Thrombolytic therapy for pulmonary embolism

Cochrane Database of Systematic Reviews

Review of 18 RCTs (n=2197) concludes low‐quality evidence shows thrombolytics in addition to heparin reduce death and recurrence of pulmonary embolus following acute pulmonary embolism, compared with heparin alone. The included studies used a variety of thrombolytic drugs.


Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases

British Medical Journal

Analysis (n=80 396 matched to 391,494 controls.) found most oral preparations were linked to increased VTE risks. Conjugated equine oestrogens with or without medroxyprogesterone acetate, were linked to highest risks. No increased risk was found for transdermal preparations.


Relationship between body mass index and outcomes in patients with atrial fibrillation treated with edoxaban or warfarin in the ENGAGE AF-TIMI 48 trial

European Heart Journal

Review of data from the ENGAGE AF-TIMI 48 trial found that an increased BMI was independently associated with a lower risk of stroke or systemic embolic events (per 5 kg/m2 increase, HR=0.88, p=0.0001), but increased risk of major bleeding (HR 1.06, P = 0.025).


Inhaled Tranexamic Acid for Hemoptysis Treatment


RCT (n=47) found that resolution of hemoptysis within 5 days of admission was observed in more tranexamic acid (TXA) treated vs placebo (96% vs 50%; p< 0.0005). TXA patients also had a shorter hospital stay and required fewer interventional procedures.


Effect of Low-Dose Intracoronary Alteplase During Primary Percutaneous Coronary Intervention on Microvascular Obstruction in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial

Journal of the American Medical Association

RCT (n=195) was stopped early due to futility. Among patients with acute STEMI presenting within 6 hours of symptoms, adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction vs placebo.


Pro‐coagulant haemostatic factors for the prevention and treatment of bleeding in people without haemophilia

Cochrane Database of Systematic Reviews

Review of 31 RCTs (n=2392) found that paucity of good‐quality evidence precludes the drawing of conclusions for clinical practice. Sample sizes of future RCTs would need to be greatly increased to detect a reduction in mortality or thromboembolic events between treatment arms.


Uterotonic agents for preventing postpartum haemorrhage: a network meta‐analysis

Cochrane Database of Systematic Reviews

Analysis (196 trials; n=135,559; 7 uterotonic agents) found all agents were generally effective vs. placebo or no treatment. Some oxytocin (OX) combination regimens may have some additional desirable effects vs current standard OX but are linked to significant side effects.


Tranexamic acid for patients with nasal haemorrhage (epistaxis)

Cochrane Database of Systematic Reviews

Review of 6 RCTs (n=692) found moderate‐quality evidence that there is probably a reduction in the risk of re‐bleeding with use of either oral or topical tranexamic acid in addition to usual care in adults with epistaxis, compared to placebo with usual care.


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NIHR Signal: People leaving hospital after medical illness do not benefit from extended clot reducing treatment

National Institute for Health Research Signal

Commentary is provided of trial which found continued use of rivaroxaban offered very small reduction in VTE risk, but also slightly increased risk of major bleeding (neither statistically significant). Trial was terminated because of lower than expected number of clots.


Efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a meta-analysis of randomized controlled trials

European Heart Journal

Data from phase 3 trials found that, irrespective of direct oral anticoagulant (DOAC) used, rates of stroke or systemic embolism and major bleeding were higher in those eligible for reduced-dose DOACs than in those eligible for full-dose DOACs (2.70% vs 1.60% and 4.35% vs 2.87%).


When is it appropriate to stop non-vitamin K antagonist oral anticoagulants before catheter ablation of atrial fibrillation? A multicentre prospective randomized study

European Heart Journal

Open label RCT (n=326) found a higher intra-procedural heparin requirement with 24-hour skipped DOACs vs single dose skipped and uninterrupted regimens (p<0.001) though the incidence of major bleeding up to 1 month after ablation did not differ.


