Anticoagulation news items. Week commencing 6th April 2015
Biospace Inc.
The US FDA has filed an application seeking approval of dabigatran for the prophylaxis of DVT and PE in patients who have had primary elective total hip replacement surgery, based on the results of two Phase III trials (RE-NOVATE and RE-NOVATE II) comparing it to enoxaparin.
Investigational anticoagulant reversal agent (PER977) receives FDA Fast Track designation
Biospace Inc.
The FDA has granted Fast Track status for PER977, an investigational anticoagulant reversal agent that directly binds to NOACs, fondaparinux, low molecular weight heparins and unfractionated heparins. It is undergoing development as an IV injection; Phase III studies are planned.
Eyes on Evidence: Detecting atrial fibrillation in people who have had a stroke
National Institute for Health and Care Excellence
A commentary is provided on 2 RCTs which reported that long-term ECG monitoring was more effective at detecting AF than 24-hour or intermittent ECG monitoring in people who had experienced apparent cryptogenic stroke or transient ischaemic attack.
Antiphospholipid syndrome: A patient’s journey
British Medical Journal
This is last in a series of occasional articles by patients about their experiences that offer lessons to doctors. It illustrates the often long delays
experienced by patients before a diagnosis is made and treatment started.
Journal of the American Medical Association
Based on 16 trials (n=12 890) there was no difference between LMWH and unfractionated heparin in their associations with mortality, pulmonary embolism, symptomatic DVT, major bleeding, or minor bleeding outcomes in patients with cancer undergoing surgical procedures.
Practice Guide for managing a high INR in a patient on warfarin
British Medical Journal
This practice guide, based on a case vignette, outlines the immediate and long-term management of a patient presenting with a high INR whilst on
warfarin.
CADTH reviews point-of-care INR testing compared with laboratory INR testing
Canadian Agency for Drugs and Technologies in Health
This review summarises the practical impact of, and cost effectiveness of point-of-care (POC) INR testing compared with lab INR testing concluding that patient self-management (POC INR testing + dose adjustment) may be the most cost-effective option, when feasible, in Canada.
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:
Anticoagulation news items. Week commencing 30th March 2015
Stroke
Shortening door-to-needle time may lead to inadvertent intravenous thrombolysis (IVT) administration in stroke mimics (SMs). Prospective, single-centre experience (n=75) coupled with findings of meta-analysis of 9 studies suggest safety of IVT in SMs.
European Heart Journal
The article discusses dual antiplatelet therapy (DAPT), stable coronary artery disease, acute coronary syndromes, novel evidence, stent types and DAPT, rebound after DAPT cessation, and individualised DAPT management.
Cangrelor (Kengrexal™) approved in the EU for use in patients undergoing PCI
Biospace Inc.
The EC has granted marketing authorisation for cangrelor (Kengrexal™) for the reduction of thrombotic cardiovascular events in adults with coronary artery disease undergoing PCI and who have not received an oral P2Y12 inhibitor prior to the procedure.
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:
Anticoagulation news items. Week commencing 23rd March 2015
The Lancet Neurology
Pre-specified analysis (n=3017) found some early ischaemic and pre-existing signs are linked to reduced independence at 6 months and increased symptomatic intracranial haemorrhage. No interaction was noted between brain imaging signs and effects of alteplase on these outcomes.
National Institute for Health and Care Excellence
Rivaroxaban is recommended as an option within its marketing authorisation, in combination with aspirin plus clopidogrel or aspirin alone, for preventing atherothrombotic events in people who have had an acute coronary syndrome with elevated cardiac biomarkers.
British Medical Journal
US data reported that pre-procedural risk stratification was associated with an increase in the uptake of bleeding avoidance strategies (bivalirudin, radial approach, and vascular closure devices) leading to a reduction in rates of bleeding, particularly among high risk patients.
Microbleeds, Mortality, and Stroke in Alzheimer Disease: The MISTRAL Study
JAMA Neurology
This longitudinal cohort study found that microbleeds in patients with Alzheimer disease increased the risk of CV events (non-lobar bleeds) and stroke (lobar bleeds) and related mortality – even higher risks for such events were found in patients using antithrombotics.
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:
Anticoagulation news items. Week commencing 16th March 2015
The Lancet
This meta-analysis concluded that shorter DAPT was associated with lower all-cause mortality compared with longer DAPT (HR 0.82, 95% CI 0.69–0.98; p=0.02; NNT=325). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of MI and stent thrombosis.
Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction
New England Journal of Medicine
At 3 years, composite CV death, MI or stroke was reduced in the ticagrelor groups vs placebo (HR 90mg ticagrelor 0.85, 95%CI 0.75-0.96; P=0.008; HR 60mg 0.84; 0.74-0.95; P=0.004). Rates of TIMI major bleeding were higher with ticagrelor than with placebo.
The Lancet
This paper, the first in a series of three papers, discusses the pharmacological properties of the most commonly used oral antithrombotic drugs, and explores the development of antiplatelet and anticoagulant therapies.
