Friday, 29 May 2020 20:07

Anticoagulation news items. Week commencing 2nd March to 25th May 2020

Impact of direct oral anticoagulant off‐label doses on clinical outcomes of atrial fibrillation patients: A systematic review

British Journal of Clinical Pharmacology
This analysis of 75 observational studies (mainly retrospective) found 25-50% received off-label DOAC doses. Only three directly correlated DOAC dose adjustment with clinical outcome; both under-dosing and over-dosing were associated with an increased risk for adverse events.


Meta-Analysis of Intraocular Bleeding With Dual Antiplatelet Therapy Using P2Y12 Inhibitors Prasugrel or Ticagrelor

American Journal of Cardiology
Review of 4 RCTs (n=42,850) reports no statistically significant increase in the risk of intraocular bleeding with dual antiplatelet therapy using potent P2Y12 inhibitors compared with clopidogrel (40 events v 45 events respectively, risk ratio 0.89, 95% CI 0.58 to 1.36).


Clinical Commissioning Policy: Human coagulation factor X for hereditary factor X deficiency (all ages)

NHS England
NHS England will commission human coagulation factor X in hereditary factor X deficiency (all ages) in accordance with the criteria outlined within the commissioning document.


Effectiveness and Safety of Apixaban Compared With Rivaroxaban for Patients With Atrial Fibrillation in Routine Practice: A Cohort Study

Annals of Internal Medicine
Retrospective analysis of data from 39,351 patients on apixaban, and 39,351 matched patients on rivaroxaban concludes those prescribed apixaban had a lower rate of both ischaemic stroke or systemic embolism and bleeding compared with those prescribed rivaroxaban.


Apixaban versus Warfarin in Patients with Atrial Fibrillation and Advanced Chronic Kidney Disease

Study of 269 patients enrolled in ARISTOTLE found that among patients with AF and CrCl 25-30 mL/min, apixaban caused less major bleeding than warfarin (HR 0.34, 95% CI, 0.14-0.80) and major or clinically relevant non-major bleeding (HR 0.35, 95% CI 0.17-0.72).


Venous thromboembolic diseases: diagnosis, management and thrombophilia testing – guidance (NG158)

National Institute for Health and Care Excellence
This guideline covers diagnosing and managing venous thromboembolic diseases in adults. It aims to support rapid diagnosis and effective treatment for people who develop DVT or PE, and covers testing for conditions that can make a DVT or PE more likely.


Rivaroxaban in Peripheral Artery Disease after Revascularization

New England Journal of Medicine
RCT (n=6,564) found that rivaroxaban plus aspirin was superior to aspirin plus placebo for a composite cardiovascular efficacy outcome (multiple cardiovascular outcomes including cardiovascular death) – 17.3% vs 19.9%, HR 0.85, 95% CI 0.76-0.96).


Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation

New England Journal of Medicine
RCT (n=313) found that in patients undergoing TAVI, composite of death from cardiovascular causes, non–procedure-related bleeding, stroke, or myocardial infarction was lower for anticoagulation (AC) alone vs AC plus clopidogrel (31.2% vs 45.5%, -14.3%, 95% CI -25.0 to -3.6).


Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer

New England Journal of Medicine
RCT (n=1,155) found that apixaban was non-inferior to subcutaneous dalteparin for recurrent VTE (5.6% vs 7.9%, p<0.001 for non-inferiority). Major bleeding rates were similar (3.8% vs 4.0%, HR 0.82, p=0.60 for difference).


Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery

New England Journal of Medicine
RCT (n=3,604) found that rivaroxaban was more effective than enoxaparin in the prevention of venous thromboembolic events during a period of immobilisation after nonmajor orthopaedic surgery of the lower limbs (0.2% vs 1.1%, RR 0.25, 95%CI 0.09-0.75).


The Role of Combination Antiplatelet and Anticoagulation Therapy in Diabetes and Cardiovascular Disease: Insights from the COMPASS Trial

Analysis of the COMPASS trial found that aspirin & rivaroxaban 2.5 mg twice daily provided similar relative benefits on coronary, cerebrovascular, & peripheral endpoints in those with & without diabetes. Absolute benefits in diabetes were higher due to higher baseline risk.


Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome: Role of Lipoprotein(a) and Modification by Alirocumab: Prespecified Analysis of a Randomized Clinical Trial

Pre-specified analysis of the ODYSSEY OUTCOMES RCT (n=18,924) found that the risk of peripheral artery disease (PAD) events is related to lipoprotein(a) level, but not baseline LDL level. Alirocumab reduced PAD events (HR 0.69, 95% CI 0.54-0.89) in this study vs placebo.


The Effect of PCSK9 Inhibition on the Risk of Venous Thromboembolism

Post-hoc analysis of FOURIER and ODYSSEY OUTCOMES trials found evolocumab provided a 31% reduction in VTE vs placebo (p=0.007). The efficacy of evolocumab was higher in patients with a higher baseline Lp(a) level, with authors suggesting Lp(a) modification may attenuate VTE risk.


The Risk / Benefit Tradeoff of Antithrombotic Therapy in Patients with Atrial Fibrillation Early and Late After an Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights from AUGUSTUS

Post-hoc analysis of AUGUSTUS RCT (P2Y12 + aspirin/placebo, and apixaban/vitamin K antagonist, VKA) found that apixaban had a lower or similar risk of bleeding & ischemic outcomes vs VKA and that there was a trade off for aspirin vs placebo for bleeding and ischaemic events.


US FDA Approves Sevenfact [coagulation factor VIIa (recombinant)-jncw] for adults and adolescents with haemophilia A or B and inhibitors

Biospace Inc.
This medicine has been approved for the treatment and control of bleeding episodes occurring in people aged >/=12 years with haemophilia A or B with inhibitors (neutralising antibodies). The active ingredient is expressed in genetically engineered rabbits.


Should You Treat This Acutely Ill Medical Inpatient With Venous Thromboembolism Chemoprophylaxis?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center

Annals of Internal Medicine
A haematologist and a hospital doctor reflect on care of a woman hospitalised for a rheumatologic disorder. They consider risks/benefits of chemoprophylaxis, discuss VTE risk stratification (based on US guidance), and recommend which patients should receive chemoprophylaxis.


Factor Xa Inhibitor-Related Intracranial Hemorrhage (FiX-ICH): Results from a Multicenter, Observational Cohort Receiving Prothrombin Complex Concentrates

This retrospective, observational study found administration of prothrombin complex concentrates after apixaban or rivaroxaban-related intracranial haemorrhage was associated with excellent or good haemostasis in 81.8% (95% CI 77.9-85.2%), with a 3.8% thrombosis rate.


Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19

The Lancet
Analysis of a nationwide dataset from China (n=1099) found that among the patients with COVID-19 at high risk of VTE in this cohort, 44 (11%) of 407 also had a high risk of bleeding, highlighting need to adjust dose and duration of anticoagulants and use of mechanical compression.


Rivaroxaban Plasma Levels and Levetiracetam: A Case Report

Annals of Internal Medicine
Animal studies suggest levetiracetam acts as a P-glycoprotein inducer to reduce rivaroxaban plasma levels. This paper presents first reported case of levetiracetam affecting rivaroxaban plasma levels in a human, leading to clinically important reduction in anticoagulation effect.


Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi

JAMA Cardiology
Study (n=514) found DOAC linked to higher risk of stroke/systemic embolism vs. warfarin (HR 2.71; 95% CI, 1.31-5.57; p= 0.01), challenging assumption of DOAC equivalence with warfarin for LV thrombi and highlights need for RCTs to determine most effective treatment strategies.


Pulmonary Embolism in COVID-19 Patients: Awareness of an Increased Prevalence

In this letter, authors describe a case-series of COVID-19 patients with pulmonary embolism (PE) admitted into ICU over a period of 1 month, at a single institution in France compared to the same period a year ago, noting a doubling in incidence of PE.


Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19

New England Journal of Medicine
In this study of 216 patients with Covid-19 and a prolonged aPTT, 91% were positive for lupus anticoagulant. In the authors opinion however, a prolonged aPTT alone should not be a barrier to the use of anticoagulation in the prevention and treatment of VTE in Covid-19.


Call to Action to Prevent Venous Thromboembolism in Hospitalized Patients: A Policy Statement From the American Heart Association

This policy statement provides a focused review of VTE, risk scoring systems, prophylaxis, and tracking methods. From this summary, 5 major areas of policy guidance are presented that it is hoped will lead to better implementation, tracking, and prevention of VTE events.


