Anticoagulation news items. Week commencing 23rd September 2019
Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Asians With Atrial Fibrillation
Stroke
Review, based on subanalyses of 5 RCTs and 21 observational cohorts, found use of NOACs is noninferior vs warfarin with respect to risk of stroke or systemic embolism, all-cause mortality, major bleeding and intracranial bleeding, irrespective of the NOAC type and dose.
BMJ Open
Database study (n=30 467; 2011-2016) reported 76.9% of patients starting NOACs were prescribed an appropriate dose. Underdosing more frequent in apixaban vs dabigatran and rivaroxaban cohorts. Overdosing more frequent in dabigatran vs rivaroxaban or apixaban cohorts.
Thrombosis Reasearch
Retrospective US study of 2890 matched pairs of morbidly obese VTE patients reported similar recurrent VTE risk (OR: 0.99; 95% CI: 0.85–1.14) and major bleeding (0.75: 0.47–1.19) with rivaroxaban vs warfarin. Hospitalizations and outpatient visits were lower with rivaroxaban.
Oral Anticoagulation in patients with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1
European Heart Journal
This report outlines the currently available evidence in this field and provides a risk stratification of the individual thromboembolic risk in patients with AF and a CHA2DS2-VASc score of 1 to guide clinicians on whether to anticoagulate or not.
Revised SPC: Brilique (ticagrelor) film coated tablets – all strengths
electronic Medicines compendium
The SPC has been updated to warn of potential for ticagrelor to interfere with platelet function tests to diagnose heparin induced thrombocytopenia (HIT).
Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery
Cochrane Database of Systematic Reviews
Updated review of 7 RCTs (n=1728) concludes prolonged thromboprophylaxis (14 days) with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality.
JAMA Neurology
Pooled analysis of data from 251 patients with mild-deficit emergency large-vessel occlusion stroke concludes mechanical thrombectomy has a similar efficacy and safety profile vs best medical management, and a separate systematic review confirms this finding.
Circulation
Study (n=4,614) shows regimen of apixaban + P2Y12 inhibitor without aspirin provides superior safety & similar efficacy in atrial fibrillation patients who have ACS (managed medically or with PCI), or those undergoing elective PCI; vs. regimens with VKAs, aspirin, or both.
Heart
Study (n=159,222) found the female/male ischaemic stroke risk ratio varied with age. Only women aged >75 years had a higher risk, whereas women aged <65 years had a lower risk vs. men. Authors state findings challenge the 'sex category' of the CHA2DS2-VASc score.
Ticagrelor with or without Aspirin in High-Risk Patients after PCI
New England Journal of Medicine
RCT (n=7,119) found ticagrelor monotherapy was associated with lower incidence of clinically relevant bleeding vs. ticagrelor + aspirin (1.0% vs. 2.0%; HR 0.49; 95% CI, 0.33 to 0.74), with no higher risk of death, myocardial infarction, or 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:
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Anticoagulation news items. Week commencing 16th September 2019
Stroke and thromboembolism prevention in atrial fibrillation
Heart
Review discusses this association, medical/non-medical therapy for stroke prevention, guideline recommendations for prevention, electrical and pharmacological cardioversion, ablation therapy and antithrombotic medication management, as well as key outstanding research questions.
Annals of Internal Medicine
This study, based on an analysis of 245,028 persons (43.6% women) aged 30-79yrs without established CVD who had their CVD risk assessed suggests a model that provides a personalised prediction of the benefits and bleeding harms from aspirin when used for primary prevention of CVD.
Head injury: assessment and early management – updated guideline [CG176]
National Institute for Health and Care Excellence
Updates have been made to the recommendations on head CT scans in people on anticoagulant treatment, diagnosis and management of post head injury hypopituitarism, and management of indirect brain injuries.
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:
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Anticoagulation news items. Week commencing 9th September 2019
Bleeding and New Cancer Diagnosis in Patients with Atherosclerosis
Circulation
Study (n=27,395) found that in patients with atherosclerosis treated with antithrombotic drugs, any GI bleeding was linked to new GI cancer diagnosis (HR 20.6, 95% CI, 15.2 to 27.8); likewise for genitourinary(GU) bleeding and new GU cancer diagnosis (32.5; 24.7 to 42.9).
Thrombosis and Haemostasis
Review of 9 RCTs (n=7,656) found that rivaroxaban reduced VTE vs aspirin (1.3% vs 3.5%, RR 0.36, 95% CI 0.26-0.48), but increased non-major bleeding (11.5% vs 7.5%, 1.28, 1.13-1.44). There was no difference in all-cause mortality and major bleeding.
Annals of Internal Medicine
Meta-analysis of registry data from 5 countries concludes prevalence of hemophilia is higher than previously estimated: prevalence (per 100,000 males) is 17.1 cases for all severities of haemophilia A, and 3.8 cases for all severities of haemophilia B.
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Anticoagulation news items. Week commencing 2nd September 2019
JAMA Neurology
RCT (n=120) found no recurrent VTEs and one major bleeding event with dabigatran and two with warfarin. Authors conclude that both may be effective for recurrent VTE prevention in patients with central venous thrombosis.