Clinical evidence for oral antiplatelet therapy in acute coronary syndromes
The Lancet
This paper, the second in a series of three, describes major trial results for oral antiplatelet use in ACS, implications for clinical practice, and
summarises continuing controversy.
The Lancet
This paper (the third in a series of three) addresses the role of anticoagulation for stroke prevention in AF in the era of NOACs, focussing on special situations including management in the event of bleeding and around the time of procedures.
Journal of the American Medical Association
Among patients with AMI undergoing primary PCI (n=2194), the use of bivalirudin post-procedure resulted in a decrease in net adverse clinical events vs both heparin alone and heparin + tirofiban (8.8% vs 13.2% and 17% respectively, p statistically significant for both).
UKMi
This updated Medicines Q&A evaluates the evidence available on the risk of gastrointestinal bleeding with selective serotonin reuptake inhibitors.
Journal of the American Medical Association
In 1687 patients with bare metal stents who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months versus placebo did not result in significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding.
National Institute for Health and Care Excellence
Discussion of a UK GP population based randomised trial (the INTERACT trial) of people taking blood pressure and/or lipid–lowering medicines for the prevention of cardiovascular disease (CVD) which assessed the value of text messaging for medicines adherence.
Thrombolysis in acute ischaemic stroke: time for a rethink?
British Medical Journal
The authors of this article consider the use of alteplase in the management of acute stroke. They say the evidence suggests use at 3-4.5 hours after onset increases mortality with no clear benefit and believe that current recommendations should be re-evaluated urgently.
Medicines and Healthcare products Regulatory Agency
In people with certain medical conditions, these devices can give low blood coagulation results, which can lead to incorrect anticoagulant dose. This alert advises action to be taken by those working in anti-coagulation clinics and device users or their carers.
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:
Anticoagulation news items. Week commencing 9th March 2015
British Medical Journal
This research finds guideline recommendations often don't consider potential drug-drug or -disease interactions that may be present if patients have co-morbidities. The authors call for guideline developers to more explicitly account for multimorbidity in their recommendations.
Revised SPC: Plavix™ (clopidogrel) tablets
Annals of Emergency Medicine
Section 4.8 has been updated to include two new undesirable effects - acute generalised exanthematous pustulosis (very rare) and gynaecomastia (rare).
Scottish Medicines Consortium
The SMC has accepted apixaban (Eliquis) for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of recurrent DVT and PE in adults.
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:
Anticoagulation news items. Week commencing 2nd March 2015
Cochrane Database of Systematic Reviews
There is insufficient evidence from randomised controlled trials to assess the most effective and safe haemostatic treatment to prevent bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgical procedures.
The Lancet Neurology
By sequentially combining cardiac monitoring methods, AF might be newly detected in ~25% patients with CVA/TIA. Proportion with CVA known to have AF seems higher than previously estimated, so more could be treated with oral anticoagulants and more CVA recurrences prevented.
European Medicines Agency
The European Medicines Agency has approved vorapaxar (Zontivity®) for use in combination with aspirin and, where appropriate, clopidogrel, for the reduction of atherothrombotic events in adult patients with a history of myocardial infarction.
JAMA Stroke
Analysis of data from 17 trials (n=42,234, follow up 4 wks-3.5 yrs) found that use of any single antiplatelet agent was linked to significant reduction in recurrence of any stroke (risk ratio 0.77, 0.62–0.97, 2 trials) and ischaemic stroke (0.48, 0.30–0.78, 2 trials) vs. placebo.
The Lancet
In 14,171 patients, digoxin (DG) was used at baseline in 5239 (37%). DG was linked to significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. A randomised trial of DG in treatment of AF patients with and without heart failure is needed.
National Institute for Health and Care Excellence
DRAFT guidance supports use of apixaban, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults. Anticipated publication date of guidance is June 2015.
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:
Anticoagulation news items. Week commencing 23rd February 2015
European Heart Journal
This study(n=1970) suggests clinical presentation may be treatment modifier with respect to DAPT duration post stenting consistent with theory that stable CAD but not ACS-patients are exposed to significant increase in bleeding/net adverse clinical events with 24 vs. 6-month therapy.
Journal of the American College of Cardiology
RCT in good aspirin responders which was prematurely terminated due to recruitment problems (n=941 on 24-month and 953 on 6-month DAPT), found that rates of bleeding and thrombotic events were not significantly different between the 2 groups after PCI with new-generation DES.
The Lancet
RCT (n=181) found addition to vitamin K (VK) of single dose of four-factor prothrombin complex concentrate was non-inferior and superior to addition of plasma for rapid INR reversal and effective haemostasis in patients needing VK antagonist reversal pre-operatively.
Factor Xa inhibitor antidote andexanet alfa receives orphan drug designation in US
Biospace Inc.
