Pharmacist-led virtual clinics to optimise anticoagulation in AF

Public Health England

Over a 12-month period, the programme reviewed over 1500 patients with AF not receiving anticoagulation, which resulted in an additional 1,200 patients being anticoagulated. The 2 CCGs (Lambeth and Southwark) have since seen a 25% reduction in the rate of AF-related 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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors

New England Journal of Medicine
Cohort study of 352 patients with acute major bleeding associated with the use of a factor Xa inhibitor, reported that andexanet reduced anti–factor Xa activity by 93% from baseline, and that 82% of patients achieved haemostatic efficacy at 12 hours.

 

Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial

The Lancet
RCT reported no change in functional status at 90 days with intensive (target systolic BP 130–140 mm Hg within 1 h) or guideline-recommended (target <180 mm Hg) BP lowering therapy over 72 h in 2227 alteplase-eligible patients with acute ischaemic 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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation

Circulation

This guideline updates the recommendations on anticoagulation, catheter ablation of atrial fibrillation (AF), management of AF complicating acute coronary syndrome, and includes new recommendations on device detection of AF and weight loss.

 

NIHR Signal: Warfarin and newer anticoagulants equally effective for long-term treatment of blood clots

National Institute for Health Research Signal

Expert commentary is provided for a review of 16 RCTs (n=22,396) which found that all oral anticoagulants regimens reduce the risk of recurrent VTE vs placebo. Ideal regimens for those at higher risk (e.g. thrombophilia), and >1 year treatment still require further investigation.

 

Additional GI bleeding risk with SSRIs in people with declining kidney function: DTB Select

Drug and Therapeutics Bulletin
Summary and context is provided for a cohort study which reported an increased risk of GI bleeding with SSRIs in patients with CKD. Clinicians are advised to review the risks and benefits of SSRIs in this population and consider the need for gastroprotection.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis

Journal of the American Medical Association

Review of 13 RCTs (n=164,225) found that aspirin use reduced a composite of CV mortality, non-fatal MI/stroke vs no aspirin (57.1 vs 61.4 /10,000 patient-years, HR 0.89, 95% CI 0.84-0.95, NNT 265), however aspirin had an increased risk of major bleeding (1.43, 1.30-1.56, NNH 210).

 

Stroke Outcomes in the Cardiovascular OutcoMes for People using Anticoagulation StrategieS (COMPASS) Trial

Circulation

RCT (n=27,395) found a reduced risk of strokes with rivaroxaban 2.5mg twice daily plus aspirin 100mg daily vs aspirin alone (0.9% per year vs 1.6% per year, HR 0.58, 95% CI 0.44-0.76). The effect of the combination compared with aspirin was consistent across subgroups.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

Revised SPCs: Efient (prasugrel) 5 mg 10 mg film-coated tablets

electronic Medicines compendium

SPCs have been updated to advise a delayed and decreased exposure to oral P2Y12 inhibitors, including prasugrel and active metabolite, has been observed in patients with ACS treated with morphine. This interaction may be related to reduced GI motility and apply to other opioids.

 

Atrial fibrillation and human immunodeficiency virus type‐1 infection: a systematic review: Implications for anticoagulant and antiarrhythmic therapy

British Journal of Clinical Pharmacology

Authors of this narrative review reflect that HIV infection increases the risk of stroke. Choosing antiretrovirals with the lowest drug–drug interaction and with lower impact on the cardiovascular system, and the use of DOACs may help reduce the risk of stroke in this group.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

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

Chest

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.

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

 

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.

 

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

 

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

 

 

 

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.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

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

Circulation

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.

 

 

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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services

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