Anticoagulation news items. Week commencing 21st May 2018
Circulation
Meta-analysis of sub-analysis of RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF trials found in short-term, safety/efficacy of DOACs and warfarin (WF) periprocedurally are not different. DOACs were linked to 38% lower risk of major bleeding vs. WF with uninterrupted anticoagulation.
Cochrane Database of Systematic Reviews
Review of 13 RCTs (n=67,688), most of which involved apixaban, edoxaban, rivaroxaban, found treatment with factor Xa inhibitors significantly reduced number of strokes and systemic embolic events vs. warfarin with AF; the absolute effect vs. warfarin was, however, rather small.
Biospace Inc.
Application relates to use in children under 12 years of age and is based on data from phase 3 prospective TEN02 study in children with moderate to severe deficiency. Coagadex is currently only licensed in UK for use in children over age of 12 years.
PharmaTimes
A 96% and 97% reduction in treated bleed were found in these studies respectively vs no prophylaxis. Emicizumab is currently licensed for routine prophylaxis of bleeding episodes in patients with haemophilia A with factor VIII inhibitors.
Biospace Inc.
This thrombopoietin receptor agonist has been evaluated in ADAPT-1 /ADAPT-2 trials (n=435) which reported higher proportion of patients had increased platelet (PL) counts and did not require PL transfusion/rescue therapy on day of -and up to 7 days after procedure vs. placebo.
Use of Venous Thromboembolism Prophylaxis in Hospitalized Patients
JAMA Internal Medicine
Analysis (n=44,775 in 52 Michigan hospitals) noted anticoagulant (AC) use among low-risk patients (18 584 [57.1%]) was most important contributor to excess use of VTE prophylaxis. Excess use of mechanical VTE prophylaxis was common among both low-and high risk patients.
Journal of the American Heart Association
At 2 yrs, database study (n=19077) found no difference in stroke or systemic embolism (SE) with apixaban or dabigatran (HR=0.78 % 0.94) or major bleeding (0.72 & 0.87) vs warfarin. Rivaroxaban reduced stroke or SE (0.68) without altering major bleeding risk (1.07) vs warfarin.
Revised SPC: Brilique (ticagrelor) – all formulations
electronic Medicines compendium
SPC now states that delayed and decreased exposure to oral P2Y12 inhibitors, including ticagrelor (TG) and active metabolite, has been observed in patients with ACS on morphine (35% reduction in TG exposure). May apply to other opioids; clinical relevance unknown.
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
Anticoagulation news items. Week commencing 14th May 2018
New product: Exembol (argatroban) 1 mg/mL Solution for Infusion - Ready to Use
electronic Medicines compendium
This is a new additional presentation of argatroban (other formulation is multidose 100 mg/ml concentrate that needs to be diluted), which is licensed for anticoagulation in adult patients with heparin-induced thrombocytopenia type II who require parenteral antithrombotic therapy.
Journal of the American College of Cardiology
Study (n=888) which was prematurely stopped, suggests personalised approach to selecting antiplatelet may reduce ischaemic and bleeding events [primary endpoint occurred in 71 (15.9%) in pharmacogenomic and 114 (25.9%) in standard-of-care arm; HR 0.58;95% CI; 0.43-0.78;p <0.001].
The Lancet Neurology
Study (n=1447) found that in patients with AF anticoagulated after recent ischaemic stroke /TIA, cerebral microbleed presence is linked to symptomatic intracranial haemorrhage risk (HR 3.67,95% CI 1.27–10.60 vs.absence microbleeds) and could help inform anticoagulation decisions.
The Lancet Neurology
RCT (n=1534 from 3 Asian countries) reported cilostazol was non-inferior to aspirin for the prevention of cardiovascular events (HR 0.80, 95% CI 0.57–1.11; non-inferiority p=0.0077); but did not reduce the risk of haemorrhagic stroke(HR 0.51, 97.5% CI 0.20–1.27).
Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA
New England Journal of Medicine
RCT (n=4,881) found that clopidogrel plus aspirin was associated with a lower risk of major ischaemic events vs aspirin alone at 90 days (5% vs 6.5%, HR 0.75, p=0.02) but an increased risk of major haemorrhage (0.9% vs 0.4%, 2.32, p=0.02).
MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset
New England Journal of Medicine
RCT was stopped early owing to cessation of funding (n=503 from 800 anticipated). Favourable outcome (score of 0 or 1 on the modified Rankin scale of neurologic disability) was reported in 53.3% given altepase vs 41.8% for placebo (adjusted OR 1.61, p=0.02).
Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source
New England Journal of Medicine
RCT (n=7,213) was terminated early due to lack of benefit in stroke risk and worse bleeding outcomes for rivaroxaban vs aspirin (annualised major bleeding with rivaroxaban was 1.8% vs 0.7% for aspirin, HR 2.72, p<0.001).
The Lancet
RCT (n=2.325) found no difference in functional status at day 90 (primary outcome) for tranexamic acid vs placebo (adjusted OR 0.88, 95% CI 0.76 to 1.03), although there were fewer deaths by day 7 with tranexamic acid (9% vs 11% 0.73, 0.53 to 0.99).
Management of Bleeding in Patients Taking Oral Anticoagulants
Journal of the American Medical Association
This US decision pathway from the American College of Cardiology details management of patients who experience either life-threatening bleeding or major bleeding at a critical site. Ceasing the anticoagulant, supportive measures and reversal agents are the major strategies.
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
Anticoagulation news items. Week commencing 7th May 2018
Journal of Clinical Oncology
RCT (n=203) found that rivaroxaban was associated with relatively low venous thromboembolism VTE recurrence vs dalteparin (6 month recurrence rate 11% vs 4%; HR 0.43; 95% CI, 0.19 to 0.99). Corresponding 6 months rates of clinically relevant non-major bleeding were 4% vs 13%.
British Journal of Clinical Pharmacology
Of 328 Italian patients, 143 were inappropriately prescribed with oral anticoagulants (OACs), 88 of which were under prescribed or prescribed with an inappropriate drug. Among 55 of 221 patients prescribed OACs, dosing errors were the most frequent cause of inappropriate use.
European Journal of Hospital Pharmacy
This retrospective observational study identified 37 hospitalisation episodes for DOAC-induced bleeding in 32 patients (15 rivaroxaban, 9 apixaban and 8 dabigatran; incidence rate 3.44 [95% CI 2.35 to 4.86] per 100 person-years), most commonly gastrointestinal (27 cases, 73.0%).
Stability of repackaged dabigatran etexilate capsules in dose administration aids
European Journal of Hospital Pharmacy
Repackaged capsules stored in the refrigerator for 28 days had a drug content of 98.2% and dissolution was not significantly affected (p=0.132). If repackaging of Pradaxa capsules is required, storage under refrigerated conditions ensures quality for 28 days.
Periprocedural management of patients receiving novel oral anticoagulants
European Journal of Hospital Pharmacy
This review of guidelines and evidence for the use of non-vitamin K oral antagonists highlights discrepancies between US and European guidelines. However, consensus about postoperative resumption is clear: 24 and 48–72hours, after low- and high-risk bleeding surgery, respectively.
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
Anticoagulation news items. Week commencing 30th April 2018
New England Journal of Medicine
Calciphylaxis is a life-threatening syndrome of vascular calcification characterised by occlusion of microvessels in the subcutaneous adipose tissue and dermis. This review presents current understanding of the condition and provides a framework for interdisciplinary management.
Antifibrinolytic drugs for treating primary postpartum haemorrhage
Cochrane Database of Systematic Reviews
Review of data from 3 RCTs (n=20,412) concludes tranexamic acid, when administered intravenously, reduces mortality due to bleeding in women with primary postpartum haemorrhage, irrespective of mode of birth, and without increasing the risk of thromboembolic events.
Treatment for superficial thrombophlebitis of the leg
Cochrane Database of Systematic Reviews
Review of 33 RCTs (n=7296) concludes prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for superficial thrombophlebitis of the legs for most people. Evidence on topical treatment/surgery is too limited and cannot inform clinical practice.
American Journal of Hematology
Results from these RCTs (n=150) show that stable responses (defined as platelets ≥50,000/μL at ≥4 of 6 biweekly visits) occurred in 18% of patients on fostamatinib vs. 2% on placebo (P=0.0003). Median time to response was 15 days (on 100mg bd).
British Journal of Clinical Pharmacology
Genotype‐guided dosing (GGD; n=5230) reduced time‐to‐first therapeutic INR (mean 2.6 days; P<0.0001; I2 0%) and time‐to‐first stable INR (5.9 days; P<0.01; I2 94%) vs conventional dosing. GGD also increased time in therapeutic range and reduced risks of INR ≥ 4 and 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:
http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services
