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).
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 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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Anticoagulation news items. Weeks commencing 19th December 2016
Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal
Thrombosis and Haemostasis
Review found prothrombin complex concentrate (PCC) normalises INR more often and faster than fresh frozen plasma in warfarin-treated patients with major
bleeding/need for urgent surgery/ invasive procedure. PCCs were also less likely to cause volume overload or heart failure.
NIHR Signal: Long-haul flyers could reduce risk of leg blood clots with compression stockings
National Institute for Health Research Signal
This is an expert commentary of a Cochrane review which found that airline passengers could reduce their risk of getting a deep vein thrombosis by wearing
compression stockings, even if they are at low risk.
NIHR Signal: People prefer shorter compression stockings to prevent blood clots
National Institute for Health Research Signal
This is an expert commentary of a systematic review which found people having surgery prefer wearing knee length to thigh length compression stockings to prevent deep vein thrombosis, and are more likely to wear knee length stockings correctly and for the recommended time.
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 12th December 2016
BMJ Open
Semi-structured interviews with 31 patients requiring venous thromboembolism (VTE) prophylaxis following recent hospital admission in UK found good adherence to heparin and poor adherence to elastic compression stockings, as well as limited knowledge of signs and symptoms of VTE.
BMJ Open
Analysis of data on 3566 adults from 33 A+Es found CT scanning for all anticoagulated patients with head injury is not cost-effective (£94,895/QALY gained) vs. selective scanning based on guidelines recommending scanning only for those with evidence of traumatic brain injury.
Thrombus Aspiration in ST Elevation Myocardial Infarction: An Individual Patient Meta-analysis
Circulation
Review of 3 RCTs (n=19,047) found no difference in CV death at 30 days for thrombus aspiration plus PCI vs PCI alone, however in those with high thrombus burden (TIMI thrombus grade ≥3) thrombus aspiration was associated with less CV death (2.5% vs 3.1%, HR 0.80; 95%CI 0.65-0.98).
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 December 2016
Pentasaccharides for the prevention of venous thromboembolism
Cochrane Database of Systematic Reviews
Review (n=21004) found moderate to high quality evidence that fondaparinux is effective for short term prevention of VTE vs. placebo. Low to moderate quality evidence shows that fondaparinux is effective for short-term prevention of VTE vs. low molecular weight heparin.
A Critical Appraisal of Aspirin in Secondary Prevention: Is Less More?
Circulation
This article critically reviews the available evidence for aspirin use after ACS and PCI and discusses the scientific rational for ongoing studies testing the risks and benefits of omission or early discontinuation of aspirin in favor of P2Y12 inhibitor monotherapy.
British Medical Journal
This cohort study based on 433 353 deliveries in England and 662 387 in Sweden has been used to develop a new prediction model that quantifies absolute risk of postpartum VTE based on clinical variables in order to serve as the basis for decisions on obstetric thromboprophylaxis.
Cochrane Database of Systematic Reviews
Moderate quality evidence suggests that combining IPC and pharmacological prophylaxis, compared with either alone, decreases the incidence of DVT when compared to compression, and incidence of PE when compared to anticoagulation.
Thromboprophylaxis after Knee Arthroscopy and Lower-Leg Casting
New England Journal of Medicine
Two open label RCTs (n=1,543; n=1,519) found no significant difference in the rate of VTE for 8 days prophylactic LMWH vs no thromboprophylaxis post arthroscopy or prophylactic LMWH or no thromboprophylaxis after cast treatment.
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Anticoagulation news items. Weeks commencing 28th November 2016
Compression stockings for preventing deep vein thrombosis in airline passengers
Cochrane Database of Systematic Reviews
Review found high-quality evidence that airline passengers can expect a substantial reduction in the incidence of symptomless DVT and low-quality evidence that leg oedema is reduced if passengers wear compression stockings.
Antiplatelet versus anticoagulation treatment for patients with heart failure in sinus rhythm
Cochrane Database of Systematic Reviews
Evidence suggests neither anticoagulation (warfarin) nor antiplatelet therapy (aspirin) is better for mortality in systolic heart failure with sinus rhythm
(high quality evidence for all-cause mortality, moderate quality evidence for non-fatal CV and major bleeding events).
Testosterone treatment and risk of venous thromboembolism: population based case-control study
British Medical Journal
UK study (n=19 215 DVT/PE; 909,530 age matched controls) found starting testosterone linked to increased venous thromboembolism risk which peaked within 6 months (rate ratio 1.63; 95% CI, 1.12-2.37 corresponding to 10 additional cases above base rate) and declined thereafter.
Hormonal Contraception and Risk of Thromboembolism in Women With Diabetes
Diabetes Care
Study (146,080 women, 3,012 thromboembolic events) found rates of thromboembolism were highest among women on the contraceptive patch (16 per 1,000 woman-years) and lowest with intrauterine (6 per 1,000 woman-years) and subdermal (0 per 163 woman-years) contraceptives.
Optimal duration of dual antiplatelet therapy after acute coronary syndromes and coronary stenting
Heart
This article provides an overview of the evidence, current guidelines' recommendations and future perspectives on dual antiplatelet therapy (DAPT)
duration after an ACS and after coronary stenting. It proposes an algorithm of optimal duration of DAPT in these settings.
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