Anticoagulation news items. Weeks commencing 12th September 2016
Spontaneous subarachnoid haemorrhage
The Lancet
This article discusses pathophysiology, diagnosis, management, prognosis and prevention of this uncommon and severe subtype of stroke.
The Lancet
This seminar discusses the diagnosis, specific treatments for acute ischaemic and haemorrhagic stroke. It includes detail on recovery and rehabilitation, as
well as interventions under investigation and future directions.
Scottish Medicines Consortium
The SMC has accepted for use within NHS Scotland, idarucizumab (Praxbind®) for adults treated with dabigatran etexilate, when rapid reversal of its anticoagulanteffects is required for emergency surgery/urgent procedures or in life-threatening or uncontrolled 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:
Anticoagulation news items. Weeks commencing 5th September 2016
International Journal of Clinical Pharmacy
Retrospective cohort study (n=29,338) found among newly anticoagulated patients in real-world setting, initiation with rivaroxaban/warfarin was linked to
greater risk of major bleeding vs. initiation on apixaban. Additional observational studies are required to confirm findings.
Circulation
This review of 11 RCTs (n=33,051) found strong evidence that prolonged dual anti-platelet therapy after implantation of newer-generation drug eluting
stents entails a tradeoff between reductions in stent thrombosis and MI and increases in major hemorrhage.
Warfarin treatment quality and prognosis in patients with mechanical heart valve prosthesis
Heart
This Swedish cohort study evaluating 18,022 patient-years on warfarin showed high INR variability (above ≥0.4) or lower time in therapeutic range (≤70%) was associated with higher risk of bleeding (rate per 100 years 4.33 vs 2.08, HR 2.15 and 5.13 vs 2.30, HR 2.43, 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:
Anticoagulation news items. Weeks commencing 29th August 2016
Heart
Analysis of 19 RCTs (n=87,831) suggests procedure is superior to placebo and antiplatelets, and comparable to NOACs for preventing mortality and stroke/systemic embolism, with similar bleeding risk. However, wide confidence intervals for variables warrants cautious interpretation.
Peri-operative management of anticoagulation and antiplatelet therapy
British Committee for Standards in Haematology
Previous guideline on warfarin (2011) has been updated to include management of patients on direct oral anticoagulants and antiplatelet agents which are
becoming frequent clinical queries. This guideline considers whether and when such agents should be stopped and restarted.
Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy Study
Circulation
Analysisof 11,643 patients noted that continued thienopyridine therapy reduced the rate of MI regardless of optimal medical therapy status and had consistent
effects on reduction in major adverse cardiovascular and cerebrovascular events and increased bleeding.
Heart
Pre-specified 5 year follow-up of 245 of 294 patients (83%) randomised to radiofrequency catheter ablation (RFA) or antiarrhythmic drug therapy (AAD) in MANTRA-PAF trial found that occurrence and burden of any AF and symptomatic AF were significantly lower in RFA group.
Heart
Cohort study (n=70,206 with AF in primary/secondary car, England 1998–2010) noted CHA2DS2-VASc accurately stratifies ischaemic stroke risk, but incidence rate at CHA2DS2-VASc=1 was lower than previously reported, which may change decision to start warfarin in this group.
Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors
New England Journal of Medicine
Descriptive preliminary analysis of study (n=67 with acute major bleeding within 18 hours after administration of factor Xa inhibitor), an initial bolus and subsequent 2-hour infusion of andexanet reduced anti–factor Xa activity, with effective haemostasis occurring in 79%.
The Lancet
In this RCT (n=877) assessing effect of platelet function monitoring with treatment adjustment vs no monitoring, the rate of occurrence of primary endpoint
(composite of CV death, MI, stroke, stent thrombosis, urgent revascularisation and bleeding) did not differ between groups.
Circulation
RCT (n=14,112) showed that addition of ticagrelor 60 mg bd to aspirin in patients with prior myocardial infarction significantly reduced the risk of stroke vs
placebo [HR 0.75 (0.57–0.98) p=0.034] without an excess of hemorrhagic stroke but with more major bleeding.
The Lancet
This RCT (n=2199) showed rates of thromboembolism and major bleeding were low and similar in the 2 treatment groups and across different patient strata,
including those on reduced edoxaban dose due to renal impairment/bodyweight ≤60kg and on concomitant P-glycoprotein inhibitors.
Circulation
In this RCT (n=1230) evaluating prasugrel v ticagrelor prior to PCI, no difference in occurrence of primary endpoint at 7 days (death, re-infarction, urgent target vessel revascularization, stroke, serious bleeding requiring transfusion or prolonging hospitalisation) was noted.
2016 ESC Guidelines for the management of atrial fibrillation
European Heart Journal
The European Society of Cardiology has issued guidance on the diagnosis and management of patients with atrial fibrillation.
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. Weeks commencing 22nd August 2016
The Lancet Haematology
Results from this RCT (n=110) showed that rivaroxaban and warfarin both inhibit thrombin generation in patients with venous thromboembolism and
antiphospholipid syndrome, and rivaroxaban may be an effective alternative to warfarin in this group of patients.
