Anticoagulation news items. Week commencing 26th October 2020
Journal of the American Medical Association
Study (n=31,290 propensity matched pairs) reports the 1-yr risk of net adverse clinical events was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; hazard ratio, 1.05 [95% CI, 1.00-1.10]; p=.06).
Revised SPC: Alprolix (eftrenonacog alfa) powder and solvent for solution for injection
electronic Medicines compendium
Factor IX inhibition, hypersensitivity and Injection site erythema have been added as common adverse events.
Journal of the American Medical Association
In 596 critically ill patients, anticoagulation with regional citrate, increased filter life span vs systemic heparin anticoagulation (47 vs 27 hours) but the trial was underpowered to reach conclusions regarding mortality (90-day mortality 51.2% vs 53.6%).
Fibrosis, atrial fibrillation and stroke: clinical updates and emerging mechanistic models
Heart
Review outlines the clinical knowledge in this setting, alongside computational modelling frameworks which may provide a mechanistic understanding of the clinical problem of thromboembolisation.
Thrombosis Research
Review (7 studies; n=2364) found that in comparison to vitamin-K antagonists, rivaroxaban has potential to reduce post-thrombotic syndrome events [OR 0.53, 95% CI: 0.43–0.65, p<0.00001], but well-designed studies with larger sample sizes are needed to corroborate these findings.
Clinical and budget impacts of changes in oral anticoagulation prescribing for atrial fibrillation
Heart
English study found that despite nearly one million additional DOAC prescriptions and substantial associated spending in the latter part of this study, the decline in AF-related stroke (fell by 11.3%) led to incremental savings (£289 per-patient) at the national level.
The Lancet Neurology
Study (n=100) does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth (occurred in 26 [52%] placebo vs. 22 [44%] tranexamic acid group; OR 0·72;95% CI 0·32–1·59, p=0.41), although treatment was safe with no increase in thromboembolic complications.
Anticoagulation in atrial fibrillation
Heart
Review notes 1 in 3 people will be diagnosed with AF at some point in their lives; over 1.2m individuals in UK have been diagnosed with AF; thousands still remain undiagnosed, and risk of AF-related stroke can be mitigated through anticoagulation, with a 66% risk reduction.
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 19th October 2020
Rituximab for treating inhibitors in people with inherited severe haemophilia
Cochrane Database of Systematic Reviews
This review did not identify any relevant randomised controlled trials. The research evidence available was limited to case reports and case series therefore no conclusions could be drawn on the efficacy and safety of rituximab for treating inhibitors in people with haemophilia.
Topline Phase III data of avatrombopag for treatment of chemotherapy-induced thrombocytopenia
Biospace Inc.
Though avatrombopag increased platelet counts relative to placebo, the study did not meet the composite primary endpoint of avoiding platelet transfusions, chemotherapy dose reductions by 15% or greater, and chemotherapy dose delays by four days or more.
Cessation of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation
Heart
In 'real world' cohort (n=1415), persistence of DOAC use was found to be high with only 8.8 cessations/100 patient-years follow-up and rate of serious adverse events rate was low at 1.6/100 patient-years; most common cause of cessation of index DOAC (53.1%) was patient choice.
JAMA Neurology
Analysis (n=3699) found those with cerebral microbleeds had higher rates of recurrent stroke, ischaemic stroke, intracerebral haemorrhage, and mortality during 11 months of follow-up, but this did not appear to influence the effects of rivaroxaban (15mg) on clinical outcomes.
Circulation
This narrative review discusses recent trials that inform the current use of aspirin in the secondary prevention of chronic coronary syndrome (CCS), a new term for stable coronary artery disease defined in the 2019 European Society of Cardiology guidelines.
Revised SPC: Praxbind (idarucizumab) 2.5 g/50 mL solution for injection/infusion
electronic Medicines compendium
Section 5.1 has been updated with information on a paediatric patient (between 16-<18 years old) treated with idarucizumab during an open-label safety trial.
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 October 2020
Warfarin and other anticoagulants – monitoring of patients during the COVID-19 pandemic
Medicines and Healthcare products Regulatory Agency
MHRA has published guidance following concerns over an apparent increase in the number of patients taking warfarin found to have elevated INR values during the pandemic; and reminds healthcare professionals and patients that continued close INR monitoring is crucial.
JAMA Neurology
Viewpoint from US perspective notes the situation of an acute stroke emergency is a particularly vulnerable situation for exposure and transmission of COVID-19; it advocates for expanded usage of tenecteplase as means of avoiding spread and easing potential shortages of alteplase.
Circulation
RCT (n=727) found pre-hospital administration of loading dose of crushed prasugrel tablets does not improve TIMI 3 flow in infarct-related artery pre-PCI or complete ST-segment resolution 1h post-PCI vs. intact tablets, and there were no differences in ischaemic events at 30 days.
Thrombosis Research
Study of INR results show significant increase in high INRs during COVID-19 pandemic, with majority occurring after introduction of lockdown, with 30/3214 (0.9%) INR samples >8.0 (n=30) vs. 6/4079 (0.1%; n=6) during same period in previous year (OR 6.3, 95% CI, 2.6–15.2; p<0.001).
Warfarin in patients with mechanical heart valves
British Medical Journal
Practice article highlights these patients require lifelong anticoagulation with warfarin to prevent thromboembolism, low dose aspirin can be added in patients with higher risk of thromboembolic events, and DOACs are not currently recommended as safety has not been established.
Healthcare Safety Investigation Branch
Follow review of a case of a 78-year old woman who suffered a pulmonary embolism whilst recovering from a stroke in hospital, this report makes a safety recommendation for a stroke specific venous thromboembolism assessment tool.
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 5th October 2020
Cochrane Database of Systematic Reviews
This review (15 RCTs; n=17,091) concludes multiple antiplatelet drugs reduced risk of stroke recurrence (5.78% v 7.84%, RR 0.73, 95% CI 0.66-0.82; P<0.001) but increased risk of bleeding (e.g. extracranial haemorrhage 6.38% vs 2.81%, RR 2.25, 95% CI 1.88-2.70; P<0.001).
American Society of Hematology
The DRAFT guidelines, agreed by an international panel, suggest using prophylactic-intensity over intermediate-intensity or therapeutic-intensity anticoagulation in patients with COVID-19 related critical illness or acute illness who do not have suspected or confirmed VTE.
Antiphospholipid Antibodies in Critically Ill Patients With COVID‐19
Arthritis & Rheumatology
Study (n=66) found antiphospholipid antibodies (APSA) were common (47%) in patients in critical condition (CC) but were not present among those not in CC. APSA may be transient & disappear in few weeks, but in genetically predisposed, may trigger condition similar to APS syndrome.
Cochrane Database of Systematic Reviews
Review (44 RCTs, n=3196) found moderate‐certainty evidence that shows antifibrinolytics & combined hormonal contraceptives reduce heavy menstrual bleeding vs. placebo; and low‐certainty evidence that antifibrinolytics are more effective vs. NSAIDs/short‐cycle progestogens.
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 28th September 2020
Dabigatran trough concentrations in very elderly patients
European Journal of Hospital Pharmacy
Observational study of 75 patients with atrial fibrillation, found trough concentrations were considerably higher in the highest age category. Dose-normalised medians were 0.66, 0.83 and 1.20 ng/mL/mg in the <75, 75–84 and ≥85 age groups, respectively (p=0.004).
NIHR Alert: Tranexamic acid should not be used for patients with severe gastrointestinal bleeding
National Institute for Health Research
Expert commentary is provided on the HALT-IT (Haemorrhage alleviation with tranexamic acid-Intestinal system) trial of more than 12,000 patients; which showed tranexamic acid does not improve outcomes but increases side effects for this group of patients compared to placebo.
JAMA Cardiology
Secondary analysis of RCT (n=4129) found risk of major vascular events was greater than 10% over 30 months for high risk patients and treatment with combination of rivaroxaban and aspirin vs aspirin alone resulted in estimated 4.2% absolute risk reduction for major vascular event.
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 21st September 2020
The Lancet Haematology
Meta-analysis of individual participant data from 14 of 20 eligible RCTs (n=8278) found LMWH was associated with a lower VTE risk (adjusted RR 0.58; 95% CI 0.47-0.71), but there was no survival benefit. Risk of minor bleeding (1.34; 1.19-1.51), but not major, was increased.
NICE issues draft updated guideline on the management of atrial fibrillation
National Institute for Health and Care Excellence
This DRAFT guideline, which will update CG180 (published June 2014), will cover the diagnosis and management of AF in adults. It aims to ensure people receive the best care to help prevent complications, such as a stroke, and side effects of treatment, such as bleeding.
Cochrane Database of Systematic Reviews
Updated review identified 2 studies (n=1135) and noted they did not provide evidence to support this use; and studies did not report on the outcome of catheter occlusion, days of catheter patency, episodes of catheter‐related bloodstream infection and other side effects.
JAMA Cardiology
In prespecified analysis of RCT (n=171), occurrence & severity of migraine attacks (MAs) decreased over time with low percentage of patients with MAs at 6-12-month follow-up; only 1% with new-onset MAs after cessation of clopidogrel at 3 months after atrial septal defect closure.
Vonicog alfa for the treatment and prevention of bleeding in adults with von Willebrand disease
NHS England
NHS England will commission vonicog alfa for the treatment and prevention of bleeding in adults with von Willebrand disease in accordance with the criteria outlined in these documents.
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 14th September 2020
European Journal of Hospital Pharmacy
Spanish retrospective cohort study reported higher risk of bleeding with dalteparin in patients with renal insufficiency (RI) vs those with normal renal function (n=367; 17.9% vs 7.3%) and identified RI (MDRD-4 (Modification of Diet in Renal Disease) <50 mL/min) as a risk factor.
Specialist Pharmacy Service
This Q&A offers guidance on what factors should be considered when calculating a LMWH treatment dose following a VTE in non-pregnant adult patients with a high body weight, defined as more than 120 kg.
Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy
Cochrane Database of Systematic Reviews
Updated review (8 studies;n= 3818) found there is a small risk that healthy adult patients undergoing knee arthroscopy will develop venous thromboembolism & there is moderate‐ to low‐certainty evidence of no benefit from use of LMWH, aspirin or rivaroxaban in reducing this risk.
Premature permanent discontinuation of apixaban or warfarin in patients with atrial fibrillation
Heart
Posthoc analysis of ARISTOTLE found premature permanent discontinuation of study drug was common, less frequent in patients on apixaban than warfarin and followed by high 30-day rates of death, TED &major bleeding, but no significant difference in clinical outcomes between groups.
Cochrane Database of Systematic Reviews
This review (11 studies; n=1672) found the combination of heparin plus aspirin during the course of pregnancy may increase live birth rate in women with persistent antiphospholipid antibodies compared to aspirin treatment alone; safety is uncertain due to the lack of reporting.
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 7th September 2020
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.
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.
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.
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
Anticoagulation news items. Week commencing 31st August 2020
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.
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.
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.
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.
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.
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
Anticoagulation news items. Week commencing 17th and 24th August 2020
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.
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