Association of Parenteral Anticoagulation Therapy With Outcomes in Chinese Patients Undergoing Percutaneous Coronary Intervention for Non–ST-Segment Elevation Acute Coronary Syndrome

JAMA Internal Medicine

Chinese cohort study (n=6,804) found that parenteral anticoagulant therapy did not reduce the incidence of in-hospital death, or rate of myocardial infarction vs those that did not receive it. Bleeding was more frequent with anticoagulation (2.5% vs 1.0%, p<0.001).


Human coagulation factor X for hereditary factor X deficiency (all ages)

NHS England

NHS England will not routinely commission human coagulation factor X for people of all ages with hereditary factor X deficiency who need long term prophylaxis owing to insufficient published evidence.




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Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis

British Medical Journal

Review of 3 RCTs (n=10,447) found that compared with aspirin alone clopidogrel plus aspirin, started within 24 hours of symptom onset, reduced the risk of non-fatal recurrent stroke (RR 0.70, 95% CI 0.61-0.80, absolute risk reduction 1.9%).


Graduated compression stockings for prevention of deep vein thrombosis

Cochrane Database of Systematic Reviews

Review of data from 20 high-quality RCTs (n=1681) concludes graduated compression stockings are effective in reducing the risk of DVT in hospitalised patients who have undergone general and orthopaedic surgery, with or without other methods of background thromboprophylaxis.


Rutosides for treatment of post‐thrombotic syndrome

Cochrane Database of Systematic Reviews

Review of 3 low quality RCTs (n=233) concludes rutosides are not superior to placebo or elastic compression stockings for post‐thrombotic syndrome, characterised by pain, swelling, and skin changes in affected limb. Rutosides are a group of compounds derived from horse chestnut.


NIHR Signal: The best dose of aspirin for cardiovascular protection may depend on body weight

National Institute for Health Research Signal

Expert commentary is provided for a review of 13 RCTs which found that low dose aspirin was effective for secondary prevention in those <70kg, but not >70kg. The findings reinforce the importance of tailoring the aspirin dose to a patient's characteristics, including weight.


Efficacy and safety of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials

European Heart Journal

Analysis of 11 trials (n=157,248) found at mean follow-up of 6.6 years, aspirin was not linked to lower incidence of all-cause mortality but to increased incidence of major bleeding (RR 1.47, 95% CI 1.31–1.65; p< 0.0001) and intracranial haemorrhage (1.33, 1.13–1.58; p = 0.001).


Janssen submits supplemental new drug application to US FDA for rivaroxaban to prevent venous thromboembolism in acute medically ill patients

Biospace Inc.

Application is based on data from phase 3 MAGELLAN and MARINER trials. MAGELLAN met its co-primary endpoints, demonstrating non-inferiority to enoxaparin in short-term (10 days) and superiority in long-term (35 days) use, while MARINER demonstrated reduction in symptomatic VTE.


Effectiveness and safety of 110 or 150 mg dabigatran vs. vitamin K antagonists in nonvalvular atrial fibrillation

British Journal of Clinical Pharmacology

French new-users cohort study (n=14,442) reported that dabigatran at either dose was associated with less major bleeding, stroke and systemic embolism and all-cause mortality than matched VKA-treated patients.


Effectiveness and safety of apixaban versus rivaroxaban for prevention of recurrent venous thromboembolism and adverse bleeding events in patients with venous thromboembolism: a retrospective population-based cohort analysis

The Lancet

US database study (3091 apixaban users and 12,163 rivaroxaban users) reported that use of apixaban vs rivaroxaban was associated with decreased risk of recurrent VTE (HR 0.37; 95% CI 0.24–0.55]; p<0.0001) and major bleeding events (0.54; 0.37–0.82; p=0.0031).


MI risk associated with naproxen and diclofenac in spondyloarthritis: DTB Select summary

Drug and Therapeutics Bulletin

Summary and context is provided for analysis of the incidence of myocardial infarction in people with spondylarthritis and osteoarthritis treated with NSAIDs which provides further evidence that diclofenac is associated with a higher risk than naproxen.


