Safety and efficacy of different prophylactic anticoagulation dosing regimens in critically and non-critically ill patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials

European Heart Journal-Cardiovascular Pharmacotherapy
Review (7 RCTs; n=5,154) found escalated-dose prophylactic anticoagulation was associated with lower rates of VTE (2.5% vs. 4.7%; RR 0.55, 95% CI 0.41–0.74) but no benefit on other outcomes vs standard dose; and it increased risk of major bleeding (2.4% vs. 1.4%).

 

Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR

European Heart Journal
This pre-specified analysis of the TWILIGHT trial found withdrawal of aspirin after 3 months in those with no events reduced bleeding risk (6.3% vs. 11.4%; HR 0.53, 95% CI 0.35–0.82) without increasing ischaemic events when compared to continued aspirin and ticagrelor.

 

Antithrombotic Therapy in Patients Undergoing Transcatheter Interventions for Structural Heart Disease

Circulation
Review discusses current evidence on the use of antithrombotic therapy in these patients, noting the optimal regimens to adopt in each specific procedure is still unclear, and emphasizing the importance of a tailored approach.

 

Apixaban versus no anticoagulation after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation in the Netherlands (APACHE-AF): a randomised, open-label, phase 2 trial

The Lancet Neurology
RCT (n=101) found over median follow-up of 1.9 years, there was high subsequent annual risk of non-fatal stroke/vascular death, whether allocated to apixaban or to avoid anticoagulation (annual event rate 12·6% vs 11·9%, respectively, HR 1.05; 95% CI 0.48–2.31; p=0.90).

 

 

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 Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants: A Nationwide Propensity Score–Weighted Study

Annals of Internal Medicine
Study (n=2,157) found rates of GI bleeding were higher for rivaroxaban than apixaban (3.2 vs. 2.5 overall events per 100 person-years [HR 1.42; 95% CI 1.04 to 1.93; major bleeding HR 1.50 [1.00 to 2.24]) and dabigatran (similar estimates but including possibility of null effect).

 

All Wales Medicines Strategy Groups consults on draft guidance on oral anticoagulation for non-valvular atrial fibrillation

All Wales Medicines Strategy Group
This consultation presents a proposed update to the current guidance, following the publication of updated NICE guidance (NG196; published June 2021). The update includes re-positioning DOACs before vitamin K antagonists, and an amendment to the tool for assessing bleeding risk.

 

Would You Recommend Aspirin to This Patient for Primary Prevention of Atherosclerotic Cardiovascular Disease?

Annals of Internal Medicine
In this article, two clinicians discuss and debate current guidelines on use of aspirin for primary prevention of atherosclerotic vascular disease, the appropriate risk threshold for starting aspirin therapy, and the role of the coronary artery calcium score in decision making.

 

Reduction in Acute Limb Ischemia with Rivaroxaban versus Placebo in Peripheral Artery Disease after Lower Extremity Revascularization: Insights from VOYAGER PAD

Circulation
Review of VOYAGER PAD study (n=6564) found, in those with prior lower extremity revascularisation, rivaroxaban reduced acute limb ischaemia vs placebo (by 2.6% at 3 years; HR 0.67, 95%CI 0.55 to 0.82) with a benefit starting early (HR 0.45, 0.24 to 0.85 at 30 days after surgery).

 

Anticoagulant prescribing for atrial fibrillation and risk of incident dementia

Heart
In study of healthcare records from UK CPRD (n=39,200 of whom 1258 had dementia [DM]), use of DOAC for AF was linked to 16% reduction in DM diagnosis vs. Vit K antagonist (HR 0.84, 95% CI: 0.73-0.98) & 26% reduction in incident mild cognitive impairment (0.74, 95% CI: 0.65-0.84).

 

Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial

British Medical Journal
This RCT in hospitalised adults with Covid-19 and increased D-dimer levels (n=465; mean BMI 30.3 kg/m2) found therapeutic dose heparin did not reduce the risk of the primary composite endpoint (16.2% v 21.9% prophylactic dose; OR 0.69, 95% CI 0.43 to 1.10; P=0.12).

 

 

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

Temporal Association Between Episodes of Atrial Fibrillation and Risk of Ischemic Stroke

JAMA Cardiology
Cohort study (n=891) found excess stroke risk was highest within 5 days of an episode of atrial fibrillation (AF) of >5.5 hours in duration and diminished rapidly thereafter, thus supporting trials of time-delimited anticoagulation for infrequent multi-hour episodes of AF.

