Anticoagulation news items. Week commencing 2nd May 2017
Trends in the prescription of novel oral anticoagulants in UK primary care
British Journal of Clinical Pharmacology
Data from the UK CPR Datalink (between 2009-2015) shows the overall rate of oral anticoagulant initiation increased by 58% over the study period despite the rate of new VKA use decreasing by 31%. The rate of initiation of NOAC increased, with a 17-fold increase from 2012 to 2015.
Gastrointestinal Safety of Direct Oral Anticoagulants: A Large Population-Based Study
Gastroenterology
This study (n=43,303) found GI bleeding occurred more frequently with rivaroxaban than dabigatran (HR, 1.20; 95% CI, 1.00-1.45), whereas apixaban was associated with lower bleeding risk than dabigatran (0.39; 0.27-0.58; P <0.001) or rivaroxaban (0.33; 0.22-0.49; P < 0.001).
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Anticoagulation news items. Week commencing 24th April 2017
American Journal of Cardiology
Meta-analysis of 9 RCTs (n= 106,288) suggests that overall, ticagrelor may have the best net efficacy and safety profile among currently approved oral P2Y12 inhibitors for the treatment of acute coronary syndrome.
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Anticoagulation news items. Week commencing 10th and 17th April 2017
European Heart Journal
This analysis of UK data reports that all three diseases were associated with an increased risk of venous thromboembolism, highest for rheumatoid arthritis (HR 1.29; 95% CI 1.18–1.39 for no DMARD and 1.35, 95% CI 1.27–1.44 for DMARD). An interaction with DMARDs was significant.
Treatment of Patients With Atrial Fibrillation and Heart Failure With Reduced Ejection Fraction
Circulation
This review discusses the available data for the treatment of AF in patients who have heart failure with reduced ejection fraction, looks at areas where more investigation is necessary, and presents suggestions for individualised treatment strategies for specific patient groups.
European Heart Journal
Review of 5 RCTs (n=1,730) found that patients treated with bioresorbable vascular scaffolds had a higher risk of device thrombisis vs those treated with everolimus eluting stents (OR 2.93, 95% CI 1.37-6.26). There was no statistical difference in risk of target lesion failure.
NIHR Signal: Thrombolysis may reduce complications of deep vein thrombosis
National Institute for Health Research Signal
Expert commentary is provided for a systematic review which found that thrombolysis reduced the risk of post-thrombotic syndrome. This benefit however would come at the cost of and increased risk of bleeding. The role of thrombolysis in deep vein thrombosis requires clarification.
Anticoagulation reversal for supratherapeutic International Normalized Ratio: A teachable moment
JAMA Internal Medicine
This article describes a case report of a woman in her 80s who underwent anticoagulation reversal, and highlights that fresh frozen plasma transfusions in certain patients with non-urgent conditions can lead to transfusion-associated circulatory overload.
Potent P2Y12 Inhibitors in Men Versus Women A Collaborative Meta-Analysis of Randomized Trials
Journal of the American College of Cardiology
Meta-analysis of 7 studies (n=87,840) found no significant difference in efficacy (reduction in risk of major cardiovascular adverse events, myocardial infarction, and stent thrombosis) or safety (major bleeding) for the use of P2Y12 inhibitors in men and women.
The Lancet Haematology
Danish cohort study (n=4,679 propensity matched patients) found lower rates of recurrent VTE at 6 months for rivaroxaban compared to warfarin (9.9 incidents per 100 person-years vs 13.1 HR 0.74, 95%CI 0.56-0.96). Bleeding rates were similar.
Journal of Vascular Surgery
Study (n=9179) found perioperative clopidogrel (vs. non use) in lower extremity bypass surgery is linked to increased blood loss (21% vs 12%; p<0.001) and blood transfusion (38% vs 24%; p<0.001), with associated clinical sequelae of increased cardiac and pulmonary complications.
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 3rd April 2017
Journal of the American College of Cardiology
Meta-analysis of 4 RCTs noted that in this population without moderate/severe mitral stenosis/mechanical heart valves, NOACs seem attractive alternatives to vitamin K antagonists because coexistence of valvular heart disease does not affect overall relative efficacy/safety.
Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes
Heart
Paper reports that long-term bleeding risk during dual antiplatelet therapy (DAPT) for patients with ACS can be reliably predicted with selected baseline characteristics using TRILOGY ACS bleeding risk models thus informing risk–benefit considerations regarding DAPT duration.
Stability of repackaged dabigatran etexilate capsules in dose administration aids
European Journal of Hospital Pharmacy
Study reports storage of capsules at ambient conditions for 14 and 28 days resulted in % drug remaining of 92.5% and 71.6%, respectively. In contrast, repackaged capsules stored in fridge for 28 days had drug content of 98.2% and dissolution was not significantly affected.
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Anticoagulation news items. Week commencing 20th March 2017
European Heart Journal
Data from observational cohort studies suggest beneficial effect of statin on venous thromboembolism recurrence. In pooled analysis of 7 trials, relative risk (RR) was 0.73 (0.68–0.79) vs. no use. RRs for recurrent PE and DVT were 0.75(0.58–0.96) and 0.66 (0.60–0.71) respectively.
Biospace Inc.
Recombinant ADAMTS13 is intended for treatment of acute episodes of hereditary thrombotic thrombocytopenic purpura in patients with a constitutional deficiency of the von Willebrand factor-cleaving protease ADAMTS13. Shire is initiating open-label, 2-period crossover RCT.
Should we screen extensively for cancer after unprovoked venous thrombosis?
British Medical Journal
Prevalence of occult cancer in patients with 1st unprovoked venous thromboembolism seems to be lower (~4%) than previously reported (10%). Review notes high quality data from recently completed trials suggest no additional value for extensive screening strategies.
British Journal of Clinical Pharmacology
Real-life cohort study (n=30146) suggests risk of acute myocardial infarction was doubled with direct oral anticoagulants or aspirin vs. vitamin k antagonists (HR 2.11; 95% CI 1.08 – 4.12 and 1.91; 1.45-2.51, respectively). Further research from is required.
Two Paradigms for Endovascular Thrombectomy After Intravenous Thrombolysis for Acute Ischemic Stroke
JAMA Neurology
French study of 159 patients ultimately treated by mechanical thrombectomy, of which 100 received IV thrombolysis before transport to a more fully equipped hospital, and 59 did not, found no difference in functional independence at 3 months after stroke between the 2 groups.
Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism
New England Journal of Medicine
RCT of 3365 patients randomised after 6-12months anticoagulant therapy found symptomatic recurrent fatal/nonfatal venous thromboembolism occurred in 1.5% patients given 20 mg and 1.2% given 10 mg rivaroxaban, vs. 4.4% given aspirin (p<0.001 vs. aspirin for both).
British Medical Journal
This validation study (n= 2785) of the HERDOO2 clinical assessment tool found that women with 0 or 1 of the 4 criteria have a low risk of recurrent venous thromboembolism and can safely discontinue anticoagulants after completing short term treatment.
Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation
New England Journal of Medicine
The RE-CIRCUIT trial (n= 704) found that the incidence of major bleeding events after ablation was lower with dabigatran versus warfarin in patients with atrial fibrillation (1.6% vs 6.9%; absolute risk difference, −5.3%; 95% CI, −8.4 to −2.2; P<0.001).
The Lancet
RCT (n= 3,037) found that low-dose rivaroxaban with a P2Y12 inhibitor (clopidogrel or ticagrelor) had a similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes (5% both groups).
The Lancet
Registry data analysis found that leaflet thrombosis was less frequently observed in patients using warfarin or novel oral anticoagulants (eight [4%] of 224) than in those using dual antiplatelet or monoantiplatelet therapy (98 [15%] of 666; p<0•0001).
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 13th March 2017
Interruption to antiplatelet therapy early after acute ischaemic stroke: A nested case-control study
British Journal of Clinical Pharmacology
Study of 194 cases and 776 matched controls, of whom 10 and 58, respectively, stopped/interrupted antiplatelets found no significant link between interrupted/cessation of use and risk of CV events, though study had limited power and clinically important risk cannot be excluded.
