Warfarin and food, herbal or dietary supplement interactions: A systematic review

British Journal of Clinical Pharmacology
Review concluded that healthcare staff should be aware of increased risk of bleeding when following are taken with warfarin: Chinese wolfberry, chamomile tea, cannabis, cranberry, chitosan, green tea, Ginkgo biloba , ginger, spinach, St. John's Wort, sushi and smoking tobacco.

 

Association Between Treatment With Apixaban, Dabigatran, Rivaroxaban, or Warfarin and Risk for Osteoporotic Fractures Among Patients With Atrial Fibrillation

Annals of Internal Medicine
Population-based cohort study (n=23,515, Hong Kong) reports among AF patients, DOAC use may result in lower risk for osteoporotic fracture vs. warfarin at 24-month follow-up, and risk does not seem to be altered by choice of DOAC. Findings may be limited by residual confounding.

 

Revised SPC: Octaplex 1000 IU powder and solvent for solution for injection

electronic Medicines compendium
SPC updated with information on traceability and sodium content, and to note that no data are available regarding its use in the paediatric population. Sections 6.5 and 6.6 contain information on a new Nextaro® device.

 

Revised SPC: Sustanon (testosterone) 250, 250mg/ml solution for injection

electronic Medicines compendium

SPC now notes testosterone should be used with caution in patients with thrombophilia or risk factors for venous thromboembolism, as there have been studies/reports of thrombotic events even under anticoagulation treatment. 'Weight increased' has been added as an adverse effect.

 

Ticagrelor granted FDA Priority Review for secondary prevention of acute ischaemic stroke or transient ischaemic attack

Biospace Inc.
The accepted supplemental new drug application is based on results from the Phase III THALES trial, in which the combination of ticagrelor and aspirin was associated with a reduction in the primary composite endpoint of stroke and death compared to aspirin 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

Safety and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy

European Journal of Hospital Pharmacy

Retrospective study (n=145) reported that INR target was reached in 102 patients, aPTT ratio target was reached in 113 patients, and 79 of 106 patients reversed for bleeding achieved haemostatic effectiveness after four-factor prothrombin complex concentrate (all p<0.0001).

 

Patterns of oral anticoagulation use with cardioversion in clinical practice

Heart
Analysis of AF registry data (n=13 004; 1613 met criteria) reported no differences in death (HR 1.19, 95% CI 0.62 -2.28, p=0.61), stroke/TIA (1.18; 0.30 -4.74; p=0.81) or major bleeding (1.29; 0.66 -2.52; p=0.45) at 1 year in patients treated with DOAC vs vitamin K antagonist.

 

Revised SPC: Tygacil (tigecycline) 50mg powder for solution for infusion

electronic Medicines compendium
Recommendation has been added regarding the need for monitoring of coagulation parameters, including blood fibrinogen, prior to and during tigecycline treatment; as well as a related update to frequency of existing side effect hypofibrinogenaemia from not known to rare.

 

Direct-acting oral anticoagulants (DOACs): reminder of bleeding risk, including availability of reversal agents

Medicines and Healthcare products Regulatory Agency
Alert advises on need to remain vigilant, especially in patients with increased bleeding risks; and that specific reversal agents are available for dabigatran (Praxbind, [idarucizumab]), apixaban and rivaroxaban (Ondexxya [andexanet alfa]).

 

Cangrelor, Tirofiban and Chewed or Standard Prasugrel Regimens in Patients with ST-Segment Elevation Myocardial Infarction: Primary Results of the FABOLUS FASTER Trial

Circulation
RCT (n=122) reports cangrelor provided inferior inhibition of platelet aggregation (IPA) vs. tirofiban; both treatments yielded greater IPA vs. chewed prasugrel (which led to higher active metabolite concentration but not greater IPA compared with standard prasugrel tablet).

 

New product Inhixa (enoxaparin sodium) 30,000 IU (300 mg)/3 mL solution for injection in multidose vial

electronic Medicines compendium
This is new presentation, licensed for VTE treatment and medical and surgical prophylaxis, ACS, treatment of unstable angina & non ST-segment elevation myocardial infarction (NSTEMI), STEMI, and prevention of thrombus formation in extra corporeal circulation during haemodialysis.

 

Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study

The Lancet Haematology
Study (n=68) found coagulation activation is common in hospitalised patients with COVID-19, with elevated plasma von Willebrand factor levels increasing with disease severity. Findings identify a potential prognostic role for measurement of endothelial markers in this setting.

 

Revised SPCs: Pradaxa (dabigatran) hard capsules

electronic Medicines compendium
SPC updated to add 'neutropenia' and 'agranulocytosis' as adverse reactions (frequency not known).

 

 

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

 

Avatrombopag for treating thrombocytopenia in people with chronic liver disease needing a planned invasive procedure – guidance (TA626)

National Institute for Health and Care Excellence
Avatrombopag is recommended as an option for treating severe thrombocytopenia (platelet count of <50,000/microlitre of blood) in adults with chronic liver disease having a planned invasive procedure.

 

Community pharmacy-based study of adherence to non-vitamin K antagonist oral anticoagulants

Heart
Belgian study (n=766) found a positive patient attitude towards DOAC therapy, with 21% reporting non-adherence according to the Medication Adherence Report Scale, and unintentional non-adherence being the most commonly reported reason (15.4%).

 

 

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

Piperacillin/tazobactam-induced coagulopathy in a patient through a vitamin K-dependent mechanism

European Journal of Hospital Pharmacy

Case report describes 70-year-old female patient whose INR increased following piperacillin/tazobactam (PTZ). Coagulopathy was reversed with vitamin K, suggesting PTZ can induce coagulopathy through a vitamin K-dependent mechanism.

 

DTB Select: DOAC dose adjustment in renal impairment

Drug and Therapeutics Bulletin
Commentary and context are provided for a US registry-based study (n=6,682) which found that of the 4% of people treated with a DOAC who met the criteria for a dose reduction, only 20% of them had an appropriate dose adjustment.

 

Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial

Journal of the American Medical Association
RCT (n=3056) found composite endpoint of major bleeding and CV and cerebrovascular events was less frequent with ticagrelor monotherapy vs dual therapy with aspirin (3.9% vs 5.9%, HR 0.66, p=0.01) but lower than expected event rates should be considered when interpreting results.

 

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

The Lancet
This RCT in adults with severe GI bleeding (n=12,009) found no difference between tranexamic acid and placebo in death due to bleeding within 5 days (4% v 4%; RR 0.99; 95% CI 0.82-1.18) with a higher risk of VTE events (1.85; 95% CI 1.15-2.98) and seizures (1.73; 1.03-2.93).

 

The Safety and Efficacy of Aspirin Discontinuation on a Background of a P2Y12 Inhibitor in Patients after Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Circulation
Meta-analysis of 5 RCTs (n=32,145) found discontinuation of aspirin therapy 1-3 months post PCI reduced major bleeding risk vs continued dual antiplatelet therapy (1.97% vs 3.13%; HR 0.60, 95% CI 0.45-0.79), with no observed increase in MACE (2.73% vs 3.11%; HR 0.88, 0.77-1.02).

 

 

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 Hospitalization With Hemorrhage Among Older Adults Taking Clarithromycin vs Azithromycin and Direct Oral Anticoagulants

JAMA Internal Medicine

Study (n=24,943) found concurrent use of clarithromycin compared with azithromycin was associated with a small, significantly greater 30-day risk of hospital admission with major haemorrhage (adjusted hazard ratio, 1.71 [95% CI, 1.20-2.45]; absolute risk difference, 0.34%).

 

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

 

Comparative Efficacy and Safety of Oral P2Y12 Inhibitors in Acute Coronary Syndrome: Network Meta-Analysis of 52,816 Patients from 12 Randomized Trials

Circulation

Ticagrelor reduced CV and all-cause mortality (HR 0.82 and 0.83, respectively) whereas there was no significant mortality reduction with prasugrel vs clopidogrel (0.90 and 0.92, respectively). Both prasugrel and ticagrelor increased major bleeding vs clopidogrel (1.26 and 1.27).

 

One‐year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry

British Journal of Clinical Pharmacology
Prospective study (n=1717) found clopidogrel-treated patients had a higher annual rate of cardiovascular mortality, major adverse cardiovascular event and all‐cause mortality (all P< 0.001) without differences in major bleeding (P = 0.587) vs novel oral P2Y12 inhibitors.

 

 

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

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

Circulation
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

Circulation
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

Circulation
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

Circulation
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

Circulation
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

Circulation
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

Circulation
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

Circulation
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

Circulation
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.

 

 

 

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

 

 

 

 

 

 

Equivalent inpatient mortality among direct-acting oral anticoagulant and warfarin users presenting with major hemorrhage

Thrombosis Research
Database review (1.5 million hospitalisations, and 3731 major haemorrhages) found, after accounting for differences in patient characteristics, location of bleed, and traumatic injury, inpatient survival was no different in patients with major haemorrhage on DOAC or warfarin.

 

Management of acute ischemic stroke

British Medical Journal
This expert review discusses recent updates in secondary prevention recommendations including short term use of dual antiplatelet therapy to prevent recurrent stroke in the high risk period immediately after stroke; as well as emerging therapies and future research.

 

Oral Anticoagulation for Patients With Atrial Fibrillation on Long-Term Hemodialysis

Journal of the American College of Cardiology

Review of 16studies (n=71,877) concludes oral anticoagulants (OAC) are not associated with reduced risk of thromboembolism in patients with AF on long-term dialysis; warfarin, dabigatran, and rivaroxaban were associated with significantly higher bleeding risk v apixaban or no OAC.

 

P2Y12 inhibitors with oral anticoagulation for percutaneous coronary intervention with atrial fibrillation: a systematic review and meta-analysis

Heart
Review of 7 studies (n=22,014) concludes when compared with clopidogrel, use of ticagrelor (RR 1.36; 95% CI 1.18 to 1.57) and prasugrel (RR 2.11; 95% CI 1.34 to 3.30) were associated with increased rates of bleeding in patients with AF on oral anticoagulants undergoing PCI.

 

Gastrointestinal bleeding and the risk of colorectal cancer in anticoagulated patients with atrial fibrillation

European Heart Journal
Retrospective study suggests lower GI-bleeding during oral anticoagulant therapy should not be dismissed as benign consequence of treatment but always examined for potential underlying malignant cause (absolute 1yr risk:3.7 to 8.1% in age groups ≤65 and 76–80 yrs, respectively).

 

Atrial fibrillation patients’ experiences and perspectives of anticoagulation therapy changes

Research in Social and Administrative Pharmacy
A thematic analysis on qualitative data from 56 AF patients who experienced a therapy change identified clear opportunities to improve patients' experiences with oral anticoagulant therapy changes through improved shared decision-making and patient education/counselling.

 

Clinical Effectiveness and Safety of Aspirin for Venous Thromboembolism Prophylaxis After Total Hip and Knee Replacement A Systematic Review and Meta-analysis of Randomized Clinical Trials

JAMA Internal Medicine
Review of 13 RCTs (n=6060) concludes risk of VTE and adverse effects (risk of major bleeding, wound haematoma or infection) after total hip and knee replacement was not statistically significantly different when using aspirin vs other anticoagulants.

 

Fracture risks among patients with atrial fibrillation receiving different oral anticoagulants: a real-world nationwide cohort study

European Heart Journal
Taiwanese study (n=19,414) concludes that compared with warfarin, non-vitamin K antagonist oral anticoagulants were associated with a reduced fracture risk (Hazard Ratio = 0.84, 95% CI 0.77–0.93; P<0.001).

 

Lower versus Standard INR Targets in Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Thrombosis and Haemostasis
Review of 74 RCTs (n=11,322) found that compared with standard INR target (2-3), lower INR ranges (1.5-2) were associated with higher rates of thromboembolism (7.1% vs 4.4%), lower rates of major bleeding (2.2.vs. 4.4%), and similar mortality rates (4.8 v 5.2%).

 

Optimal Antithrombotic Regimens for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: An Updated Network Meta-analysis

JAMA Cardiology
Analysis of 5 RCTs (n = 11 542) suggests vitamin K antagonist plus dual antiplatelet therapy should generally be avoided in this population as regimens in which aspirin is discontinued may lead to lower bleeding risk and no difference in antithrombotic effectiveness.

 

Risk of pregnancy-related venous thromboembolism and obstetrical complications in women with inherited type I antithrombin deficiency: a retrospective, single-centre, cohort study

The Lancet Haematology
Study(n=87) confirms this population have high risk of 1st/recurrent VTE during pregnancy,with highest risk in women with +ve family history(FH), but still relevant in those with–ve FH suggesting low-molecular-weight heparin prophylaxis should also be considered in these patients.

 

 

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 SPC: Pradaxa (dabigatran) capsules

electronic Medicines compendium

SPC now advises that concomitant administration with glecaprevir/pibrentasvir is contraindicated owing to increased risk of bleeding due to increased dabigatran levels. Also, alopecia has been added as a potential adverse effect of treatment (frequency unknown).