Self‐monitoring and self‐management of oral anticoagulation
Cochrane Database of Systematic Reviews
Review found self-monitoring or self-management can improve quality of oral anticoagulation therapy and reduced thromboembolic events. A reduction in
all-cause mortality was observed in trials of self-management but not in self-monitoring, with no effects on major haemorrhage.
New perspectives on atrial fibrillation and stroke
Heart
The current stroke-prevention strategy in embolic and cryptogenic stroke starts with arrhythmia detection, followed by risk stratification and treatment for
those deemed to be at increased risk. This paper reviews recent findings that challenge this practice paradigm.
The Lancet Neurology
In this RCT of 410 patients comparing mechanical thrombectomy (MT) with standard iv thrombolysis (IVT) vs IVT alone, the addition of MT significantly improved functional independence in patients with acute cerebral ischaemia (p=0.028), with no evidence of increased mortality.
Andexanet Alfa, factor Xa inhibitor antidote, accepted for review by European Medicines Agency (EMA)
Biospace Inc.
The EMA's Committee for Medicinal Products for Human Use will now begin the centralized review procedure for andexanet alfa, a modified human Factor Xa molecule that acts as a decoy to target and sequester both oral and injectable Factor Xa inhibitors in the blood.
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. Weeks commencing 15th August 2016
Journal of the American Heart Association
Combined data from cohort study (n=8013) and meta-analysis (20 trials) found anaemia on admission was linked to increased risk of mortality in both ischaemic stroke (OR 1.97; 95% CI 1.57–2.47) and haemorrhagic stroke (1.46; 1.23–1.74). Targeted interventions may improve outcomes.
British Journal of General Practice
28 survivors of stroke, including 14 accompanying caregivers and five GPs, were interviewed. Medication level barriers included beliefs about medication and
beliefs about how pills work, medication routines, changing medications, and regimen complexity and burden of treatment.
Heart
Japanese study (n=540) found dual antiplatelet therapy (DAPT) group had significantly higher incidence of any bleeding vs. single APT group (36.5% vs 27.5%, p=0.049) and no APT (36.5% vs 21.3%, p=0.010). The no APT group did not experience an increased risk of thrombotic events.
Lancet series on stroke prevention in atrial fibrillation
The Lancet
Lancet has published a clinical series of 3 papers on AF ahead of annual ESC meeting. AF is estimated to affect 33m people worldwide, but this is likely
underestimated since many do not know they have it until they develop symptoms or present with stroke/systemic thromboembolism.
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. Weeks commencing 8th August 2016
National Institute for Health and Care Excellence
DRAFT guidance supports use of ticagrelor 60mg, in combination with aspirin, as continuation therapy for preventing atherothrombotic events in people who
have a history of MI and a high risk of developing atherothrombotic events, only if certain criteria are met.
Heart
This paper provides nationwide data on long-term trends in antithrombotic use, noting it has doubled, mainly due to increased antiplatelet use and introduction of DOACs. Authors discuss how trends in use of individual drugs correlate with publication of landmark studies.
The Lancet
In this study evaluating 15,361 patients of whom 1758 (11%) died within 1 year, heart failure was the most common cause of death (30%) followed by stroke (8%). There were marked unexplained inter-regional variations in the occurrence of stroke and death.
Stability of International Normalized Ratios in Patients Taking Long-term Warfarin Therapy
Journal of the American Medical Association
Research letter describes a study of 3749 patients taking warfarin for atrial fibrillation which found that 26% had 80% or more INR values in the 2.0-3.0
range during the first 6 months. Of these patients, 34% continued to have stable INRs over the next 12 months.
Triple Oral Antithrombotic Therapy (TOAT) - A Teachable Moment
JAMA Internal Medicine
This review, based on a case vignette, discusses the use of TOAT, highlighting steps to reduce bleeding risk are advisable. These include prescribing a
proton pump inhibitor, using lower doses of antiplatelets, and avoiding high-potency P2Y12 inhibitors prasugrel and ticagrelor.
Circulation
This review of the RE-LY trial found that the presence of VHD (n=3,950) did not influence the comparison of dabigatran with warfarin in terms of major bleed
rates and stroke and systemic embolism rates for both the 110mg and 150mg doses.
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. Weeks commencing 25th July 2016 and 1st August 2016
Self-monitoring and self-management of oral anticoagulation therapy
Cochrane Database of Systematic Reviews
Review of 28 RCTs (n=8,950) found a reduction in thromboembolic events in the pooled estimate of self-monitoring or self-management vs standard monitoring (HR, 0.58; 95%CI, 0.45-0.75). No reduction in all-cause mortality or incidence of major or minor haemorrhage was seen.
Economic burden of non-malignant blood disorders across Europe: a population-based cost study
The Lancet Haematology
Non-malignant disorders of the blood cost the 31 European countries €11 billion in 2012. Health-care costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for less than €1 billion (6%).
