS-BLED scores, respectively.
Self‐poisoning with 60 tablets of Apixaban, a pharmacokinetics case report
British Journal of Clinical Pharmacology
Apixaban was eliminated following first order elimination with a calculated half‐life of 10.8 h. Anti‐Xa activity seems to be linearly related to concentration up to 4000 μg/ l. This report suggests use of activated charcoal should be effective up to 17 h after a massive intake.
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