 

Revised SPC: Clexane (enoxaparin) pre-filled syringes

electronic Medicines compendium
SPC updated to note licence extension for use as extended treatment of deep vein thrombosis and pulmonary embolism and prevention of its recurrence in patients with active cancer.

 

Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial

JAMA Internal Medicine
In RCT (n=253), therapeutic-dose LMWH reduced major thromboembolism & death vs institutional standard heparin thromboprophylaxis (28.7 vs 41.9%;RR 0.68; 95% CI, 0.49-0.96;p= 0.03) among inpatients with very elevated D-dimer levels, with no significant difference in major bleeding.

 

Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial

The Lancet
RCT (n= 2697, South Korea) found unguided de-escalation antiplatelet strategy (switching from ticagrelor+aspirin [TA] to clopidogrel+aspirin) was superior to remaining on TA at preventing net adverse clinical events up to 12 months, mainly by reducing bleeding events.

 

 

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

Thromboprophylaxis for children post‐Fontan procedure: Insights From the UNIVERSE Study

Journal of the American Medical Association
RCT (n=112) found that compared to aspirin, rivaroxaban liquid based on body weight–adjusted dosing had similar safety profile (clinically relevant non-major bleeding in 6% vs 9% on aspirin) & fewer thrombotic events (2% vs 9%, respectively), albeit not statistically significant.

 

Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine–Induced Immune Thrombotic Thrombocytopenia

JAMA Neurology
Study of 116 cases of cerebral venous sinus thrombosis (CVST) after covid vaccine found 67.2% had thrombosis with thrombocytopenia syndrome (TTS). In hospital mortality rate was 47% with TTS, 5% without TTS and 3.9% in a control group of patients with CVST before the pandemic.

 

Revised SPC: Clexane (enoxaparin) Forte Syringes

electronic Medicines compendium
SPC has been revised to reflect licence extension covering extended treatment of DVT & PE & prevention of its recurrence in patients with active cancer. Recommended dose is 100 IU/kg (1 mg/kg) BD by SC injections for 5-10 days, followed by 150 IU/kg (1.5 mg/kg) OD up to 6 months.

 

 

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

Novel bleeding prediction model in atrial fibrillation patients on new oral anticoagulants

Heart
Article describes development of a risk score including 9 variables (e.g. male sex, anaemia, thrombocytopaenia, concurrent antiplatelet therapy, hypertension, prior major bleeding, risk factors for a fall, low cholesterol level and low eGFR), requiring further validation.

 

 

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

Long-term risk for major bleeding during extended oral anticoagulant therapy for first unprovoked venous thromboembolism: A Systematic Review and Meta-analysis

Annals of Internal Medicine
Review (14 RCTs;13 cohort studies; n=17,202) found long-term risks & consequences of anticoagulant-related major bleeding are considerable in this population (incidence/100 person-years =1.74 events with VKAs & 1.12 events with DOACs;5-year cumulative incidence with VKAs was 6.3%.

 

Utilization and long-term persistence of direct oral anticoagulants among patients with nonvalvular atrial fibrillation and liver disease

British Journal of Clinical Pharmacology
UK study (n=3167; 71% on DOACs; 29% vitamin K antagonists [VKA]) found initiators of DOACs were more likely to have prior ischemic stroke (OR 1.44), less likely to have used antiplatelets (OR 0.66) and more likely to persist with treatment at 5 years vs VKAs (31% vs 9%).

 

 

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

Effects of Antiplatelet Therapy After Stroke Caused by Intracerebral Hemorrhage: Extended Follow-up of the RESTART Randomized Clinical Trial

JAMA Neurology
UK RCT (n=537; median 3-year follow-up), found no difference in recurrent intracerebral haemorrhage (8.2% with antiplatelet therapy [AT] vs 9.3% without AT; adjusted HR, 0.87; 95% CI, 0.49-1.55; P = 0.64) or major vascular events (26.8 vs 32.5%; 0.79; 0.58-1.08; P = 0.14).

 

Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage in the UK: a randomised, open-label, assessor-masked, pilot-phase, non-inferiority trial

The Lancet Neurology
SoSTART RCT (n=218) did not confirm non-inferiority of starting oral anticoagulation (OAC) vs avoiding OAC for recurrent intracranial haemorrhage: 8% vs 4%; adjusted HR 2.42; 95% CI 0.72–8.09; p=0.152) with no difference in serious adverse events (17% vs 15%).