Heparin for the prevention of intraventricular haemorrhage in preterm infants
Cochrane Database of Systematic Reviews
There is very limited data on effect of prophylactic heparin on incidence and severity of intraventricular haemorrhage (IVH). Both the identified trials used
heparin in the context of maintaining umbilical line patency and not specifically to prevent germinal matrix IVH.
British Journal of Clinical Pharmacology
Study (n=2094) found that frequency of warfarin dose changes and INR monitoring events declined until around age 67, then increased as patients got older.
Heart
In a meta-analysis of 2 randomised and 12 observational studies, there was no benefit of adding a vitamin K antagonist (VKA) with regards to thromboembolism or mortality, versus antiplatelet /no therapy. However, use of a VKA was linked to increased risk of major bleeding.
BMJ Open
Australian study (n=986) found 54 (5.5%) developed venous thromboembolism (VTE), of which 25.9% (14/54) had detected VTE post-hospitalisation with increased risk if there was history of VTE, recent surgery and pulmonary conditions, suggesting potential role of thromboprophylaxis.
National Institute for Health and Care Excellence
In 2017, 30 UK GP practices will test these indicators. GPs will routinely test anyone >65 years for AF and assess how often someone with AF discusses treatment with GP. If these measures are found to improve AF identification/management, they could be rolled out in 2017/18.
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. Weeks commencing 18th July 2016
Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registryDrug Safety Alert: Warfarin - reports of calciphylaxis (syndrome of vascular calcification)
Medicines and Healthcare products Regulatory Agency
An EU-wide review of relevant evidence recently concluded that there is a reasonable possibility that on rare occasions warfarin use might lead to calciphylaxis. Healthcare professionals are advised to consider stopping warfarin and starting appropriate treatment if necessary.
Circulation
This review summarises the evidence around the management of non–vitamin K antagonist (NOACs)-related bleeding, including prevention of bleeding, general principles and supportive measures, nonspecific haemostatic agents, and NOAC-specific reversal agents.
European Heart Journal
Study (n=45,073) found the risk of the primary outcome (composite of all-cause death, re-admission with myocardial infarction or stroke) with ticagrelor vs. clopidogrel was 11.7 vs. 22.3% (HR 0.85 [95% CI: 0.78–0.93]).
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. Weeks commencing 11th July 2016
Precision Medicine for Ischemic Stroke
JAMA Neurology
In this article, the authors discuss the future of precision medicine in the field of ischaemic stroke, first looking at the current status of genetic approaches, and then exploring the status of phenotype-based delineations.
Volunteers wanted to help determine the future of pharmacovigilance
Medicines and Healthcare products Regulatory Agency
Web-RADR: Recognising Adverse Drug Reactions is running a survey for healthcare providers, patients, and consumers of medicines to help develop the next generation of online side-effect reporting software.
New product: ALPROLIX (eftrenonacog alfa) powder and solvent for solution for injection
electronic Medicines Compendium
Eftrenonacog alfa is licensed for the treatment and prophylaxis of bleeding in patients with haemophilia B (congenital factor IX deficiency).
Direct oral anticoagulants: unique properties and practical approaches to management
Heart
This is a review of the indications and dosing considerations, clinical efficacy and safety, laboratory monitoring and reversibility considerations and peri-procedural management of the direct oral anticoagulants (DOACs), highlighting strategies to ensure safe and effective DOAC.
European Medicines Agency
This review has been initiated following a recent study which suggested that inhibitors develop more frequently in patients on factor VIII (F-VIII) medicines made by DNA recombinant technology than in those receiving (F-VIII) derived from blood.
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. Weeks commencing 4th July 2016
Risk of Bleeding and Thrombosis in Patients 70 Years Or Older Using Vitamin K Antagonists
JAMA Internal Medicine
Matched cohort study (n=3313) found compared to patients aged 70-79, those aged 80-89 had similar risk of bleeding, whereas those ≥90 had mildly increased risk of bleeding. Patients in their 80s and 90s had markedly higher risk of thrombosis vs. patients in their 70s.
Journal of the American Medical Association
Chinese study (n=2933) found after day 90 follow-up, clopidogrel-aspirin (CA) reduced the rate of new stroke in the non-carriers but not in carriers of loss-of-function alleles vs aspirin alone.
Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial
Circulation
In this analysis of ENGAGE AF-TIMI 48 study (n=14,071), findings from prespecified renal subgroups defined by a CrCl of 30-50 and >50mL/min were similar to overall trial results in which high dose edoxaban was comparable to warfarin for prevention of stroke/systemic embolism.
The Lancet Haematology
Analysis (n=771 with cancer) found recurrent venous thromboembolism (VTE) occurred in 4% of patients on edoxoban and 7% on warfarin (HR 0.53, 95% CI 0.28-1.00) concluding that edoxoban is non-inferior to warfarin in the treatment of patients with cancer with VTE.
Deep vein thrombosis and pulmonary embolism
The Lancet
This seminar focuses on the epidemiology, diagnosis, and treatment of deep vein thrombosis of the legs and pulmonary embolism as well as looking at future research in this area.
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:
