Determinants for under- and overdosing of direct oral anticoagulants and physicians' implementation of clinical pharmacists' recommendations

British Journal of Clinical Pharmacology
Study of 1688 patients with AF on DOACs reports inappropriate prescribing in 16.9% with underdosing more prevalent vs overdosing (9.7% vs 6.9%). Pharmacist advice was accepted in 72% of cases. 51.4% of advices were for underdosing 45.8% for overdosing & 2.8% for contraindications.


Mortality Benefit of Rivaroxaban Plus Aspirin in Patients With Chronic Coronary or Peripheral Artery Disease

Journal of the American College of Cardiology
After median 23 months follow up, COMPASS trial (n=27,395) found combination of rivaroxaban and aspirin, vs aspirin alone, reduced overall (3.4% vs 4.1%; HR: 0.82; 95% CI: 0.71-0.96) and CV mortality (1.7% vs 2.2%; HR: 0.78; 95% CI: 0.64-0.96) but not non-CV death.


Antiplatelet therapy in patients with conservatively managed spontaneous coronary artery dissection from the multicentre DISCO registry

European Heart Journal
This study (n=199) found dual antiplatelet therapy (DAPT) was associated with a higher rate of major adverse cardiovascular events compared to single antiplatelet therapy (SAPT) after 1 year-follow up (18.9% vs. 6%) [HR 2.62; 95% CI 1.22–5.61; P=0.013].


Non-vitamin K antagonist oral anticoagulants, proton pump inhibitors and gastrointestinal bleeds

This cohort study (n=164,290) found PPI use was linked to lower rate of upper GI bleed (UGIB) rates (IRR: 0.75; 95% CI: 0.59 to 0.95). PPI's had the largest protective effect in the patient group with a HAS-BLED score of ≥3 (IPW IRR 0.51; 95% CI: 0.35 to 0.77).


Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

New England Journal of Medicine
RCT was stopped when prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data for 1098 patients found no significant difference in organ support–free days (1 vs 4 for usual-care thromboprophylaxis) or in percentage who survived to hospital discharge.


Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

New England Journal of Medicine
RCT (n=2219) found therapeutic-dose anticoagulation with heparin increased probability (98.6%; OR 1.27; 95% CI, 1.03-1.58) of survival to hospital discharge vs. usual-care thromboprophylaxis, with reduced use of CV or respiratory organ support.


Switching of oral anticoagulants in patients with non-valvular atrial fibrillation: A narrative review

British Journal of Clinical Pharmacology
Review of 39 articles published after 2013 noted decision to switch was often related to safety issues (usually bleeding), poor anticoagulation control and ease-of-use. Limited data suggest switching did not have significant impact on risk of stroke and other thrombotic outcomes.


Management of acute coronary syndromes in older adults

European Heart Journal
Review focuses on evidence-based interventional and pharmacological approaches, noting that more powerful strategies of antithrombotic therapy for secondary prevention have been linked to increased bleeding events and no benefit in terms of mortality reduction in older adults.


Association of Oral Anticoagulation With Stroke in Atrial Fibrillation or Heart Failure: A Comparative Meta-Analysis

Review (21 trials; n=29,198) found the association of oral anticoagulation with all stroke (vs control) was consistent for AF (OR 0.51; 95% CI 0.42–0.63]) and heart failure with reduced ejection fraction (0.61; 0.47–0.79); the relative association with other outcomes was similar.



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:

Predictors, time course, and outcomes of persistence patterns in oral anticoagulation for non-valvular atrial fibrillation: a Dutch Nationwide Cohort Study

European Heart Journal
Study (n=93 048) found at least 25% of pts were non-persistent with oral anticoagulants (OACs) within 4 years, resulting in increased risk of composite of ischaemic stroke (IS) and IS-related death (HR 1.79, 95% CI 1.49–2.15) and IS (1.58; 1.29–1.93) vs persistence with OACs.


Frailty and clinical outcomes of direct oral anticoagulants versus warfarin in older adults with atrial fibrillation: A cohort study

Annals of Internal Medicine
In this analysis of Medicare claims data, only apixaban was consistently associated with lower rates of the composite end point of death, ischaemic stroke, and major bleeding than warfarin across all frailty levels (n=218,738; HR, 0.68 [CI, 0.65 to 0.72].