Journal of the American Medical Association
RCT (n=1,650) failed to establish non-inferiority of an INR goal of 1.8 vs 2.5 for VTE prevention post hip or knee arthroplasty (rate of VTE or death was 5.1% for INR target of 1.8 vs 3.8% for INR target 2.5, difference 1.3%, p=0.06 for non-inferiority).
A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI
New England Journal of Medicine
Open label RCT (n=2,488) found a similar efficacy outcome (composite of stent thrombosis, mortality and myocardial infarction) for a CYP2C19 genotype–guided strategy vs standard ticagrelor or prasugrel, but minor bleeding rates were lower (9.8% vs 12.5% p=0.04).
The Lancet
RCT (n=1,506) found that edoxaban was non-inferior to a vitamin K antagonist (VKA) for bleeding events (annualised rate of 20.7% for edoxaban vs 25.6% for VKAs, HR 0.83, 95% CI 0.65-1.05, non-inferiority margin HR = 1.20, p=0.001 for non-inferiority).
British Journal of Clinical Pharmacology
This review gives background information on critical factors for the formulary uptake process of LMWHs. It introduces a straightforward instrument to enhance formulary policy making in a transparent, rational way (the System of Objectified Judgment Analysis/Infomatrix model).
The Lancet Oncology
This guidance is based on a systematic review of the literature. Results from head to head trials comparing DOACs with LMWHs are included for information in the guidance along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.
Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease
New England Journal of Medicine
Study of 2236 AF patients reports rivaroxaban monotherapy is non-inferior to combination therapy with antiplatelet+rivaroxaban for the primary efficacy end point (composite of stroke, systemic embolism, MI, unstable angina requiring revascularization, or death from any cause).
European Heart Journal
Predicted individual gain in life expectancy free of stroke or MI from added low-dose rivaroxaban had a median of 16 months (range 1–48 months), while predicted individualized lifetime lost in terms of major bleeding had a median of 2 months (range 0–20 months).
Ticagrelor in Patients with Stable Coronary Disease and Diabetes
New England Journal of Medicine
RCT (n=19,220; median follow-up 39.9 months) reported lower incidence of ischaemic cardiovascular events with ticagrelor + aspirin vs aspirin (7.7 vs. 8.5%; HR, 0.90; 95% CI, 0.81 to 0.99; P=0.04) but higher incidence of major bleeding (2.2 vs. 1.0%; 2.32; 1.82 to 2.94; P<0.001).
Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes
New England Journal of Medicine
Open-label RCT (n=4018) reported incidence of death, MI, or stroke was significantly lower in the prasugrel group vs ticagrelor group (6.9% vs 9.3%; HR, 1.36; 95% CI, 1.09 to 1.70; P=0.006) with no difference in major bleeding (4.8% vs 5.4%; 1.12; 0.83 to 1.51; P=0.46).
The Lancet
Sub-group analysis (n=11,154) reported that addition of ticagrelor to aspirin reduced cardiovascular death, MI, and stroke vs placebo for a median of 3.3 years (7.3 vs 8.6% in the PCI group; HR 0.85; 95% CI 0.74–0.97; p=0.013), although with increased risk of major bleeding.
European Heart Journal
These guidelines, an update of the 2014 guidelines, outline the optimal diagnosis, assessment, and treatment of patients with pulmonary embolism.
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:
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Anticoagulation news items. Week commencing 26th August 2019
Gastroenterology
RCT (n=17,598 followed up for median 3.01 years, with 53,152 patient-years of follow-up) found no statistically significant difference between pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% placebo group; OR 1.33; 95% CI, 1.01–1.75).
Increasing number of patients prescribed risky anticoagulant drug combinations
Pharmaceutical Journal
Statistics from the Medication Safety Dashboard show that between Sept 18 and Nov 18, there were more than 14,000 patients in England prescribed an NSAID with an anticoagulant and more than 30,000 patients prescribed an antiplatelet and anticoagulant without gastro-protection.
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:
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Anticoagulation news items. Week commencing 19th August 2019
The Lancet Haematology
Review (25 RCTs) found that vs no prophylaxis, rivaroxaban was most effective for prevention of DVT (RR 0.12; 95% CI 0.06–0.22). LMWH, vs no prophylaxis was found to be more effective for pulmonary embolism and best for major bleeding but these findings are highly uncertain.
NHS England
NHS England will commission emicizumab as prophylaxis in adults and children with severe congenital haemophilia A (defined as factor VIII level <1 IU/dL, or <1% of normal) without current inhibitors to prevent bleeding episodes.
Catheter Ablation for Atrial Fibrillation in 2019
Journal of the American Medical Association
This article reviews management approaches to atrial fibrillation (AF), including assessment of the need for anticoagulation, and controversies over the need for rhythm control and the role of catheter ablation for maintaining sinus rhythm and reducing AF-associated symptoms.
