Anticoagulation news items. Week commencing 29th April 2019
National Institute for Health and Care Excellence
This guideline covers interventions in the acute stage of a stroke or transient ischaemic attack (TIA). It offers the best clinical advice on the diagnosis and acute management of stroke and TIA in the 48 hours after onset of symptoms.
Outpatient versus inpatient treatment for acute pulmonary embolism
Cochrane Database of Systematic Reviews
Low‐quality evidence (2 RCTs; n= 451) suggests that there is no clear difference between the interventions in overall mortality, bleeding and recurrence of pulmonary embolism.
Optimal Timing of P2Y12 Inhibitor Loading in Patients Undergoing PCI: A Meta-Analysis
Thrombosis and Haemostasis
Review of 23 studies (n=60,907) reported that early P2Y12 inhibitor loading (> 2 hours pre-PCI) was associated with better outcomes vs versus late (< 2 hours pre-PCI or post-PCI; RRR; 22% for MACE, 30% for MI, 25% for death; all p<0.001), without an impact on major bleeding.
JAMA Neurology
Secondary analysis of POINT RCT (n= 4881) reported a low risk of major hemorrhages in patients receiving either clopidogrel plus aspirin or aspirin alone (0.9% vs 0.2%; HR, 3.57; P = 0.003; NNH, 159). However, risk was still increased with dual therapy vs aspirin monotherapy.
Arthritis & Rheumatology
Review of 2 databases (n=50,865) found that occurrence of venous thromboembolism when initiating treatment with tofacitinib or a TNF inhibitor was infrequent (<1 per 100 person‐years), with no statistically significant difference in risk between the two treatments.
Circulation
This review discusses developments in the roles of platelets and coagulation factors in atherothrombosis and addresses the rationale and clinical evidence for combining antiplatelet and oral anticoagulant therapy in patients with coronary and peripheral artery disease.
The Lancet
Analysis (20 RCTs;n=26,616) found risk of primary outcome was reduced with new-generation drug-eluting vs. bare-metal stents (HR 0.84, 95% CI 0.78–0.90,p<0·001) due to reduced risk of MI (HR 0·79,0·71–0·88;p<0.001) and possible slight but non-significant cardiac mortality benefit.
Circulation
Paper describes the derivation and validation of a prediction model for ischaemic stroke/ systemic embolism (SE) and major bleeding in patients with AF from the 3 treatment arms of the RE-LY trial (n=11,955 in derivation cohort, n=6,158 in validation cohort).
Atrial fibrillation type and renal dysfunction as important predictors of left atrial thrombus
Heart
In a real-world population of patients with AF, most on oral anticoagulation, left atrial appendage (LAA) thrombus was found in ~6%. Two variables not included in CHA2DS2-VASc score (AF type and renal dysfunction) proved strong, independent predictors of LAA thrombus.
Mayo Clinic Proceedings
Study of 227 patients with mean CHA2DS2-VASc score 4.3, and HAS-BLED score 2.3, found negligible correlation between patient perceived and estimated risk of stroke (r=0.07; p=0.32), and bleeding (r=0.16; p=0.02). Most patients overestimated their risks of stroke 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
Anticoagulation news items. Week commencing 15th and 22nd April 2019
JAMA Cardiology
Analysis (n=5022) found over median follow-up of 19.6months, fewer patients on rivaroxaban (vs placebo) had thromboembolic event (TE) including sudden/unwitnessed deaths (SWD; 13.1 vs 15.5%; HR 0.83; 95% CI, 0.72-0.96; p=0 .01). When SWD were excluded, results on TEs were similar.
Thromboembolism After Shoulder Arthoplasty and Arthroscopy
Journal of the American Academy of Orthopaedic Surgeons
Review notes that symptomatic VTE after shoulder surgery is an apparently rare but serious event; risk is higher after shoulder arthroplasty than arthroscopy. Asymptomatic VTE is more common. Prevention strategies should balance the risks of VTE with the risks of treatment.
Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery
Cochrane Database of Systematic Reviews
Review of 7 RCTs (n=1,728) found that prolonged thromboprophylaxis significantly reduces the risk of VTE vs thromboprophylaxis during hospital admittance only (5.3% vs 13.2%, OR 0.38, 95% CI 0.26-0.54), without increasing bleeding complications or mortality.
Stroke
Review of 10 RCTs (n=15,434) comparing aspirin vs clopidogrel (A+C) to aspirin alone found that short term (≤1 month) & intermediate term A+C (≤3 month) reduced the risk of recurrent stroke and major cardiovascular events, but long term A+C was not associated with benefit.