Abelacimab for Prevention of Venous Thromboembolism

New England Journal of Medicine
This trial (n=412) found treatment with abelacimab, a monoclonal antibody that binds to factor XI, was linked to a lower rate of VTE occurrence compared to enoxaparin; 13%, 5% and 4% in the 30mg, 75mg and 150mg abelacimab groups vs 22%, respectively (p<0.001).


Antithrombotic therapies in aortic and peripheral arterial diseases in 2021: a consensus document from the ESC working group on aorta and peripheral vascular diseases, the ESC working group on thrombosis, and the ESC working group on cardiovascular pharmacotherapy

European Heart Journal
This consensus document provides guidance on antithrombotic therapy according to arterial disease localisations and clinical presentation and highlights that multidisciplinary team discussions are important in patients with uncertain ischaemic/bleeding balance.


Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: A multi-center, open-label, randomized controlled trial

Journal of Thrombosis and Haemastasis
RCT of 176 hospitalized adults with severe COVID-19, found no difference in all-cause mortality at 30 days for standard prophylactic dose and intermediate dose enoxaparin (21% vs 15%; HR, 0.67; 95% CI 0.33–1.37; P = 0.31), or rates of arterial or venous thrombosis.


COVID-19 rapid guideline: vaccine-induced immune thrombocytopenia and thrombosis (VITT)- guidance (NG200)

National Institute for Health and Care Excellence
This guideline was produced to support clinicians to diagnose and manage this newly recognised syndrome for which there is limited evidence available to inform clinical management. Identification and management of VITT is evolving quickly as the case definition becomes clearer.


Risk assessment models for venous thromboembolism in hospitalised adult patients: a systematic review

BMJ Open
Analysis of 51 studies (24 unique risk assessment models [RAMs]) found estimates for sensitivity and specificity were highly variable; results suggest RAMs have generally weak predictive accuracy for VTE, with insufficient evidence to recommend the use of any particular model.


Comparative table of low molecular weight heparins and fondaparinux

Specialist Pharmacy Service
This comparative table of low molecular weight heparins and fondaparinux has been compiled to aid product selection should there be a need to switch product in the event of a shortage.


Tinzaparin sodium (10,000 IU/ml) 3,500 units in 0.35ml and 4,500 units in 0.45ml pre-filled syringes - Supply Disruption

Medicines and Healthcare products Regulatory Agency
These pre-filled syringes will be unavailable between middle of October 2021 and January 2022 (date TBC). All other presentations of tinzaparin remain unaffected by this supply disruption. This alert contains further information and action for providers.



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:

Network Meta-Analysis of Ticagrelor for Stroke Prevention in Patients at High Risk for Cardiovascular or Cerebrovascular Events

Review (26 RCTs; n= 124 495) found compared to controls, addition of aspirin to ticagrelor reduced risk of ischemic stroke (RR, 0.80; 95% CI, 0.71–0.89 vs 0.88; 0.77–1.00 for ticagrelor monotherapy; P=0.05) but was associated with increased bleeding risk.


Trends in the pharmacological management of atrial fibrillation in UK general practice 2008–2018

There was increase in patients with AF appropriately prescribed anticoagulants (from 45.3 to 71.1%) following NICE and ESC guidelines, which correlates with improvements in mortality and stroke outcomes. Beta-blockers appear increasingly favoured over digoxin for rate control.


Efficacy and Safety of Ticagrelor and Aspirin in Patients With Moderate Ischemic Stroke: An Exploratory Analysis of the THALES Randomized Clinical Trial

JAMA Neurology
Sub-group analysis (n= 9983) ticagrelor plus aspirin showed similar efficacy and safety vs aspirin alone in patients presenting with moderate acute ischemic stroke and those presenting with less severe ischemic cerebrovascular events.


Aspirin versus P2Y12 inhibitors with anticoagulation therapy for atrial fibrillation

Study (n= 1075 of which ~60% on PPI) found no significant differences in CV and bleeding events in patients with AF and stable CAD taking rivaroxaban with P2Y12 inhibitors or aspirin in chronic phase (efficacy HR: 1.31; 95% CI 0.88 to 1.94; safety HR: 0.79; 95% CI 0.43 to 1.47).


Inappropriate anticoagulation of patients with a mechanical heart valve

Medicines and Healthcare products Regulatory Agency
This alert asks GPs and other NHS providers of anticoagulation services to identify patients with a record of a mechanical heart valve and receiving a DOAC, and to urgently review these patients to ensure they are on the most appropriate anticoagulation therapy and monitoring.