Comparative safety and effectiveness of direct oral anticoagulants in patients with atrial fibrillation in clinical practice in Scotland

British Journal of Clinical Pharmacology

Retrospective cohort study (n=14,577) found all DOACs were similarly effective in preventing stroke, systemic embolism or CV death, while patients on rivaroxaban showed highest bleeding risks.Observed differences in risks of all‐cause mortality, MI and PE warrant further research.



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:




In use product safety assessment report for enoxaparin biosimilars (INHIXA and AROVI)

Specialist Pharmacy Service

This assessment on Inhixa and Arovi (enoxaparin biosimilars) describes the in-use medication safety considerations resultant from the products' presentation or other pre-defined characteristics. Potential next steps and mitigation actions are suggested.


Cyclin-Dependent Kinase Inhibitor–Associated Thromboembolism

JAMA Oncology

An overview of the evidence that this drug class (of which palbociclib is the first in class) is associated with an increased incidence of thromboembolism. NICE support the use of palbociclib for use within its marketing authorisation.



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Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

Cochrane Database of Systematic Reviews

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 after major abdominal or pelvic surgery.


Major Bleeding Rates in Atrial Fibrillation Patients on Single, Dual, or Triple Antithrombotic Therapy: Results from a Nationwide Danish Cohort Study


Study (n=272,315) found triple therapy linked to high rates of major bleeding vs. dual or monotherapy. Very high major bleeding rates occurred among patients on triple therapy aged > 90 years or with CHA2DS2-VASc > 6 or with a history of major bleeding.


Association of Oral Anticoagulants and Proton Pump Inhibitor Co-therapy With Hospitalization for Upper Gastrointestinal Tract Bleeding

Journal of the American Medical Association

Retrospective study found during 754,389 person-years of anticoagulation with apixaban, dabigatran, rivaroxaban [RV], and warfarin, risk of hospitalisation for upper GI bleeding was highest for RV. PPI cotherapy (264,447 person-years) was linked to lower overall GI bleeding risk.


Apixaban to Prevent Venous Thromboembolism in Patients with Cancer

New England Journal of Medicine

RCT (n=574) found apixaban (2.5mg BD) resulted in lower rate of venous thromboembolism vs. placebo in intermediate/high-risk ambulatory patients with cancer starting chemo (12 [4.2%] vs. 28 [10.2%]; HR 0.41; 95% CI, 0.26-0.65; p<0.001) but higher rates of major bleeding episodes.


Conference report: positive results for emicizumab for paediatric haemophilia A

Biospace Inc.

Primary analysis of the HAVEN 2 study (n=85) has found that once-weekly emicizumab dosing showed a 99% reduction in treated bleeds compared to prior treatment with bypassing agents.



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Early Risks of Death, Stroke/Systemic Embolism and Major Bleeding in Patients with Newly Diagnosed Atrial Fibrillation: Results from the GARFIELD-AF Registry


Registry study (n=52,014) found an elevated mortality rate in the first month after diagnosis vs the first year (6.8 vs 4.3 100 person years for first month and first year respectively). The elevated 1-month mortality rate was mostly attributable to cardiovascular mortality.


Subcutaneous treprostinil for the treatment of severe non-operable chronic thromboembolic pulmonary hypertension (CTREPH): a double-blind, phase 3, randomised controlled trial

The Lancet Respiratory Medicine

RCT (N=105) reported an improvement from baseline in mean 6-min walk distance in the treprostinil high and low dose groups (44·98 m and 4·29 m; p=0·0016). Treprostinil is an investigational prostacyclin analogue that has received orphan drug status in the EU.




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Efficacy and Safety of Drug-Eluting Stents Optimized for Biocompatibility vs Bare-Metal Stents With a Single Month of Dual Antiplatelet Therapy: A Meta-analysis

JAMA Cardiology

This review of 3 RCTs (n=3943) comparing bare-metal stents (BMSs) to drug-eluting stents (DESs) with shortened duration of dual antiplatelet therapy (one month only) found DES were associated with lower risk of major adverse cardiac events and other adverse outcomes.



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The role of plasminogen activators in stroke treatment: fibrinolysis and beyond

The Lancet Neurology

This review describes the pathophysiological effects of plasminogen activators and how, in the future, their non-fibrinolytic functions could be used for the treatment of patients with acute ischaemic and haemorrhagic stroke.