 

De-Escalation of Dual Antiplatelet Therapy in Patients WithAcute Coronary Syndromes

Journal of the American College of Cardiology
In analysis (15 RCTs;n=55,798), DAPT with aspirin & de-escalation from standard-dose potent P2Y12inhibitor (ticagrelor or prasugrel[PG]) to clopidogrel or low-dose PG 1 month after PCI was linked to fewer bleeding events vs. other DAPT strategies & no increase in ischaemic events.

 

Utility of Intravenous Alteplase Prior to Endovascular Stroke Treatment: A Systematic Review and Meta-analysis of RCTs

Neurology
Review (3 studies, n=1092) detected no differences in functional outcomes at 3 months with direct endovascular treatment compared to combination of endovascular treatment preceded by IV thrombolysis in patients with an acute large vessel occlusion.

 

 

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 (21 RCTs [3 new]; n=2401) found low‐certainty evidence suggesting thrombolytics may reduce death following acute PE compared with heparin and may be helpful in reducing the recurrence of pulmonary emboli, but may cause more major and minor haemorrhagic events.

 

Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk

New England Journal of Medicine
In people at high risk of bleeding after implantation of drug-eluting stent (n=4434), 1 month of dual antiplatelet therapy was non-inferior to continuation for ≥2 additional months with regard to occurrence of net adverse clinical events and major adverse cardiac/cerebral events.

 

Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR

New England Journal of Medicine
In this study (n=1426), edoxaban was non-inferior to vitamin K antagonists in terms of the primary composite endpoint (death, MI, ischaemic stroke, systemic thromboembolism, valve thrombosis, major bleeding) in people with AF after successful TAVR (HR 1.05; 95% 0.85-1.31; p=0.01).

 

2021 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines for the management of valvular heart disease

European Heart Journal
This updated guideline considers new evidence in this area, leading to a number of new recommendations, including use of anti-thrombotic therapies in patients with surgical or transcatheter bioprostheses for bridging during perioperative periods and over the long term.

 

 

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: Xarelto (rivaroxaban) 1mg/ml granules for oral suspension and film coated tablets – all strengths

electronic Medicines compendium
SPC updated to include warning that patients with cancer may be at higher risk of bleeding and thrombosis and the individual benefit should be weighed against risk for bleeding in patients with active cancer dependent on tumour location, antineoplastic therapy & stage of disease.

 

Ticagrelor monotherapy in patients with chronic kidney disease undergoing percutaneous coronary intervention: TWILIGHT-CKD

European Heart Journal
This prespecified sub-analysis of the TWILIGHT trial (n=6835) found among CKD patients undergoing PCI, ticagrelor monotherapy reduced the risk of bleeding vs ticagrelor plus aspirin (4.6% vs. 9.0%; ) [HR 0.50, 95% CI 0.31–0.80)] without a significant increase in ischaemic events.

 

Compression stockings for preventing deep vein thrombosis in airline passengers

Cochrane Database of Systematic Reviews
Review (12 RCTs; n=2918) found high‐certainty evidence of a substantial reduction in incidence of symptomless DVT, low‐certainty evidence that leg oedema is reduced, and moderate‐certainty evidence that superficial vein thrombosis may also be reduced, with compression stockings.

 

Heparin Resistance — Clinical Perspectives and Management Strategies

New England Journal of Medicine
This review discusses inhibition of coagulation, identification of heparin resistance, diagnostic tests, mechanisms of resistance, testing and treatment.

 

Low-dose rivaroxaban plus aspirin in older patients with peripheral artery disease undergoing acute limb revascularization: insights from the VOYAGER PAD trial

European Heart Journal
Analysis of VOYAGER trial (n=6564) found the efficacy and safety outcomes for rivaroxaban in peripheral artery disease (PAD) were consistent across patient age. Authors state these results suggest rivaroxaban plus aspirin can be considered for PAD regardless of age.

 

 

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

Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants

Heart
Danish registry study (n=98,376) found an increased risk of gastrointestinal bleeding in patients exposed to oral glucocorticoids and DOACs vs those only on DOACs (60 day risk of bleed = 0.71% vs 0.38%, RR 1.89, 95%CI 1.43-2.36).

 

Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period

Cochrane Database of Systematic Reviews
Review (29 trials; n=3839) found evidence is very uncertain about benefits/harms of VTE thromboprophylaxis in women during pregnancy and the early postnatal period at increased risk of VTE. As large definitive trials unlikely to be funded, high‐quality registry data are important.

 

Venous thromboembolism in adults- quality standard (QS201)

National Institute for Health and Care Excellence
This updates and replaces quality standards on venous thromboembolism in adults: reducing the risk in hospital (published June 2010), and venous thromboembolism in adults: diagnosis and management (published March 2013).

 

 

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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