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:

FDA approves dabigatran etexilate oral pellets to treat children 3 months to less than 12 years old with venous thromboembolism

US Food and Drug Administration
Approval is for oral pellets to treat children age 3 months to <12 years and for capsules to treat patients age ≥8 years, with VTE after parenteral anticoagulation for ≥5 days, and also for prevention of recurrent clots in those who have completed treatment for their first VTE.


Comparison of effectiveness and safety between ticagrelor and clopidogrel in patients with acute coronary syndrome and on dialysis in Taiwan

British Journal of Clinical Pharmacology
Study (n=2185) of dialysis patients with ACS found at 12 months, ticagrelor group had higher risk for major adverse CV event (aHR 1.29; 95% CI 1.16–1.44) and also higher risk of major bleeding event vs clopidogrel group (sHR 1.49; 95% CI 1.34–1.65).


Pulmonary embolism in patients with COVID-19: incidence, risk factors, clinical characteristics, and outcome

European Heart Journal
Spanish retrospective study identified 368 PE in 74,814 patients with COVID-19 attending A+E (~ 0.5%), the incidence of which is ~ninefold higher than in the general (non-COVID-19) population. It notes that mortality is higher in COVID-19 than in non-COVID-19 patients with PE.


Number needed to treat for net effect of anticoagulation in atrial fibrillation: Real-World vs. Clinical Trial Evidence

British Journal of Clinical Pharmacology
Post-hoc analysis demonstrated potential clinical applicability of the NNT for net benefit approach; the Calculator of Absolute Stroke Risk was used to show that the NNTnet of anticoagulation therapy at 1-year was 34 in a real-world cohort and 46 in a clinical trial population.


Ticagrelor or Prasugrel for Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention: A Prespecified Subgroup Analysis of a Randomized Clinical Trial

JAMA Cardiology
Analysis (n=3024) found incidence of primary composite end point (all-cause death, MI or stroke) at 12 months occurred less frequently in prasugrel vs. ticagrelor group (120 [7.1%] vs 162 [9.8%], respectively; HR 1.41; 95% CI, 1.11-1.78; p= 0.005); bleeding events were comparable.


XIENCE stent receives FDA approval for use of only one-month dual antiplatelet therapy (DAPT) in (HBR) high bleeding risk patients

Biospace Inc.
Patients who receive stents are typically on DAPT for 6 to 12 months but may cause bleeding in HBR patients. According to Abbott, the XIENCE 28 and XIENCE 904 studies showed that DAPT can be safely discontinued early (as short as 28 days) with no increased risk in adverse events.


Cerebral Venous Thrombosis

New England Journal of Medicine
This review covers diagnosis, based on clinical and imaging features, and treatments that have become available since the subject was last reviewed, in light of current interest, due to rare cases associated with certain of the Covid-19 vaccines.


DTB select: Aspirin and gastrointestinal bleeding risk in older people

Drug and Therapeutics Bulletin
Summary and context is provided for an analysis of data from the ASPREE study, which found the 5-year risk of a gastrointestinal bleed in older people taking low-dose aspirin (100mg) ranged from 0.40% in those aged 70 years to 5% in those aged 80 years with multiple risk 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:




The association between increasing oral anticoagulant prescribing and atrial fibrillation related stroke in Ireland

British Journal of Clinical Pharmacology
Registry study of data between 2005 and 2018 found an increase in the use of oral anticoagulants of 94%, mainly fuelled by use of DOACs. Ischaemic stroke rates did not reduce, however the percentage of patients with a stroke diagnosed with AF decreased between 2013 and 2018.


P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials

British Medical Journal
Meta-analysis (6 trials;n=24 096) found P2Y12 inhibitor monotherapy linked to similar risk of death, MI, or stroke, with evidence this may be modified by sex & lower bleeding risk vs. dual antiplatelet therapy (primary outcome occurred in 2.94 vs. 3.36%;HR 0.90, 95% CI 0.77-1.08).



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:

Updated COVID-19 vaccination guidance: blood clotting information for healthcare professionals

Public Health England
This guidance has been updated to include antiphospholipid syndrome, interchangeability of COVID-19 vaccines, samples required for whole genome sequencing and the latest MHRA data.