Practice guide to dosing of direct acting oral anticoagulants in patients with renal impairment

Specialist Pharmacy Service

This paper, focusing on use of DOACs in patients with atrial fibrillation, discusses the debate regarding the dosing of DOACs in patients with renal impairment and offers some practical advice on selecting the dose in the clinical setting.


Management of life threatening bleeds from arteriovenous fistulae and grafts

NHS Improvement

Alert signposts providers to resources produced jointly by British Renal Society and Vascular Access Society of Britain and Ireland to help staff, carers and patients recognise warning signs. Providers are asked to ensure local guidance incorporates advice in these resources.


Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke

Cochrane Database of Systematic Reviews

Review (4 trials, n=450) found no RCT evidence that percutaneous vascular interventions are superior to intravenous thrombolytic treatment with respect to functional outcome. Quality of evidence was low (outcome assessment was blinded but not treating physician/participants).


Performance of the ABC Scores for Assessing the Risk of Stroke or Systemic Embolism and Bleeding in Patients with Atrial Fibrillation in ENGAGE AF-TIMI 48


Paper reports that ABC-stroke and ABC-bleeding risk scores which comprise clinical variables and CV biomarkers to estimate risk of stroke/systemic embolic events and bleeding, respectively, were well-calibrated and outperformed the CHA2DS2-VASc and HAS-BLED scores, respectively.


Self‐poisoning with 60 tablets of Apixaban, a pharmacokinetics case report

British Journal of Clinical Pharmacology
Apixaban was eliminated following first order elimination with a calculated half‐life of 10.8 h. Anti‐Xa activity seems to be linearly related to concentration up to 4000 μg/ l. This report suggests use of activated charcoal should be effective up to 17 h after a massive intake.




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Barriers to a software reminder system for risk assessment of stroke in atrial fibrillation: a process evaluation of a cluster randomised trial in general practice

British Journal of General Practice

An evaluation of 23 practices found that an automated risk assessment for stroke in AF and prompting during consultations are feasible and generally acceptable, but did not overcome concerns about frailty and risk of haemorrhage as barriers to anticoagulant uptake.


Revised SPCs: Plavix (clopidogrel) 75 and 300mg tablets

electronic Medicines compendium

Insulin autoimmune syndrome has been added to SPCs as an adverse effect (unknown frequency). This can lead to severe hypoglycaemia, particularly in patients with HLA DRA4 subtype (more frequent in the Japanese population).


Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation

The Lancet Neurology

This Rapid Review summarises and critically reviews current guidelines and new published data, and gives an overview of ongoing investigator-initiated randomised controlled trials of oral anticoagulation timing after ischaemic stroke associated with atrial fibrillation.



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Impact of anticoagulant choice on hospitalized bleeding risk when treating cancer-associated venous thromboembolism

Journal of Thrombosis and Haemastasis

This US retrospective study (26,894 people with cancer-associated venous thrombosis), found that the bleeding risk with DOACs was similar to warfarin and low molecular weight heparin. There was however heterogeneity in bleeding risk with DOACs by cancer type.


Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation: A Systematic Review

Annals of Internal Medicine

Review of 220 articles aimed to compare the effectiveness of medical and procedural therapies in preventing thromboembolic events and bleeding complications in adults with non-valvular AF. It found DOACs are at least as effective and safe as warfarin for patients.


Idarucizumab for Dabigatran Reversal in the Management of Patients with Major Gastrointestinal Bleeding


In RE-VERSE AD trial, idarucizumab showed rapid/complete reversal of dabigatran activity in nearly all patients with GI bleeding; complete reversal in 118 of 121 (97.5%) with elevated diluted thrombin time at presentation and 95 of 131 (72.5%) with elevated ecarin clotting time.


Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome


Trial (n=120) was terminated early due to an excess of events in the rivaroxaban group compared to warfarin (7 thromboembolic events; 4 ischemic stroke and 3 myocardial infarction vs. 0 events, respectively). Major bleeding occurred in 4 vs. 2 patients, respectively.



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