 

Meta-Analysis Comparing Double Versus Triple Antithrombotic Therapy in Patients With Atrial Fibrillation and Coronary Artery Disease

American Journal of Cardiology

Review of 9 studies (n=13,437) found no statistically significant difference in mortality, nonfatal myocardial infarction, stent thrombosis, and stroke between double and triple antithrombotic therapy (DATT and TATT). DATT had a lower rate of bleeding (RR 0.64, 95% CI 0.54-0.75).

 

Association of Ticagrelor vs Clopidogrel With Major Adverse Coronary Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

JAMA Internal Medicine

Cohort study (n=11,185) concludes ticagrelor was not associated with lower risk of major adverse coronary events (HR 0.97; 95% CI, 0.85-1.10); however, it was associated with an increased risk of major bleeding (1.51; 1.29-1.78) and dyspnoea vs clopidogrel (1.98; 1.47-2.65).

 

Effect of Osocimab in Preventing Venous Thromboembolism Among Patients Undergoing Knee Arthroplasty The FOXTROT Randomized Clinical Trial

Journal of the American Medical Association

RCT (n=813) reports postoperative osocimab 0.6mg/kg, 1.2mg/kg, and 1.8mg/kg met criteria for noninferiority vs enoxaparin, and the preoperative 1.8mg/kg dose of osocimab met criteria for superiority vs enoxaparin in incidence of VTE (primary outcome) at 10-13 days postoperatively.

 

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

Specialist Pharmacy Service

In contrast to unfractionated heparin, low molecular weight heparins are primarily cleared via kidney thus care needed in renal impairment (RI) because they can accumulate and increase bleeding Risk. Q&A reviews current literature on use of prophylactic doses in patients with RI.

 

Direct acting oral anticoagulants and alopecia: the valuable support of post marketing data

British Journal of Clinical Pharmacology

Analysis identified 1316 reports on VigiBase, most concerning rivaroxaban (58.8%). Overall, 80% of reports were related to females, in particular to those ≥65 years old (23.1%).Median time‐to‐onset was 28 days (IQR 63 days). In 54.3% of reports, causality was assessed as possible.

 

Efficacy and Safety of Nonvitamin K Oral Anticoagulants in Patients with Atrial Fibrillation and Cancer: A Study-Level Meta-Analysis

Thrombosis and Haemostasis

In analysis of 3 RCTs (n=2661), use of NOACs was linked to similar incidence of stroke/systemic embolism, ischaemic stroke, venous thromboembolism, all-cause death and major bleeding vs. vitamin K antagonists. Results were confirmed in secondary analysis (3 observational studies).

 

Ticagrelor hits primary endpoint in the THALES Phase III trial for use in stroke

PharmaTimes
In this study, the manufacturers report that ticagrelor 90 mg twice daily plus aspirin for 30 days showed a statistically significant and clinically meaningful reduction in the risk of stroke and death vs aspirin alone.

 

Committee for Medicinal Products for Human Use (CHMP) issues positive recommendation for new medicine treprostinil sodium (Trepulmix) for treatment of chronic thromboembolic pulmonary hypertension

European Medicines Agency
Treprostinil sodium is a prostacyclin analogue which has a direct vasodilatory effect on pulmonary and systemic arterial circulation, and inhibits platelet aggregation.

 

 

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

 

Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial

Circulation

Review of patients with incident NSAID use in the ARISTOTLE trial (n=2185) found that incident NSAID use was associated with an increased risk of major bleeding (HR 1.61, 95% CI 1.11-2.33) and relevant non-major bleeding (1.70, 1.16-2.48).

 

Decline in renal function and oral anticoagulation dose reduction among patients with atrial fibrillation

Heart

US-Registry shows among 4120 patients on DOACs, 154 (3.7%) patients had a CrCl decline sufficient to warrant FDA-recommended dose reductions and only 31 patients underwent dose reduction. Those without dose reduction experienced major bleeding 1.7% vs 0% at 1 year.

 

Apixaban and dalteparin in active malignancy‐associated venous thromboembolism: The ADAM VTE trial

Journal of Thrombosis and Haemastasis

RCT (n=300) found a lower rate of major bleeding and recurrent VTE with apixaban vs dalteparin (0% vs 1.4% and 0.7% vs 6.3%, p<0.05 for both). Rates of major bleeding or clinically relevant non-major bleeding were similar in the two groups (6%).

 

 

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

Page 1 of 30