Postoperative low molecular weight heparin bridging treatment for patients at high risk of arterial thromboembolism (PERIOP2): double blind randomised controlled trial

British Medical Journal
RCT (n=1471, Canada & India) found that in patients with AF or mechanical heart valves who had warfarin interrupted for a procedure, no significant benefit was found for postop dalteparin bridging to prevent major thromboembolism (occurred in 1.0% vs. 1.2% placebo within 90 days).



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:

Andexanet Alfa or Prothrombin Complex Concentrate for Factor Xa Inhibitor Reversal in Acute Major Bleeding : A Systematic Review and Meta-Analysis

Critical Care Medicine
Review of 21 studies (n=1716) found haemostatic effectiveness of 71% & 76% for andexanet & prothrombin complex concentrate respectively at 24hrs. Mortality rate was 23.3% & 15.8%. Analysis for controlling confounders did not demonstrate significant differences between treatments.


Effectiveness and safety among direct oral anticoagulants in nonvalvular atrial fibrillation: A multi-database cohort study with meta-analysis

British Journal of Clinical Pharmacology
Review of cohort studies (total n=227,679) found apixaban had a lower rate of ischaemic stroke or thromboembolism (HR 0.85, 95%CI 0.74-0.99) and major bleeding (0.61, 0.53-0.70) vs rivaroxaban. There were no significant differences in risk between apixaban and dabigatran.


Which is the best model to assess risk for venous thromboembolism in hospitalised patients?

British Medical Journal
Practice article notes risk assessment models (RAMs) help clinicians decide who should be offered pharmacological thromboprophylaxis, but variation exists in their composition of risk factors and thresholds for high and low risk, and there is uncertainty over the most optimal RAM.



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:

Systematic review of machine learning models for personalised dosing of heparin

British Journal of Clinical Pharmacology
Review concluded that there are limited studies of machine learning models for unfractionated heparin dosing, and none report a model ready for routine clinical use. Studies are low quality, inadequately report study factors and lack of external validation and impact analysis.


Total Ischemic Event Reduction with Rivaroxaban after Peripheral Arterial Revascularization in the VOYAGER PAD Trial

American Journal of Cardiology
Sub-analysis (n=6564) found rivaroxaban plus aspirin reduced total primary events (acute limb ischemia, major amputation, MI, ischemic stroke, or CV death; HR 0.86,95% CI 0.75-0.98; p=0.02) and peripheral revascularizations and VTE (0.86; 0.79-0.95; p=0.003) vs aspirin alone.


Single direct oral anticoagulant therapy in stable patients with atrial fibrillation beyond 1 year after coronary stent implantation

Korean study (n=4294; 94% with drug-eluting coronary stents) showed similar efficacy in preventing ischaemic events in the DOAC monotherapy vs DOAC plus antiplatelet group (HR 0.828, 95% CI 0.660 to 1.038) with lower risk of major bleeding (HR 0.690, 95% CI 0.481 to 0.989).


Sex Differences Among Patients With High Risk Receiving Ticagrelor With or Without Aspirin After Percutaneous Coronary Intervention: A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial

JAMA Cardiology
Analysis (n= 7119) found women had a higher bleeding risk vs men, which was mostly attributable to baseline differences, whereas ischemic events were similar. Benefits of early aspirin withdrawal with continuation of ticagrelor were generally comparable in women and men.


Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease

New England Journal of Medicine
Open-label pragmatic trial found no differences in cardiovascular events (event rate 7.28% vs 7.51%; HR 1.02; 95% CI 0.91 to 1.14) or major bleeding (0.63% vs 0.60%; HR 1.18; 95% CI, 0.79 to 1.77) in patients with CVD assigned to 81 mg or 325 mg of aspirin daily, respectively.


Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial

The Lancet
Korean study found clopidogrel vs aspirin monotherapy significantly reduced composite of all-cause death, non-fatal MI, stroke, readmission due to acute coronary syndrome, and bleeding (n=5530; 24 month follow up; event rate 5.7% vs 7.7%; HR 0.73; 95% CI 0.59–0.90).



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:

Sex‐influence on the time in therapeutic range (TTR) during oral anticoagulation with coumarin derivatives: systematic review and meta‐analysis

British Journal of Clinical Pharmacology
Review of 22 studies (n=110 to 104,505 of which 183,612 women [45%]) found an association between female sex and worse oral anticoagulation control (OR for TTR=0.87; 95% CI=0.78-0.96; p=0.006, based on meta-analysis of 15 studies).


