Revised SPCs: Eliquis (apixaban) film-coated tablets- all strengths
electronic Medicines compendium
SPCs highlight DOACs are not recommended for patients with history of thrombosis diagnosed with antiphospholipid syndrome, in particular, triple positive patients, where use of DOACs could be associated with increased rates of recurrent thrombotic events vs. vitamin K antagonists.
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
Circulation
Analysis of data from the COMPASS RCT (n=27,395) found that in heart failure patients specifically (5,902 patients), rivaroxaban plus aspirin was similarly superior to aspirin alone as per the overall trial population.
Evaluation of the Incidence of New-Onset Atrial Fibrillation After Aortic Valve Replacement
JAMA Internal Medicine
This population-based study reports new-onset AF was present in 50% of hospitalisations for transcatheter aortic valve implantation and aortic valve replacement. It advises shared patient-doctor decision making regarding potential need for anticoagulation after these procedures.
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
The Lancet Haematology
Retrospective analysis of data evaluating safety and efficacy of direct oral anticoagulants and warfarin in 795 morbidly obese patients (BMI>40kg/m2) suggests concludes similar efficacy and safety of apixaban and rivaroxaban, compared to warfarin in patients with AF and VTE.
European Heart Journal
Study (n=1,859) showed no significant difference in major cardiovascular events occurring in 9.7% ticagrelor patients vs. 8.2% aspirin patients [HR 1.19; 95% CI 0.87–1.62; p= 0.28]), or in major bleeding. RCT was terminated early & underpowered however due to recruitment issues.
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
Journal of Clinical Oncology
Observational study of 695 patients with cancer and incidental diagnosis of PE suggests despite anticoagulant therapy, recurrent VTE occurred in 6% of patients, strengthening current guideline advice to treat incidental PE as symptomatic PE for at least 3 to 6 months.
The Lancet
RCT (n=537) reports 4% of participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage vs 9% allocated to avoid antiplatelet therapy (HR 0.51, p=0.060), whilst 7% and 9% of patients respectively experienced major haemorrhagic events (HR 0.71, p=0.27).
Circulation
The consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.
The Lancet
Review of 3 RCTs (n=414) found that more patients given alteplase achieved excellent functional outcomes at 3 months vs placebo (36% vs 29%, OR 1.86, p=0.011). Intracerebral haemorrhage was more common with alteplase (5% vs 1%, OR 9.7, p=0.031).
Revised SPC@ Pradaxa (dabigatran etexilate mesilate) hard capsules (all strengths)
electronic Medicines compendium
Section 4.4 has been updated to include a warning regarding thromboembolic risk in patients with antiphospholipid syndrome.
Medicines and Healthcare products Regulatory Agency
Following an increased risk of pulmonary embolism and overall mortality with tofacitinib 10 mg twice-daily in the study A3921133 rheumatoid arthritis study, a safety review has started and this dose (authorised for ulcerative colitis) is contraindicated in patients at high risk of VTE.
European Heart Journal
Study suggests that early discharge with continuation of rivaroxaban at home is safe and effective in certain low-risk patients with acute PE. Rate of symptomatic recurrent VTE or PE-related death within 3 months (primary outcome) occurred in 3 of 525 patients (0.6%; P <0.0001).
The rise and fall of aspirin in the primary prevention of cardiovascular disease
The Lancet
This narrative review discusses the role of aspirin in primary prevention of cardiovascular disease, contextualising data from historical and contemporary trials.
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
Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source
New England Journal of Medicine
RCT (n=5390) found that dabigatran was not superior to aspirin in preventing recurrent stroke, which occurred in 6.6% (4.1%/year) and 7.7% (4.8%/year), of patients, respectively. Incidence of major bleeding was not significantly greater in dabigatran group (1.7 vs. 1.4%).
JAMA Neurology
Review of 13 RCTs (n=134,446) reports low-dose aspirin use among individuals without symptomatic cardiovascular disease (primary prevention) was associated with an increased risk of any intracranial bleeding especially in Asians, or people with a low body mass index.
Cochrane Database of Systematic Reviews
Review found 2 RCTs of 59 haemophiliacs only and reports beneficial effect of systemically administered tranexamic acid & epsilon aminocaproic acid in preventing postoperative bleeding. Definite efficacy in oral or dental procedures however is uncertain, due to limited evidence.
Less dementia and stroke in low-risk patients with atrial fibrillation taking oral anticoagulation
European Heart Journal
Study (n=91,254 with baseline CHA2DS2-VASc score ≤ 1) reports treatment with oral anticoagulation was associated with lower risk of dementia (subhazard ratio 0.6, 95% CI 0.48–0.81) in people aged >65 years; but the risk: benefit profile in <60 years is not so favourable.
Fragmin (dalteparin sodium) approved by FDA as first anticoagulant for children
PharmaTimes
The FDA has approved use in paediatric patients' ≥ 1 month of age to reduce recurrence of symptomatic venous thromboembolism. Approval was based on a single trial of 38 children with symptomatic deep vein thrombosis and pulmonary embolism treated with Fragmin for up to 3 months.
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
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
Spontaneous haemorrhage on apixaban masquerading as obstructive cholangitis after heart surgery
European Heart Journal
This case was a 73-year-old with a presentation of obstructive cholangitis, likely secondary to migration of blood into the common bile duct as a complication of apixaban (2.5 mg 2×/day) 16 days post coronary artery bypass grafting.
American Journal of Cardiology
Review (5 studies, n=28,135) reports DOACs have superior efficacy compared to warfarin in reducing stroke or systemic embolisation (HR 0.76, 95% CI 0.67 to 0.86, p <0.01). Apixaban appeared to have the best benefit vs risk profile in this population.
Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke
New England Journal of Medicine
RCT (n=225) found use of alteplase between 4.5 and 9.0 hours after stroke onset resulted in higher proportion of patients with no/minor neurologic deficits vs placebo (35.4 vs.29.5%;risk ratio, 1.44; 95% CI, 1.01 to 2.06; p=0.04) but more cases of symptomatic cerebral 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
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
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
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
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