Andexanet alfa is intended for reversing anticoagulant effect of direct or indirect factor Xa inhibitors in patients experiencing a serious uncontrolled bleeding event or who require urgent or emergent surgery. Currently, there is no approved antidote for these patients.
The Lancet Neurology
This Scottish RCT in 104 (71 analysed) adults with supratentorial ischaemic stroke eligible for intravenous thrombolysis within 4.5 hours of onset found that neurological and radiological outcomes did not differ between the tenecteplase and alteplase groups.
Journal of the American Medical Association
This retrospective cohort study of patients with oral anticoagulant (OAC)-associated ICH found reversal (INR <1.3 within 4 hours) and systolic
BP <160mmHg at 4 hours were associated with reduced rates of haematoma enlargement, and OAC resumption reduced rates of ischaemic events.
Journal of the American Medical Association
An analysis of Danish registry data (n=61,971) found that use of NSAIDs among adults receiving antithrombotic therapy after a first MI was associated with an increased risk of bleeding requiring hospitalisation (HR 2.02) and an excess of cardiovascular events (HR 1.40).
Venous Thromboembolism - Reducing the risk: addendum consultation
National Institute for Health and Care Excellence
NICE is currently updating its guidance on 'Venous thromboembolism - reducing the risk' following new evidence identified on intermittent pneumatic compression for preventing VTE in hospitalised stroke patients. New DRAFT recommendations have been published for consultation.
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:
Anticoagulation news items. Week commencing 16th February 2015
Vorapaxar in Patients With Diabetes and Prior MI: Findings from the TRA 2°P-TIMI 50 Trial
Circulation
In this subgroup analysis of patients with DM and recent MI (n=3,623), vorapaxar reduced the composite primary endpoint of CV death, MI, or stroke at 3 years (11.4% vs. 14.3%, HR 0.73, 95% CI 0.60-0.89; p=0.002) with a number needed to treat to avoid 1 major CV event of 29.
European Heart Journal
In this subgroup analysis of patients with/without prior VKA exposure, higher-dose edoxaban reduced risk of stroke or systemic embolic events in patients who were VKA naive (HR 0.71, 95% CI 0.56–0.90) and was similar to warfarin in the VKA experienced (HR 1.01, 0.82–1.24; P=0.028.
Journal of the American Medical Association
Swedish registry data (40,616 consecutive patients with NSTEMI) identified that fondaparinux was associated with lower odds than LMWH of major bleeding events and death both in-hospital and up to 180 days afterwards. These data are consistent with trial data.
Stroke
PPIs evaluated in this study (esomeprazole, lansoprazole, omeprazole, rabeprazole) of 325,559 concomitant users of clopidogrel and a PPI, did not increase the rate of ischaemic stroke vs. pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel.
Atrial fibrillation: quality standard consultation
National Institute for Health and Care Excellence
This quality standard for adults with atrial fibrillation (AF) is expected to contribute to improvements in rates of: mortality, stroke and transient ischaemic attack, admission with a primary diagnosis of AF, and quality of life.
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:
Anticoagulation news items. Week commencing 9th February 2015
The Lancet Neurology
Pilot study data (n=250) found no difference in efficacy of antiplatelet and anticoagulant drugs at preventing stroke and death in patients with symptomatic carotid and vertebral artery dissection. However, stroke events were rare in both groups.
National Institute for Health and Care Excellence
Discussion of a systematic review which has identified those medicines reported in the literature that most commonly cause serious adverse reactions because of medication errors.
Biospace Inc.
A variation in Marketing Authorisation has been submitted to the EMA for the use of eltrombopag (Revolade) for the treatment of children >1 year with chronic immune (idiopathic) thrombocytopenic purpura who have had an insufficient response to corticosteroids or immunoglobulins.
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:
Anticoagulation news items. Week commencing 2nd February 2015
National Institute for Health and Care Excellence
Discussion of a systematic review and meta-analysis published in 2014 in the American Journal of Cardiology which explored whether apixaban is superior to conventional agents with regard to bleeding complications in the subset of people with renal failure.
British Medical Journal
Among 12, 403 older Canadian adults with AF who started warfarin, rates of major bleeding were significantly higher in those with lower eGFR, particularly during the first 30 days of treatment. The NNH was 22 during the first 30 days vs 206 in the remainder of the follow-up.
Revised SPC: Revolade (eltrombopag)
electronic Medicines Compendium
Section 4.8 (undesirable effects) has been updated based on the latest pooled analysis of adverse events/ adverse drug reactions for ITP-controlled trials.
JAMA Neurology
This retrospective analysis found that use of thrombolysis after mild stroke (poorly represented in thrombolytic trials) was associated with infrequent complications; however 30% could not ambulate independently at discharge and 29.4% could not go directly home.
Revised SPC: Pradaxa tablets (dabigatran etexilate mesilate) – all strengths
electronic Medicines Compendium
Sections 4.8 and 5.1 have been updated to include new safety and efficacy data.
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