Anticoagulant Use for Atrial Fibrillation Among Persons With Advanced Dementia at the End of Life

JAMA Internal Medicine
Study of 15,217 nursing home residents with AF and advanced dementia in US found ~30% remained on anticoagulation (AC) in last 6 months of life, underscoring fact that whilst there is well-defined threshold for starting AC for AF, there is no clear standard for stopping it.


Tranexamic acid and bleeding in patients treated with non-vitamin K oral anticoagulants undergoing dental extraction: The EXTRACT-NOAC randomized clinical trial

PLOS Medicine
RCT (n=218) found use of 10% tranexamic acid mouthwash does not seem to reduce rate of periprocedural or early postop oral bleeding (OB) up to day 7 vs. placebo (occurred in 26.4% vs 28.6%,respectively), but appears to reduce delayed bleeds & postop OB if multiple teeth extracted.


Venous thromboembolism

The Lancet
This Seminar focuses on recent (past 5 years) advances in epidemiology, pathophysiology, diagnosis, treatment, and prevention of deep vein thrombosis of the legs and pulmonary embolism. Future directions are also discussed.


Andexanet alfa for reversing anticoagulation from apixaban or rivaroxaban - guidance (TA697)

National Institute for Health and Care Excellence
Andexanet alfa is recommended as an option for reversing anticoagulation from apixaban or rivaroxaban in adults with life-threatening or uncontrolled bleeding, only if requirements met as outlined in guidance.


Effectiveness and safety of oral anticoagulants in elderly patients with atrial fibrillation

Nationwide cohort study of patients ≥75 years (n=30,401) found that when initiating oral anticoagulation for AF, standard and reduced dose DOACs had similar risks of stroke/systemic embolism as warfarin and lower or similar risks 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:

Prior use of therapeutic anticoagulation does not protect against COVID‐19 related clinical outcomes in hospitalized patients: a propensity score‐matched cohort study

British Journal of Clinical Pharmacology
Retrospective Dutch study (n=1154) found no associations between prior therapeutic anticoagulation use (16% of population) and mortality (RR 1.02; 95% CI; 0.80‐1.30) or length of hospital stay (7.0 vs 7.0 days, p=0.69), except lower risk of pulmonary embolism (0.19; 0.05‐0.80).


Atrial fibrillation: diagnosis and management- Updated guidance (NG196)

National Institute for Health and Care Excellence
Updates include use of tools to calculate risk of bleeding when considering use of anticoagulants, role of newer anti-clotting drugs, and use of treatments that aim to destroy or isolate the abnormal sources of electrical impulses in the heart that may be driving AF (ablation).


Is there a circannual variation in the anticoagulation control of warfarin?

European Journal of Hospital Pharmacy
This retrospective study (n=204) found no significant intra-individual differences in mean time in therapeutic range. Patients with poor anticoagulation control, high INR variability and high warfarin sensitivity index was not significantly different between the seasons.


Genotype‐guided antiplatelet treatment versus conventional therapy: A systematic review and meta‐analysis

British Journal of Clinical Pharmacology
Review of 16 studies (n=10,561, 8 studies were RCTs) found lower rates of major adverse cardiovascular events (RR 0.56, 95%CI 0.44‐0.73), stent thrombosis (0.40, 0.24‐0.67) and myocardial infarction (0.45, 0.35‐0.58) with genotype‐guided vs conventional treatment.


Tranexamic Acid for the Prevention of Blood Loss after Cesarean Delivery

New England Journal of Medicine
RCT (n=4551) found tranexamic acid resulted in a significantly lower incidence (LI) of calculated estimated blood loss >1000ml or red-cell transfusion by day 2 vs. placebo (26.7% vs. 31.6%, risk ratio, 0.84; 95% CI, 0.75-0.94; p=0.003), but not LI of haemorrhage-related outcomes.


Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study

British Medical Journal
Study (n=281,264) notes increased rates of VTE events (standardised morbidity ratio 1.97; 95% CI, 1.50 to 2.54 and 11 [5.6 to 17.0] excess events per 100 000 vaccinations) including cerebral venous thrombosis, but the absolute risks were small.



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:

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