Annals of Internal Medicine
RCT (n=184) found patients on continuous anticoagulants +cold snare polypectomy (CSP;without electrocautery) did not have increased incidence of polypectomy-related major bleeding, and procedure time and hospitalisation were shorter vs. periprocedural heparin bridging plus hot SP.
JAMA Neurology
RCTs included 69 patients and found that recombinant activated coagulation factor VII did not significantly improve radiographic or clinical outcomes vs. placebo among patients with spot sign–positive intracerebral haemorrhage treated a median of ~3 hours from stroke onset.
JAMA Neurology
Analysis of POINT and CHANCE trials (n=10,051) found clopidogrel-aspirin treatment reduced risk of major ischaemic events at 90 days vs. aspirin, that appeared to be confined to the first 21 days (5.2% vs 7.8%; HR 0.66; 95% CI, 0.56-0.77; p <0 .001), but not from day 22 to day 90.
Stroke
Review of 3 RCTs and 15 observational studies (total n=23,478) found that DOACs were associated with less major bleeding and major cardiovascular adverse effects, but vitamin K antagonists were associated with decreased mortality and 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:
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Anticoagulation news items. Week commencing 12th August 2019
The Lancet Haematology
Study (93 children) found that bodyweight adjusted rivaroxaban appears to be safe in children (no major bleeds, 4% rate of non-major bleed and no recurrent VTEs). Doses for <20kg showed low exposure, so the dosages for this group will be adjusted for the phase 3 study.
American Journal of Medicine
Analysis of 14 RCTs(n=164,751) found aspirin decreases MI risk at expense of increased risks for major bleeding (BD) and haemorrhagic stroke. With contemporary aggressive preventive strategies, effect on MI risk seems to be much attenuated whereas its harmful effects on BD remain.
National Institute for Health Research
Expert commentary is provided of UK trial of 537 adults (RESTART) on antiplatelets before intracerebral haemorrhage, which found no material difference in risk of further bleeding or occlusive vascular event if they restarted on the drugs when feasible.
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:
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Anticoagulation news items. Week commencing 5th August 2019
NIHR Signal: Reminders to assess clotting risk increase the use of preventive measures
National Institute for Health Research
Expert commentary is provided for a review of 13 RCTs (n=35,997) which found that alert based interventions increased the proportion of patients who received mechanical or drug prophylaxis vs standard care. Unfortunately, trial data are lacking on multifaceted interventions.
The Lancet Neurology
Scottish cohort study (n=300) found antithrombotic therapy linked to lower risk of subsequent intracranial haemorrhage (ICH) or focal neurological deficit. Meta-analysis of 6 cohort studies (n=1342) also noted lower ICH risk (3 vs. 14%; IRR 0.25; 95% CI,0.13–0.51;p<0.0001).
American Journal of Cardiology
Analysis of 6 trials (n=8855) found no significant difference in major adverse CV event in patients on oral anticoagulant (OAC) plus single antiplatelet therapy (SAPT) vs. OAC monotherapy. OAC plus SAPT was linked to higher risk of major bleeding (HR 1.61; 95% CI 1.38-1.87).
Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant
JAMA Internal Medicine
Cohort study (n=3007) followed up post-operatively for 30 days suggests DOAC therapy interruption without heparin bridging or coagulation function testing before elective surgery were associated with low rates of major bleeding (<2%) and arterial thromboembolism.
Journal of Clinical Oncology
This updated guideline now recommends thromboprophylaxis with apixaban, rivaroxaban, or low molecular weight heparin to selected high-risk outpatients with cancer, whilst rivaroxaban and edoxaban have been added as options for VTE treatment.
European Heart Journal
Study (n=962) found that thromboembolic risk increased in 30 days before cardioversion and persisted until 30 days post-cardioversion (0.47% and 0.96%, respectively; HR 2.2, 95% CI 0.7–7.1). Authors suggest that this increased risk may not be entirely causal.
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:
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Anticoagulation news items. Week commencing 29th July 2019
Revised SPC: Xarelto (rivaroxaban) tablets
electronic Medicines compendium
SPC now advises that rivaroxaban should not be used for thromboprophylaxis in patients having recently undergone transcatheter aortic valve replacement as the safety and efficacy have not been studied in this population.
Bayer
Bayer has published a checklist for prescribers, a Q&A on important information for women and a summary of important information about risk of blood clots with combined hormonal contraceptives, for all Bayer CHC products.
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:
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Anticoagulation news items. Week commencing 22nd July 2019
JAMA Neurology
Data from 11,662 patients discharged after stroke shows those on DOACs (v warfarin) had fewer deaths (HR 0.88, P<0.001), all-cause readmissions (0.93; P=0.003), CV readmissions (0.92, P=0.02), haemorrhagic strokes (0.69, P=0.02), and hospitalisation with bleeding (0.89, P=0.009).
British Medical Journal
Review (18 studies;n=7515) found in patients with 1st episode unprovoked VTE who completed ≥3 months anticoagulation, risk of recurrent VTE was 10% in 1st year after treatment, 16% at 2 years, 25% at 5 years, and 36% at 10 years, with 4% of recurrent VTE events resulting in death.
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:
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