Circulation
Several RCTs have been published since 2014 guideline. Major areas of change include indications for transcatheter aortic valve replacement, surgical management of primary/secondary mitral regurgitation, and management of patients with valve prostheses.
Thrombosis and Haemostasis
Review of 4 RCTs (n=28,105) found that extended thromboprophylaxis was associated with a lower risk of DVT though PE and VTE related mortality differences were not significant. The NNT for DVT prevention was 339, with a NNH for major bleed as 247.
Journal of the American Medical Association
A study of 94,474 patients with acute ischemic stroke and AF found that 84% did not receive guideline-recommended therapeutic anticoagulation preceding the stroke. Therapeutic anticoagulation was associated with lesser stroke severity and lower odds of in-hospital mortality.
Cochrane Database of Systematic Reviews
Moderate-level data suggest that fixed dose LMWH reduced incidence of recurrent thrombotic complications and occurrence of major haemorrhage during initial treatment; and low-quality data suggest fixed dose LMWH reduced thrombus size vs UFH for the initial treatment of VTE.
Early non-persistence with dabigatran and rivaroxaban in patients with atrial fibrillation
Heart
Study (n=25,976) found at 6 months, 36.4 and 31.9% of patients were non-persistent to dabigatran and rivaroxaban, respectively. Stroke/TIA/death was higher with non-persistence vs. persistence (HR 1.76, 95% CI 1.60-1.94 and 1.89, 1.64-2.19; p<0.0001 for both, 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:
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Anticoagulation news items. Week commencing 6th March 2017
Subcutaneous unfractionated heparin for the initial treatment of venous thromboembolism
Cochrane Database of Systematic Reviews
This review of 16 RCTs (n=3593; general low quality) concludes that there is no evidence of a difference between subcutaneous unfractionated heparin (UFH) and intravenous UFH or subcutaneous low molecular weight heparin for preventing recurrent clots, mortality or major bleeding.
National Institute for Health Research
NOACs have advantages over warfarin in AF patients, but there was no strong evidence they should replace warfarin/low molecular weight heparin in primary prevention (PV), treatment or secondary PV of venous thromboembolism. Findings limited by lack of head to head NOAC studies.
The Lancet
This paper describes PRECISE-DAPT score, a simple 5-item risk score (age, creatinine clearance, haemoglobin, white-blood-cell count, previous spontaneous bleeding), which provides a standardised tool for prediction of out-of-hospital bleeding during dual antiplatelet therapy.
European Heart Journal
Review highlights that when compared with earlier systematic review, increased use of mechanical valves with lower thrombogenic potential has not necessarily resulted in lower risk of adverse outcomes, and optimal method of anticoagulation remains undetermined in this population.
Journal of Thrombosis and Haemastasis
Relative to low-molecular-weight heparin, direct oral Xa inhibitors had a more favorable profile of venous thromboembolism and haemorrhage risk, whereas vitamin K antagonists had a less favorable profile. The profile of other agents was not more or less favourable.
British Journal of Clinical Pharmacology
Analysis of 6 Roux-en-Y gastric bypass and 6 sleeve gastrectomy patients found bariatric surgery does not appear to alter pharmacokinetics of rivaroxaban in clinically relevant way. Effective prophylactic postbariatric anticoagulation is supported by changes in pharmacodynamics.
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Anticoagulation news items. Weeks commencing 27th February 2017
European Heart Journal
This modelling study was developed from data taken from UK population-based electronic health records (n=12694 and 5613, respectively), and quantified the potential benefits and harms of prolonged dual antiplatelet therapy (DAPT) in MI survivors.
Duration of dual antiplatelet therapy in acute coronary syndrome
Heart
Review notes it has been 15 years since CURE trial showed benefit of dual antiplatelet therapy following ACS and yet optimal duration remains uncertain. It highlights need for broad inclusive safety trial of shorter durations of therapy in real world populations of ACS patients.
