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).
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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).
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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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Anticoagulation news items. Weeks commencing 6th February 2017
Circulation
This statement reviews the literature and offers practical suggestions for providers who manage patients who are actively bleeding and who are at risk
for bleeding in the acute care and periprocedural setting.
Peri-Operative Management of Anticoagulation and Antiplatelet Therapy
British Society for Haematology
This guideline will consider whether and when anticoagulants and antiplatelet agents should be stopped before elective surgery and invasive procedures,
when agents can be restarted and how to manage patients on these drugs who require emergency surgery.
British Medical Journal
Study (n=55,644) found no significant difference (SD) vs. warfarin (WF) in ischaemic stroke/systemic embolism rates with apixaban (AP) 2.5mg or in
thromboembolic rates with dabigatran (DB) 110mg and rivaroxaban (RV) 15mg. There was no SD in bleeding rates between AP and RV vs. WF
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Anticoagulation news items. Weeks commencing 23rd January 2017
European Heart Journal
Analysis of registry data on 42,887 ischaemic stroke patients (251 on NOACs; 1500 on warfarin before stroke) treated with intravenous rt-PA within 4.5 hours found no significant difference in symptomatic intracranial haemorrhage in anticoagulated(AC'd) vs. non-AC'd patients.
Gastroenterology
RCT (n=270) found lower proportion of patients on PPI developed recurrent upper GI bleeding (0.7 v 3.1%) and reached composite end point of recurrent
bleeding/endoscopic ulcers at month 12 (7.9 vs. 12.4%) vs. H2 antagonist group, but difference was not statistically significant.
Annals of Surgery
This analysis of 13 studies (n=14,776) concludes benefit of peri-operative VTE chemoprophylaxis was only found among surgical patients with Caprini scores
≥7. Patients with scores ≤6 comprised 75% of overall population and did not show a VTE risk reduction with chemoprophylaxis.
Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy
Cochrane Database of Systematic Reviews
This updated review confirms that primary thromboprophylaxis with low molecular weight heparins significantly reduces the incidence of symptomatic venous
thromboembolism in ambulatory cancer patients treated with chemotherapy.
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Anticoagulation news items. Weeks commencing 16th January 2017
Revised SPC: Dipyridamole 50mg/5ml Oral Suspension
electronic Medicines Compendium
Angina pectoris, post procedural haemorrhage and operative haemorrhage have been added as adverse reactions of dipyridamole.
Revised SPC: Nebido (testosterone undecanoate) 1000mg/4ml, solution for injection
electronic Medicines Compendium
Section 4.4 of SPC now includes warning that testosterone should be used with caution in patients with thrombophilia, as there have been post-marketing studies and reports of thrombotic events in these patients during testosterone therapy.
Medicines and Healthcare products Regulatory Agency
It is advised that INR should be monitored closely during treatment of chronic hepatitis C with direct-acting antivirals in patients also receiving vitamin
K antagonists (e.g. warfarin), because of possible changes in liver function during treatment.
Incidence of venous thromboembolism in care homes: a prospective cohort study
British Journal of General Practice
During a mean follow-up period of 312 days, this observational cohort study (n=1011) reports an increased incidence of venous thromboembolism in care homes compared to the community setting in people aged over 70 years.
Valvular heart disease and pregnancy part II: management of prosthetic valves
Heart
This is a review of 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 9th January 2017
JAMA Cardiology
Research letter-reports on study (n=734) which showed high rate of discontinuation of warfarin within first year (36.8%), especially among patients undergoing electrical cardioversion or radiofrequency ablation (54.1% vs.29.5% not undergoing these procedures; p<0.001).
Antifibrinolytic therapy to reduce haemoptysis from any cause
Cochrane Database of Systematic Reviews
There is insufficient evidence to judge whether antifibrinolytics should be used to treat haemoptysis from any cause, though limited evidence suggests they may reduce the duration of bleeding.
British Journal of Clinical Pharmacology
This analysis of 32,972 reports of adverse events (from WHO VigiBase database) shows increased risk of gastrointestinal haemorrhage in patients treated with
direct oral anticoagulants vs warfarin (OR 1.6, p≤0.05), and a reduced risk of intracranial haemorrhage (OR 0.31, p≤0.05).
