Items filtered by date: December 2019

Association of bleeding severity with mortality in extended thromboprophylaxis of medically ill patients in the MAGELLAN and MARINER trials

Circulation
Post hoc analysis of rivaroxaban studies found all-cause mortality (ACM) for patients with nonmajor clinically relevant bleeding (BL) vs. no BL not increased in MARINER (HR 0.43;P=0.235) but increased in MAGELLAN (1.74;P=0.021). Major BL was not linked to higher ACM incidence.

 

Small volume intramuscular injections in people taking oral anticoagulants

Specialist Pharmacy Service
This resource covers guidance and evidence, practical advice for healthcare professionals, product prescribing information, advice on vaccines, including influenza and covid-19, and includes section on injecting hydroxocobalamin subcutaneously, and possible alternatives.

 

 

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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Effect of polypharmacy on bleeding with rivaroxaban versus vitamin K antagonist for treatment of venous thromboembolism

Journal of Thrombosis and Haemastasis
Study (n=8246) found reduced bleeding with rivaroxaban (R) vs enoxaparin/VKA in pts without comedication but similar risk in pts with ≥4 comedications. CYP3A4 +/- P-gp inhibitors were associated with doubled bleeding risk vs no use, with no difference between R and enoxaparin/VKA.

 

Thromboembolic Events in JAK inhibitors: A Pharmacovigilance Study From 2012 to 2021 Based on FAERS

British Journal of Clinical Pharmacology
Study covered 8 types of JAKinibs already on the market, and found several safety signals with embolic and thrombotic events linked to use of ruxolitinib, tofacitinib IR and XR, baricitinib, upadacitinib and filgotinib. Some of these signals require further confirmatory data.

 

Does co-prescribing non-steroidal anti-inflammatory drugs and oral anticoagulants increase the risk of major bleeding, stroke and systemic embolism?

British Journal of Clinical Pharmacology
In this cohort study (n=6354) it was shown that concomitant use of NSAIDs with oral anticoagulants (OAC) increased the risk of GI bleeding (HR 3.0, 95%CI: 1.6 to 5.6) and reduced the protective effect against stroke (HR 2.7: 1.5 to 5.1) compared to OAC alone.

 

 

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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Effect of 15-mg Edoxaban on Clinical Outcomes in 3 Age Strata in Older Patients With Atrial Fibrillation: A Prespecified Subanalysis of the ELDERCARE–AF Randomized Clinical Trial

JAMA Cardiology
Subanalysis (n=984) found among Japanese patients age ≥80 years not suitable for standard dose DOACs, 15mg OD dose of edoxaban was superior to placebo in preventing stroke/systemic embolism, albeit with numerically, but non-statistically significantly, higher incidence of bleeding.

 

 

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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Management of combined oral antithrombotic therapy by an Antithrombotic Stewardship Program: a prospective study

British Journal of Clinical Pharmacology
Study (n=460) found implementation of an antithrombotic stewardship program (ASP) improved use and safety of antithrombotic medication (ATM), with 54.6% of patients requiring ≥1 intervention from the ASP to optimise care (most commonly to define maximum duration of combined ATMs).

 

Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study

British Medical Journal
Study (n=1057174 matched to 4076342controls, Sweden) suggests covid-19 is risk factor for DVT,PE & bleeding with incidence rate ratios vs. control period significantly increased 70, 110 & 60 days after covid-19, respectively, particularly with more severe covid-19 & comorbidities.

 

Edoxaban versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism after TAVR: The ADAPT-TAVR Randomized Clinical Trial

Circulation
RCT (n=229) reports after transcatheter AVR, incidence of leaflet thrombosis was numerically but not statistically significantly lower with edoxaban vs dual antiplatelets (9.8% v 18.4%;p=0.076) & no difference in new cerebral thromboembolism & neurological/neurocognitive function.

 

Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study

The Lancet
RCT (n=753) found asundexian 20 and 50mg daily linked to lower observed rates of bleeding vs. apixaban (ratios of incidence proportions = 0.33;90% CI 0.09–0.97 for 20 & 50mg groups[2 events] v apixaban[6 events]), which was achieved despite near complete in-vivo FXIa inhibition.

 

 

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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Disparities in oral anticoagulation initiation in patients with schizophrenia and atrial fibrillation: a nationwide cohort study

British Journal of Clinical Pharmacology
Danish registry study (n= 673 matched 1:5 to incident AF patients without schizophrenia) found that initiation of oral anticoagulation within first year after diagnosis was substantially lower among patients with AF & schizophrenia compared with matched AF peers (33.7% vs. 54.4%).

 

 

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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Association of Type of Oral Anticoagulant Dispensed With Adverse Clinical Outcomes in Patients Extending Anticoagulation Therapy Beyond 90 Days After Hospitalization for Venous Thromboembolism

Journal of the American Medical Association
Cohort study (n=64,642) found a lower incidence of recurrent VTE for apixaban vs warfarin (9.8 vs 13.5/1000 person-years, HR 0.69, 95%CI 0.49-0.99), but no difference for apixaban vs rivaroxaban & rivaroxaban vs warfarin. Rates of major bleeding were similar for all treatments.