Graduated compression stockings as adjuvant to pharmaco-thromboprophylaxis in elective surgical patients (GAPS study): randomised controlled trial

British Medical Journal
RCT (n=1905 in UK) found pharmaco-thromboprophylaxis alone is non-inferior to its use in combination with graduated compression stockings (imaging confirmed lower limb DVT or PE with symptoms within 90 days of surgery occurred in 1.7% on LMWH vs. 1.4% on LMWH and GCS).


Covid-19 and thrombosis: what do we know about the risks and treatment?

British Medical Journal
This BMJ news report discusses the observed increased risk of thrombosis in patients with Covid-19. One expert notes that there are still high rates of DVT, PE and immunothrombosis in Covid-19 patients despite prophylaxis, with some arguing that bigger doses should be given.


Association Between Treatment With Apixaban, Dabigatran, Rivaroxaban, or Warfarin and Risk for Osteoporotic Fractures Among Patients With Atrial Fibrillation: A Population-Based Cohort Study

Annals of Internal Medicine
Study (n=23,515) suggests DOAC use may result in lower risk for osteoporotic fracture vs. warfarin (propensity score–weighted cumulative incidence differences: apixaban, −0.88%, dabigatran, 0.81%, rivaroxaban, −1.13%). Fracture risk does not seem to be altered by choice of DOAC.


Deep Vein Thrombosis in Hospitalized Patients with Coronavirus Disease 2019 (COVID-19) in Wuhan, China: Prevalence, Risk Factors, and Outcome

Study found prevalence of DVT is high and linked to adverse outcomes in hospitalised patients with COVID-19; of 143 patients, 66 (46.1%) developed lower extremity DVT. It suggests VTE prophylaxis may be protective in patients with Padua protection score ≥ 4 after admission.


Coagulation abnormalities and thrombosis in patients with COVID-19

The Lancet Haematology
In this Comment, the authors summarise the characteristics of COVID-19 coagulopathy, coagulation laboratory findings in affected patients, the prohaemostatic state and incidence of thromboembolic events, and potential therapeutic interventions.


Trends in oral anticoagulant prescribing in individuals with type 2 diabetes mellitus: a population-based study in the UK

BMJ Open
Study (n=361 635 with diabetes; 36 570 prescribed oral anticoagulant [OAC]) reported 50% increase in prevalence of OAC prescribing from 2001- 2015. Warfarin prescribing decreased by 14.0% and prescribing of DOACs increased (0.1 to 17.6 per 100 persons on OACs) during this period.


COVID-19-associated hyperviscosity

The Lancet
Letter describes COVID-19-associated hyperviscosity, a potentially severe consequence of infection with severe acute respiratory syndrome coronavirus 2, in 15 patients tested to date. Authors are exploring any beneficial role of therapeutic plasma exchange.


COVID-19 coagulopathy: an evolving story

The Lancet Haematology
Commentary details the increased incidence of thrombotic complications with COVID-19, and how it can resemble other systemic coagulopathies. It concludes that there is still much to be learned, but the fast and ongoing collaboration worldwide makes for a hopeful outcome.


Revised SPC: Clexane (enoxaparin) preparations

electronic Medicines compendium
SPC now states that for IV (bolus) injection (for acute STEMI indication only), in order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 300 IU/ml (3 mg/ml). Instructions for subsequent administration are also given.


Low molecular weight heparins – should treatment doses be used in patients with renal impairment?

Specialist Pharmacy Service
This updated Medicines Q & A reviews and summarise the evidence available for low molecular weight heparin (LMWH) treatment doses in renal impairment. It summarises ESC advice but states that more comparative data (between LMWHs and unfractionated heparin) are required.


Risk of major bleeding among users of direct oral anticoagulants combined with interacting drugs: A population‐based nested case–control study

British Journal of Clinical Pharmacology
This study (393 cases, 1494 controls) found among new DOAC users, concurrent use of antiplatelets (adjusted odds ratio 2.01; 95% CI 1.29–3.11) and SSRIs (1.68; 1.10–2.59) was associated with increased risk of major bleeding. Pharmacokinetic interacting drugs did not increase risk.




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