Venous Thromboembolism Prophylaxis in COVID-19: Making Sense of the Evidence

Annals of Internal Medicine
US article discusses evidence regarding VTE prevention in patients hospitalised with Covid-19, the potential reasons behind the differing outcomes between moderately ill and critically ill patients, and makes suggestions on choice of VTE prophylaxis strategy in these patients.

Rivaroxaban 2.5 mg Twice Daily Plus Aspirin Reduces Venous Thromboembolism in Patients With Chronic Atherosclerosis

Circulation
Secondary analysis of the COMPASS trial (27,395) and data review from the VOYAGER PAD study found the vascular benefits of adding rivaroxaban 2.5mg twice daily to aspirin were consistent across age, cancer status number of vascular beds involved and renal function.

Time Course for Benefit and Risk With Ticagrelor and Aspirin in Individuals With Acute Ischemic Stroke or Transient Ischemic Attack Who Carry CYP2C19 Loss-of-Function Alleles: A Secondary Analysis of the CHANCE-2 Randomized Clinical Trial

JAMA Neurology
Analysis of 6,412 patients who carry the CYP2C19 loss of function alleles in RCT comparing ticagrelor to clopidogrel (both with aspirin) found a reduction of major ischaemic events with ticagrelor in the first week, which was attenuated in weeks 2 and 3.

Subclinical Leaflet Thrombosis and Anticoagulation After Transcatheter Aortic Valve Replacement: A Review

JAMA Cardiology
This narrative review discusses several studies that have investigated the role for oral anticoagulation in patients after transcatheter aortic valve replacement, with a focus on the issue of subclinical leaflet thrombosis.

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

Rivaroxaban Monotherapy vs Combination Therapy With Antiplatelets on Total Thrombotic and Bleeding Events in Atrial Fibrillation With Stable Coronary Artery Disease: A Post Hoc Secondary Analysis of the AFIRE Trial

JAMA Cardiology
Analysis (n=2215) found rivaroxaban monotherapy linked to 38% lower risk of total CV & bleeding events, than combination anticoagulant & antiplatelet therapy (HR 0.62; 95% CI, 0.48-0.80; p < 0.001) and mortality risk after a bleeding event was higher than after a thrombotic event.

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

Efficacy and Safety Considerations With Dose-Reduced Direct Oral Anticoagulants: A Review

JAMA Cardiology
Review of 72 RCTs found efficacy & safety results for dose-adjusted DOACs in large RCTs of AF were similar to those for full-dose DOACs. No studies investigating dose adjusted DOACs in acute VTE, but authors suggest low-intensity DOACs are appropriate for approved indications.

Antithrombotic Therapy for Venous Thromboembolism (second update of the chest guideline and expert panel report)

Journal of the American Medical Association
This US guidance recommends outpatient treatment for patients with low-risk pulmonary embolism, DOAC treatment for patients in the acute VTE 3 month treatment phase & oral factor Xa inhibitors for acute VTE treatment in cancer patients in initial and extended treatment phases.

Incidence of nonvalvular atrial fibrillation and oral anticoagulant prescribing in England, 2009 to 2019: A cohort study

PLOS Medicine
Study (between 2009 & 2019; n=12,517,191) using UK CPRD database noted incidence of non valvular AF increased between 2009 and 2015, before plateauing, and underprescribing of oral anticoagulants was liked to a range of comorbidities, ethnicity, and socioeconomic factors.

Factors associated with non-adherence to the use of coumarin derivatives or direct oral anticoagulants: a systematic review of observational studies

British Journal of Clinical Pharmacology
Review (9 studies) found factors linked to non-adherence were heterogeneous; few showed consistent results. Variables reported as risk factors were male sex, hospitalization, Charlson score & bleeding. White race, CHA2DS2VASc (2-9) & polypharmacy reported as protective factors.

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

Risk of intracranial hemorrhage between different direct oral anticoagulants in older patients seen in the emergency department with a head injury: A population-based cohort study

Thrombosis Research
Canadian retrospective study (n=9230; 5.9% with intracranial haemorrhage) found no differences in the risk of intracranial haemorrhage between DOACs (dabigatran vs rivaroxaban; dabigatran vs apixaban; rivaroxaban vs apixaban) and matched cohorts.

A multinational European network to implement integrated care in elderly multimorbid atrial fibrillation patients: the AFFIRMO Consortium

European Heart Journal
This consortium will provide new evidence on specific care models, including risk stratification tools for patients with polypharmacy, which will help to improve clinical management and reduce the risks of major clinical adverse outcomes.

Risk of venous thromboembolism in men with prostate cancer compared with men in the general population: a nationwide population-based cohort study in Sweden

BMJ Open
Swedish study (n=92,105 with prostate cancer, n=466,241 without prostate cancer) found men with prostate cancer had a mean 50% increased risk of VTE during the 5 years following cancer diagnosis vs men without prostate cancer. DVT accounted for 52% of VTE cases in both cohorts.

COMPASS open label extension study results support the long-term use of rivaroxaban (Xarelto®) plus aspirin for vascular protection in patients with chronic Coronary Artery Disease (CAD) and/or Peripheral Artery Disease (PAD)

Biospace Inc.
COMPASS LTOLE study (n=12,964) found rivaroxaban 2.5 mg twice daily + aspirin 75-100 mg daily for up to 3 years was linked to similar/lower incidence rates for major CV events (2.35 vs 2.18/100 patient yrs) & bleeding (1.01 vs 1.67/100 patient yrs) vs randomised treatment phase.

Apixaban or Warfarin and Aspirin or Placebo After Acute Coronary Syndrome or Percutaneous Coronary Intervention in Patients With Atrial Fibrillation and Prior Stroke - A Post Hoc Analysis From the AUGUSTUS Trial

JAMA Cardiology
In this analysis of the subgroup of patients with a history of atrial fibrillation or stroke apixaban was associated with a lower risk of bleeding, death, or hospitalization than warfarin. Patients treated with aspirin had a higher bleeding risk than those receiving placebo.

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

Venous or arterial thrombosis and deaths among COVID-19 cases: a European network cohort study

The Lancet Infectious Diseases
Study (n=909 473; 32 329 hospitalised) found occurrence of venous thromboembolism in patients with COVID-19 was associated with increased mortality (adjusted HRs 4.42 for not hospitalised and 1.63 for hospitalised), as was occurrence of arterial thromboembolism (3.16 and 1.93).

Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial

European Heart Journal
RCT (n=1500) found that after transcatheter aortic valve implantation, apixaban was not superior to standard of care (a vitamin K antagonist or antiplatelet), irrespective of an indication for oral anticoagulation (primary efficacy endpoint HR 0.92; 95% CI 0.73–1.16).

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 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

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

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

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

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