Anticoagulation news items. Weeks commencing 10th October 2016
European Heart Journal
Analysis of registry data (2011–15) found that among 43, 299 anticoagulant-naïve AF patients, treatment with NOACs was not linked to significantly lower risk of stroke/thromboembolism vs. vitamin K antagonist but intracranial bleeding risk was lower with dabigatran and apixaban.
Specialist Pharmacy Service
This Q&A offers guidance on what factors should be considered when calculating a low molecular weight treatment dose following a venous thromboembolism in non-pregnant adult patients with a high body weight, defined as more than 120kg.
The Lancet Neurology
In this study of 96 patients, the primary outcomes (30 day mortality, 7 day procedure-related mortality, 72h symptomatic bleeding, and 30 day brain
infections) did not differ between the standard medical care vs minimally invasive surgery + alteplase groups.
US Food and Drug Administration
In July 2016, Alere INRatio device, which was used to monitor warfarin in control group of trial was recalled due to potential to generate inaccurate results.
Following series of analyses, FDA has determined effects on strokes or bleeding, including cerebral bleeds were minimal.
Thrombosis and Haemostasis
This study (n=45,361) found that apixaban and dabigatran were associated with a lower risk of major bleeding vs warfarin (HR 0.53, 95% CI 0.39-0.71 and 0.69, 0.50-0.96). Compared to apixaban, rivaroxaban was associated with higher risk of major bleeding (1.82, 1.36-2.43).
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Anticoagulation news items. Weeks commencing 3rd October 2016
JAMA Internal Medicine
This analysis of 118 891 atrial fibrillation patients taking rivaroxabanor dabigatran reports that those treated with rivaroxaban were more likely to experience both intracranial haemorrhage or major extracranial bleeding than those treated with dabigatran.
The Handbook of Perioperative Medicines
UK Clinical Pharmacy Association
This handbook, in the form of drug monographs, contains information on how medicines are to be managed in the peri-operative period. It has been developed collaboratively by clinical pharmacy experts, to address the need for a national guidance for healthcare professionals.
The Lancet Oncology
In this review, the authors provide the first evidence-based international guidelines on direct oral anticoagulant use in the treatment of VTE. These guidelines
aim to address in-hospital and outpatient cancer-associated VTE in specific subgroups of patients with cancer.
The Lancet
Review of 8 RCTs (n=963) found that low-molecular-weight heparin (LMWH) does not seem to reduce risk of recurrent placenta-mediated pregnancy complications vs. no LMWH in at-risk women. However some decreases in event rates might have been too small for power of study to explore.
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Anticoagulation news items. Weeks commencing 26th September 2016
BMJOpen
Study (n=15,242) found observed differential prescribing of oral anticoagulants (OACs) can result in channeling bias in comparative effectiveness research.
Persistence patterns changed over follow-up time, apixaban had improved persistence rates vs. other OACs.
The Lancet Haematology
Study (n=57, with 72 vaginal bleeding events) found vaginal bleeding, particularly heavy menstrual bleeding, is a common complication in women of reproductive age on direct oral factor Xa inhibitor therapy. Most cases can be treated conservatively.
British Medical Journal
Investigation found companies were aware of concerns about faulty INRatio device, which could have put participants at unnecessary risk. It asks whether regulatory investigations could have been avoided, who was informed, FDA's concerns, and whether trial results can be trusted.
Does tranexamic acid improve outcomes in traumatic brain injury?
British Medical Journal
Review notes efficacy/safety is uncertain, although RCTs are under way. It suggests intracranial bleeding could be reduced but risk of cerebral thrombosis and
ischaemia might increase with treatment. It does not support use in routine clinical practice unless RCTs show benefit.
Novel oral anticoagulants for atrial fibrillation
British Medical Journal
Editorial notes use has proved to be highly variable in patients most at risk, (4%-70% in different areas in England), which may partly be due to clinical
uncertainty about balance of benefit to harm, and which cannot be resolved until independent scrutiny of key trial data.
New oral anticoagulants for stroke prevention in atrial fibrillation: Infographic
Pharmaceutical Journal
This infographic covers the anticoagulant effect of these agents, the slow rise of prescribing, the individual agents, and deciding which one to prescribe.
British Medical Journal
RCT (n=7123) found a bivalirudin monotherapy strategy vs. heparin with or without glycoprotein IIb/IIIa inhibitors, did not result in reduced major adverse
cardiovascular events or net adverse clinical events in patients with or without ST segment elevation.
Valvular heart disease and pregnancy: management of prosthetic valves
Heart
This review discusses the pregnancy risks in women with prosthetic heart valves, strategies for anticoagulation in women with mechanical heart valves, and the management of complications.
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Anticoagulation news items. Weeks commencing 19th September 2016
electronic Medicines Compendium
This product is licensed for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). This preparation does
not contain von Willebrand factor and is therefore not indicated in von Willebrand's disease.
Revised SPC: Haemoctin (Human plasma derived coagulation factor VIII)
electronic Medicines Compendium
Special warning for use in patients with existing cardiovascular risk factors has been added, which states that substitution with factor VIII may increase the
cardiovascular risk.
Edoxaban drug–drug interactions with ketoconazole, erythromycin, and cyclosporine
British Journal of Clinical Pharmacology
Report of 3 drug-drug interaction studies notes administration of dual inhibitors of P-gp and CYP3A4 increased edoxaban exposure by less than two-fold. Effect
appears to be primarily due to P- gp inhibition and impact of CYP3A4 inhibition appears to be less pronounced.
A systematic review of tranexamic acid in hip fracture surgery
British Journal of Clinical Pharmacology
Analysis of 7 studies (n=770) found moderate quality evidence that tranexamic acid reduces blood transfusion in hip fracture surgery vs. placebo (RR: 0.54; 95% CI: 0.35–0.85), with low quality evidence suggesting no increased risk of thrombotic events.
Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation
Heart
This analysis (UK) of 39,670 newly diagnosed AF patients showed that since NOACs were introduced, there has been an increase in patients receiving
guideline-recommended therapy, predominantly driven by increased use of NOACs and reduced use of other antithrombotics.
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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.
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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).
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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.
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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.
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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.
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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.
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