British Journal of General Practice
Study (n=4.943) found antiplatelets were linked to a higher risk of stroke or TIA vs vitamin K antagonists (VKAs) (HR 1.51, 95% CI 1.09-2.09) as well as to an increased risk of GI haemorrhage (1.79, 1.01-3.18). The risk was similar for those on direct oral anticoagulants or VKAs.
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 1st and 8th April 2019
Revised SPC: FibCLOT (human fibrinogen) injection/infusion
electronic Medicines compendium
SPC has now been updated to detail the licence extension for paediatric use.
Anticoagulation therapy in heart failure and sinus rhythm: a systematic review and meta-analysis
Heart
Analysis of 5 trials found anticoagulation (AC) reduced rate of non-fatal stroke (RR 0.63, 95% CI, 0.49-0.81, p=0.001) but increased major haemorrhage (1.88; 1.49-2.38, p=0.001). AC did not reduce all-cause mortality, heart failure (re)hospitalisation or non-fatal MI, vs. control.
JAMA Neurology
RCT (n=7112) found HAVOC score, left atrial diameter (LAD), and premature atrial contraction frequency predicted subsequent clinical AF. Among subgroup with LAD >4.6 cm (9% overall population), risk of ischaemic stroke was lower in rivaroxaban vs. aspirin group (1.7 vs 6.5%/year).
Circulation
With availability of DOACs, authors have seen large increases in anticoagulation (AC) rates, but considerable gaps in guideline adherence remain among high-risk patients. Article shares practical strategies to address common barriers to initiating/maintaining AC in this group.
Oral anticoagulation among atrial fibrillation patients with anaemia: an observational cohort study
European Heart Journal
Observational cohort-study of 18,734 anaemic AF patients suggests treatment with oral anticoagulants increased rate of major bleeding and reduced time in therapeutic range with no reduction in risk of stroke/thromboembolism particularly among patients with moderate/severe anaemia.
BMJ Open
Study of 5310 pts receiving a VKA and 3156 pts receiving a NOAC found that abnormal liver function, prior stroke or TIA, labile INR, therapy with antiplatelet or NSAIDs, heart failure and age ≥75 yrs were independently associated with thromboembolic and major bleeding events.
Direct oral anticoagulation and mortality in moderate to high-risk atrial fibrillation
Heart
Retrospective analysis of patients (n=11,314) with non-valvular atrial fibrillation reports DOAC therapy was associated with a significantly lower risk of death compared with no oral anticoagulation: 7.6% vs 11.1% per year respectively (HR=0.69, p<0.001).
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 18th and 25th March 2019
electronic Medicines compendium
Sections 4.4 and 4.5 now advise isohemagglutinins may interfere with serological tests. Additionally, the SPC advises of increased risk of thrombotic microangiopathy with FEIBA in patients receiving emicizumab prophylaxis.
Revised SPC: Revolade (eltrombopag) film-coated tablets – all strengths
electronic Medicines compendium
The SPCs have been updated with information related to liver functions tests, thrombotic and thromboembolic complications and myelodysplastic syndrome.
Journal of Thrombosis and Haemastasis
Review of 8 studies reporting data on 1994 thrombophilia patients found no statistically significant differences in rate of VTE recurrence for DOACs vs vitamin K antagonists (RR 0.79, 95% 0.34-1.44). Bleeding event rates were similar (0.92, 0.62 to 1.36).
Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation
New England Journal of Medicine
2 x 2 factorial RCT (n=4,614) found that in those with AF and a recent MI or PCI on a P2Y12 inhibitor; apixaban, without aspirin, resulted in less bleeding and without affecting the incidence of ischaemic events vs regimens including a vitamin K antagonist and/or aspirin.
Direct Oral Anticoagulant (DOAC) Dosing in renal impairment
Drug and Therapeutics Bulletin
In light of > 4,000 yellow card reports of DOAC-associated haemorrhagic events since their launch, the author of this editorial highlights the urgent need for national guidance to help clinicians prescribe DOACs safely, particularly for patients with declining renal function.
British Medical Journal
Cardiovascular system disorders | Haematological disorders
Neither company admitted liability. Most plaintiffs argued that rivaroxaban's labelling and instructions did not provide adequate information about risk to patients and clinicians. Janssen said labelling had been approved by US FDA and "clearly communicated benefits and risks."
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 11th March 2019
European Heart Journal
Danish registry review of 46,301 pts on dual antiplatelet treatment after MI found only 35% at higher risk of upper gastrointestinal (UGI) bleeding received treatment with PPI based on the guideline criteria. Use of a PPI was associated with a lower 1-year risk of UGI bleedings.
Antithrombotic therapy in patients undergoing transcatheter aortic valve implantation
Heart
Review summarises currently available data and suggests a more individualised antithrombotic treatment strategy after transcatheter aortic valve implantation based on risk factors for cardiovascular events and bleeding.
PharmaTimes
The decision follows results of the Phase III HAVEN 3 study. Emicizumab is already licensed for routine prophylaxis of bleeding episodes in patients with haemophilia A with factor VIII 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:
http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services
Anticoagulation news items. Week commencing 4th March 2019
JAMA Internal Medicine
US registry-based cohort study (n=6539) reports 37.5% received combination warfarin and aspirin without therapeutic indication for aspirin use; compared with matched controls, higher rates of overall bleeding were reported for those on combination (26.0% vs 20.3%; P<0.001).
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 25th February 2019
NIHR Signal: Prolonging anticoagulant treatment after abdominal cancer surgery reduces clot risk
National Institute for Health Research Signal
An expert opinion is provided of a Cochrane review which concluded that the incidence of venous thromboembolism was reduced in people who have low molecular weight heparin (LMWH) for between two to four weeks after abdominal or pelvic surgery, especially for cancer.
Annals of Internal Medicine
This is an evaluation of prognostic bleeding risk models, with a view to developing a model to be used to estimate the absolute bleeding harms of aspirin among persons in whom aspirin is being considered for the primary prevention of CVD.
JAMA Neurology
This RCT (n=250) reports risk of recurrent stroke at 1 year was 2.5%, with no difference in recurrence rates or rates of angiographic recanalisation with either antiplatelets or anticoagulants.
European Heart Journal
Pre-specified sub-group analysis (n=2725) reported that benefits of dabigatran dual therapy vs warfarin triple therapy in reducing bleeding risks were consistent across subgroups of patients with or without acute coronary syndrome, and patients treated with ticagrelor or clopidogrel.
Acute dual antiplatelet therapy for minor ischaemic stroke or transient ischaemic attack
British Medical Journal
BMJ analysis discusses recent evidence and recommends that dual antiplatelet therapy should be started as soon as possible within 24 hours of minor ischaemic stroke or high risk transient ischaemic attack and should be continued up to 21 days.
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 18th February 2019
American Journal of Medicine
Study (n=14,407) found during median 1.6 months follow-up, concomitant DOAC-antiplatelet (vs. Vit K antagonist-antiplatelet) linked to similar GI bleeding risk but decreased intracranial bleed risk (HR 0.46; 95% CI, 0.24-0.91) and other major bleeding (0.68; 95% CI, 0.51-0.91).
Turoctocog alfa pegol for Haemophilia A approved for use in the US
Biospace Inc.
Approval was on the basis of a trial which found that turoctocog alfa pegol provided effective prophylaxis and that patients were able to maintain a low median annualised bleeding rate of 1.18 on maintenance dosing. It is currently under regulatory review for use in the EU.
Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis
New England Journal of Medicine
This RCT in which 2003 adults in ICU were randomised to either pharmacologic thromboprophylaxis alone or in combination with intermittent pneumatic compression, reports no statistically significant difference in incident proximal lower-limb DVT, or death from any cause at 90 days.
Circulation
Post-hoc analysis involving 1985 patients ≤60kg, 15,172 patients in the mid-range weight group and 982 patients >120kg reports treatment effect of apixaban vs warfarin for efficacy outcomes of stroke/systemic embolism, all-cause death, or MI was consistent across weight spectrum.
Intracerebral haemorrhage during alemtuzumab administration
The Lancet
In this letter, the authors describe the presentation of patients with intracerebral haemorrhage, and suggest that patients whose mean systolic BP increases >20mmHg (or 20% or more throughout the infusion period), might be at high risk of intracranial haemorrhage.
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 11th February 2019
Pharmacist-led virtual clinics to optimise anticoagulation in AF
Public Health England
Over a 12-month period, the programme reviewed over 1500 patients with AF not receiving anticoagulation, which resulted in an additional 1,200 patients being anticoagulated. The 2 CCGs (Lambeth and Southwark) have since seen a 25% reduction in the rate of AF-related stroke.
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 4th February 2019
Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors
New England Journal of Medicine
Cohort study of 352 patients with acute major bleeding associated with the use of a factor Xa inhibitor, reported that andexanet reduced anti–factor Xa activity by 93% from baseline, and that 82% of patients achieved haemostatic efficacy at 12 hours.
The Lancet
RCT reported no change in functional status at 90 days with intensive (target systolic BP 130–140 mm Hg within 1 h) or guideline-recommended (target <180 mm Hg) BP lowering therapy over 72 h in 2227 alteplase-eligible patients with acute ischaemic stroke.
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