Association of Antithrombotic Drug Use With Subdural Hematoma Risk
Journal of the American Medical Association
Study (10,010 patients, 400,380 controls) found antithrombotic use increased risk of subdural haematoma. Highest odds were associated with combined use of vitamin K antagonist+antiplatelet (aspirin or clopidogrel, OR 4.00, 95%CI 3.40-4.70, and 7.93, 4.49-14.02, 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:
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Anticoagulation news items. Weeks commencing 20th February 2017
Circulation
Among 11,648 randomised patients, monthly cumulative incidence of MI was lower with continued thienopyridine vs. placebo at 12-15 months (0.12% vs. 0.37%, p<0.001) and higher at 30-33 months (0.30% vs. 0.15%, p=0.013). Majority of MIs were not related to stent thrombosis.
Thrombosis and Haemostasis
Spanish registry study (n=1725) noted patients on DOACs at non-recommended doses and/or regimens experienced higher rate of venous thromboembolism recurrences (HR:10.5;95 %CI:1.28–85.9) and similar rate of major bleeding/death vs. those on recommended doses and regimens.
Journal of the American Medical Association
RCT (n=120) found among patients with intraoperative bleeding during high-risk cardiac surgery, administration of IV single dose fibrinogen concentrate, vs.
placebo, resulted in no significant difference in the amount of intraoperative blood loss (50 vs. 70mL, respectively).
electronic Medicines Compendium
FibCLOT is licensed for the treatment and perioperative prophylaxis of bleeding in patients with congenital hypo- or afibrinogenaemia with bleeding tendency.
JAMA Internal Medicine
Study of 2415 patients who experienced a traumatic intracranial haemorrhage (ICH) or haemorrhagic stroke (HS) showed resuming warfarin therapy was associated with lower rate of ischaemic stroke or systemic embolism. However, in those with HS, a high rate of ICH was observed.
Effects of dabigatran according to age in atrial fibrillation
Heart
Analysis (n=10855) found effects of dabigatran vs. warfarin on stroke prevention/intracranial bleeding were consistent across all ages. Effects of dabigatran on extracranial major bleeding were age dependent, supporting use of 110 mg BD dose for elderly patients (≥80 years).
Drug-induced liver injury (DILI) with oral anticoagulants: a threat or not?
Heart
This editorial discusses the background of DILI, highlighting that it can develop with the use of nearly any drug. It then goes on to discuss the current
evidence base for DILI with oral anticoagulants, reviewing the use of the newer drugs in liver impairment vs. warfarin.
Anticoagulation news items. Weeks commencing 13th February 2017
British Journal of Clinical Pharmacology
Retrospective cohort study (n=31,497) found NOACs and vitamin K antagonists equally effective in preventing stroke but NOACs were linked to higher risk of GI bleeding (HR 2.63, 95% CI 1.50-4.62), particularly in women. Aspirin was not effective in prevention of stroke in AF.
Circulation
191 patients in ENGAGE AF-TIMI 48 trial had bioprosthetic valves, of which those on higher-dose edoxaban (HDED) had similar rates of stroke/ systemic embolic events (S/SEE) and major bleeding (MB) vs warfarin. Patients on lower DED had similar rates of S/SEE but lower rates of MB.
European Heart Journal
This covers diagnosis, initial (first 5–21 days) and long-term (first 3–6 months) phase management, extended phase management (beyond first 3–6 months), and special situations.
Journal of the American Medical Association
Review notes that despite limitations of observational data about NOAC use for stroke prevention in AF, they do broadly confirm results of the pivotal NOAC
RCTs and show that these agents are viable alternatives to warfarin in routine clinical practice.
The Lancet Haematology
Study (n=435) reports primary outcome (composite of symptomatic DVT or PE, progression or recurrence of superficial vein-thrombosis, and all-cause
mortality at 45 days) occurred in 3% of those on rivaroxaban v 2% of those on fondaparinux (HR 1.9, p=0·0025 for non-inferiority).
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