 

Physicians Adherence to Evidence-Based Guidelines as a Major Predictor to Anticoagulant-related Medication Errors Incidence and Severity

British Journal of Clinical Pharmacology
Study in tertiary hospital (n=116 with 2166 anticoagulant doses[ADs]) noted 44% prescribed ADs resulted in medication errors (MEs) & major predictor in increasing both MEs incidence & severity is physician adherence to evidence-based guidelines (OR 24.67; 95% CI 5.54–207;p<0.001).

 

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Journal of the American Medical Association
RCT (n=1,557) found antiplatelet therapy (aspirin or P2Y12 inhibitor), vs no antiplatelet therapy, had a low likelihood of improving organ support–free days (composite of in-hospital mortality and duration of ICU–based respiratory or cardiovascular support) within 21 days.

 

How to handle a delayed or missed dose of edoxaban in patients with non-valvular atrial fibrillation? A model-informed remedial strategy

British Journal of Clinical Pharmacology
Simulation study exploring remedial strategies for edoxaban non-adherence recommends the missed dose can be taken immediately if the delay time is ≤11 h. A half dose followed by regular dosing is recommended for 12-19 h delay, and a full followed by half dose for a delay >19 h.

 

 

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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Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial

The Lancet
RCT (n=663), stopped early due to safety concerns, found risk of symptomatic intracranial haemorrhage was higher in patients randomised to aspirin (14% v 7% in those not on aspirin; adjusted OR 1.95 [95% CI 1.13–3.35]) and unfractionated heparin (13% v 7%; 1.98 [1.14–3.46]).

 

Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome: The STOPDAPT-2 ACS Randomized Clinical Trial

JAMA Cardiology
RCT (n=4136) found effectiveness of clopidogrel monotherapy after 1 to 2 months of dual antiplatelet therapy (DAPT) is inconclusive (1-year incidence rate of primary end point of CV & bleeding events = 3.2% vs. 2.8% in 12-month DAPT group, failing to meet noninferiority criteria).

 

Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis of randomised trials

British Medical Journal
Review (68 RCTs; n=45 445) found DOACs & low/high dose LMWH reduced VTE vs.no active treatment (OR 0.17, 95% CI 0.07-0.41; 0.33, 0.16-0.67; 0.19; 0.07-0.54) but probably increase major bleeding (2-3 fold) to similar extent; DOACs probably prevent symptomatic VTE to greater extent.

 

Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study

European Heart Journal
Study (n=59,076) suggests NOACs may be linked to positive net clinical benefit, with lower stroke rate (HR 0.72; 95% CI 0.56–0.94) & no increase intracranial haemorrhage (ICH) risk vs. no treatment & similar stroke rate vs. VKAs but lower rate ICH with NOACs (HR 0.63; 0.42–0.94).

 

DTB Select: Risk of gastrointestinal bleeding with concomitant NOAC and glucocorticoid treatment

Drug and Therapeutics Bulletin
Summary and context are provided on a case-control study that found concomitant treatment with a NOAC and an oral glucocorticoid was associated with a modest increase in the risk of a bleeding event compared with no glucocorticoid exposure.

 

Evaluation of antithrombotic use and COVID-19 outcomes in a nationwide atrial fibrillation cohort

Heart
Study found pre-existing antithrombotic use associated with lower odds of Covid-related death (OR 0.92, 95%CI 0.87-0.96) and although this link may not be causal, researchers suggest it provides further incentive to improve antithrombotic coverage for eligible individuals with AF.

 

 

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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Anticoagulation for the initial treatment of venous thromboembolism in people with cancer

Cochrane Database of Systematic Reviews
Updated review including 15 RCTs (n=1615) found low molecular weight heparin is probably superior to unfractionated heparin for initial VTE treatment in cancer. Additional trials focusing on patient‐important outcomes will further inform the questions addressed in this review.

 

Prevalence and management of drug interactions between NSAID and antithrombotics in ambulatory care

British Journal of Clinical Pharmacology
This article discusses a prospective intervention study of 782 interactions from an older, polymedicated patient population. It found anticoagulants were involved in 16.1% of the cases and for 61% of all cases, the interacting drugs were prescribed by the same physician.

 

Two-year outcomes of UK patients newly diagnosed with atrial fibrillation: findings from the prospective observational cohort study GARFIELD-AF

British Journal of General Practice
Anticoagulation (AC) treatment vs no AC was linked to significantly lower all-cause mortality & risk of non-haemorrhagic stroke/ systemic embolism (aHR 0.70; 95% CI 0.53 to 0.93 & 0.39; 95% CI 0.24-0.62) and a non-significant higher risk of major bleeding (1.31;95% CI 0.77-2.24).

 

Comparative efficacy and safety of oral anticoagulants for the treatment of venous thromboembolism in the patients with different renal functions: a systematic review, pairwise and network meta-analysis

BMJ Open
Review (10 RCTs; n=37,298) found no significant differences in efficacy of DOACs among the three creatinine clearance subgroups, for acute or extended treatment of VTE. Aapixaban may be associated with lower bleeding risk in CrCl >80 mL/min subgroup; confirmation is needed.

 

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism

Cochrane Database of Systematic Reviews
Review (34 studies; n=14,931) found combining intermittent pneumatic leg compression (IPC) with pharmacological prophylaxis (PP) reduces incidence of PE & DVT vs. IPC alone (low‐certainty evidence [LCE]). Compared to PP alone, it also reduces incidence of PE(LCE) & DVT (high‐CE).

 

Oral antiplatelet therapy for acute ischaemic stroke

Cochrane Database of Systematic Reviews
Updated review (11 studies, n=42,226) found antiplatelet therapy with aspirin 160-300 mg daily started within 48 hours significantly decreased death & dependency, and reduced risk of early recurrent stroke without a major risk of early haemorrhagic complications.

 

Heparin versus citrate anticoagulation for continuous renal replacement therapy in intensive care: the RRAM observational study

National Institute for Health Research
Analysis of responses to survey from 181 NHS adult general ICUs in England, Wales (n=69,001) found change to regional citrate anticoagulation was not linked to step change in 90-day mortality (OR 0.98, 95% CI 0.89 to 1.08) and is likely to have substantially increased costs.

 

 

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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Triple antithrombotic therapy and dual therapy – What is the evidence base?

British Journal of Clinical Pharmacology
Triple antithrombotic therapy refers to concurrent use of oral anticoagulant in combination with dual antiplatelet therapy. Review makes recommendations on duration, noting recommendations in guidelines will remain in flux until there is conclusive evidence about when to step down.

 

Association between oral anticoagulants and COVID-19 related outcomes: a population-based cohort study

British Journal of General Practice
Among 52,832 current oral anticoagulant (OAC) users and 18,271 non-users with low baseline stroke risk (CHA₂DS₂-VASc score 2), those on OACs had a lower risk of testing positive for SARS-CoV-2 (aHR, 0.77, 95%CI, 0.63–0.95) and severe COVID-19 outcomes than non-users.

 

Intravenous thrombolytic treatment and endovascular thrombectomy for ischaemic wake‐up stroke

Cochrane Database of Systematic Reviews
Review of 7 trials (n=980) found both IV thrombolysis and endovascular thrombectomy of large vessel occlusion improved functional outcome without increasing risk of death, but, a possible increased risk of symptomatic intracranial haemorrhage with thrombolysis cannot be ruled out.

 

Treatment Strategies for Proximal Deep Vein Thrombosis: A Network Meta-analysis of Randomised Controlled Trials

European Journal of Vascular and Endovascular Surgery
Review (7 RCTs) found ultrasound assisted catheter directed thrombolysis may improve patency rates vs the other treatment modalities. However, no treatment modality showed superiority in reduction of post-thrombotic syndrome and overall quality of available evidence was poor.

 

 

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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Impact of P-glycoprotein and/or CYP3A4-interacting drugs on effectiveness and safety of NOACs in patients with atrial fibrillation: a meta-analysis

British Journal of Clinical Pharmacology
Review (15 studies) found in AF patients treated with NOACs, concomitant use of P-gp/CYP3A4 inhibitors was associated with higher risk of major bleeding (RR 1.10, 95% CI 1.01-1.19) and all-cause mortality (1.14, 95% CI 1.05-1.23); authors recommend close monitoring.

 

Risk factors associated with venous and arterial neonatal thrombosis in the intensive care unit: a multicentre case-control study

The Lancet Haematology
Study of 118,952 admissions to 31 neonatal intensive care units found bloodstream infection (OR 2.07), maternal diabetes (1.62), abdominal surgery (1.36) and thrombocytopenia (2.44) were the most significant risk factors for venous thrombosis (p<0.0001 for all).

 

Revised SPC: Clexane (enoxaparin)- all presentations

electronic Medicines compendium
SPC updated to warn acute generalised exanthematous pustulosis reported (unknown frequency); patients should be advised of signs/symptoms & monitored for skin reactions, enoxaparin should be withdrawn immediately & alternative treatment considered (as appropriate), if this occurs.

 

Association of Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase

Journal of the American Medical Association
Retrospective study (n=163,038) found NOAC use within past 7 days was not associated with increased risk of intracranial haemorrhage among patients with acute ischaemic stroke treated with alteplase (3.7% vs 3.2% in those not taking NOACs; adjusted OR 0.88 [95% CI 0.70 to 1.10]).

 

Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial

Journal of the American Medical Association
Phase 2b trial (n=121) found use of intra-arterial alteplase following thrombectomy resulted in a greater likelihood of excellent neurological outcome (modified Rankin Scale score of 0 or 1) than placebo at 90 days (59.0% vs 40.4%; P=0.047); these findings require confirmation.

 

US FDA grants Fast Track Designation for asundexian for the secondary prevention in patients with non-cardioembolic ischaemic stroke

Biospace Inc.
Asundexian is an oral inhibitor of Factor Eleven (FXIa) that is also being developed for atrial fibrillation and recent myocardial infarction. It is currently in Phase II clinical trials in all three conditions either as monotherapy or in combination with antiplatelets.

 

 

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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