Heparin for the treatment of thrombosis in neonates
Cochrane Database of Systematic Reviews
No studies were identified that met the inclusion criteria for this evaluation, and therefore no recommendations can be made for the use of heparin for the
treatment of neonates with thrombosis.
European Heart Journal
This paper describes development of a risk score (TIMI-AF) using data from ENGAGE AF-TIMI 48 trial (edoxaban vs. warfarin) to identify vitamin K antagonist
(VKA) naive patients for whom a therapeutic benefit of non-vitamin K antagonist oral anticoagulants over a VKA is predicted.
Heart
Analysis (n=113,717 with AF, mean age 70, 39% women) found that over median 12 months follow-up, there were 960 hospitalisations with liver injury with rates for following anticoagulants: 9 (warfarin), 4.0 (dabigatran), 6.6 (rivaroxaban) and 5.6 (apixaban), per 1000 person-years.
JAMA Neurology
Analysis (n=291) found that treatment of patients experiencing acute ischaemic stroke due to a large vessel occlusion with intravenous thrombolysis before
mechanical thrombectomy (MT) did not appear to provide a clinical benefit over MT alone.
The Lancet
RCT (n=500) found in patients with intraventricular haemorrhage and routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes (modified Rankin Scale score ≤3 at 180 days) compared with irrigation with saline, but seems safe.
Biospace Inc.
Afstyla, the first and only single-chain product, is approved for treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor
VIII deficiency) in all age groups. It is specifically designed for protection from bleeds with 2 or 3 times weekly dosing.
Biospace Inc.
The pivotal phase 3 trial supporting licence application for this new treatment for patients with haemophilia A and B tested two initial dose regimens in 468
bleeding events occurring in 27 inhibitor patients. Both study arms met the primary end point of haemostatic success.
Heart
Review notes clinicians who initiate vitamin K antagonists in this group should expect substantial lability in anticoagulant activity and pursue an aggressive monitoring strategy; use of DOACs in moderate renal impairment pose theoretical risks and lack safety data in dialysis.
Statins and primary prevention of venous thromboembolism: a systematic review and meta-analysis
The Lancet Haematology
Review of 13 cohort studies and 23 RCTs (total n=3,266,723) found a pooled RR for VTE of 0.75 (95% CI 0.65-0.87) for cohort studies and 0.85 (0.73-0.99) for RCTs for statin vs placebo or no treatment. Rosuvastatin had the lowest risk vs other statins (RR 0.57, 0.42-0.75).
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Anticoagulation news items. Weeks commencing 3rd January 2017
Thrombolysis for acute deep vein thrombosis
Cochrane Database of Systematic Reviews
Evidence suggests that systemic administration and catheter-directed thrombolysis have similar effectiveness. Strict eligibility criteria may be necessary to reduce the risk of bleeding complications, but may limit the applicability of this treatment.
Impact of an Interaction Between Clopidogrel and Selective Serotonin Reuptake Inhibitors
American Journal of Cardiology
Findings from large, population-based study in US suggest being treated with CYP2C19-inhibiting SSRI (fluoxetine/fluvoxamine) when initiating clopidogrel
may be linked to increased risk of ischaemic events (HR 1.12; 95% CI, 1.01-1.24) vs. those treated with noninhibiting SSRI.
BMJ Open
Analysis of 26 interviews noted variable provision of self-monitoring equipment caused resentment and there were worries about cost of test strips. However,
self-funding did mean that interviewees felt a sense of ownership and were determined to persevere to overcome problems.
electronic Medicines Compendium
Section 4.4 now advises that testosterone should be used with caution in patients with thrombophilia, as there have been post-marketing studies and reports of thrombotic events in these patients during testosterone therapy.
Biospace Inc.
Betrixaban is an oral, once-daily Factor Xa inhibitor anticoagulant, for extended-duration prophylaxis of venous thromboembolism (VTE) in acute
medically ill patients with risk factors for VTE. The application is based on data from the phase III APEX study.
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