Optimal route for administering tranexamic acid in primary unilateral total hip arthroplasty: Results from a multicenter cohort study

British Journal of Clinical Pharmacology

Data collection from 7,667 total hip arthroplasties found that IV, topical, and combined tranexamic acid all showed a significantly lower incidence of DVT than controls (0.08% vs 0.47%, p=0.001) as well as a lower rate of other complications (0.34% vs 0.67%, p=0.044).

Atrial fibrillation groups lobby patients to overturn screening committee decision

British Medical Journal

Article reports that patients' groups with funding from drug companies with vested interests are putting pressure on the National Screening Committee to overturn its decision not to recommend an AF screening programme. Doctors are concerned the campaign goes against the evidence.

Revised SPC: Eliquis (apixaban) film-coated tablets

electronic Medicines compendium

The SPC has been updated to include information about dosing in patients undergoing interventions (e.g. catheter ablation) for non-valvular atrial fibrillation.

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 Between Warfarin Control Metrics and Atrial Fibrillation Outcomes in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation

JAMA Cardiology

In this cohort study of 10,137 patients with atrial fibrillation, historical INR variance was associated with future bleeding events, but not with future stroke risk, suggesting caution when using historical INR to assess likelihood of bleeding or thrombotic events.

Antithrombotic doses: clinical observations from published clinical trials

British Journal of Clinical Pharmacology

This review discusses uncertainties around optimal doses of antithrombotic agents e.g. data from RCTs show aspirin is effective at doses below 75 mg daily and direct oral anticoagulants reduce risk of stroke in AF patients at doses 1/4 of those currently recommended.

Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent: systematic review and network meta-analysis

British Medical Journal

Review found long vs short term (>12 vs <6 months) DAPT resulted in higher rates of major bleeding (OR 1.78, 95% CI 1.27 to 2.49) and non-cardiac death (1.63, 1.03 to 2.59); standard term (12 months) DAPT was associated with higher rates of any bleeding (1.39, 1.01 to 1.92).

A Practical Approach to Low-Dose Aspirin for Primary Prevention

Journal of the American Medical Association

This article discusses use of aspirin for primary prevention of atherosclerotic cardiovascular disease in the context of 3 large trials demonstrating bleeding risks comparable with benefits, and proposes a practical approach to initiate, continue, or discontinue aspirin.

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

Extended Anticoagulation for VTE: A Systematic Review and Meta-Analysis

Chest

Review of 16 studies (n=12,458) found DOACs linked to decrease in overall (risk ratio 0.48;95% CI;0.27-0.86;p=0.01) and VTE-related (0.36;0.15-0.89;p=0.03) mortality whereas VKAs were not. Both similarly prevented recurrent VTE but only VKAs linked to increased major bleeding risk.

Time Course for Benefit and Risk of Clopidogrel and Aspirin after Acute Transient Ischemic Attack and Minor Ischemic Stroke: A Secondary Analysis from the POINT Randomized Trial

Circulation

Secondary analysis of POINT (n=4,881) noted benefit of clopidogrel+aspirin occurs predominantly within first 21 days and outweighs low, but ongoing risk of major haemorrhage suggesting limiting use to 21 days may maximize benefit/reduce risk after TIA/minor ischaemic stroke.

Conference report: Increasing Dietary Vitamin K Intake Stabilizes Anticoagulation Therapy in Warfarin-Treated Patients with a History of Instability- A 24-week Randomized Controlled Trial

American Society for Nutrition

RCT (n=49) found increasing dietary vitamin K intakes resulted in greater proportion patients with %TTR ˃70% over assessment period. (50 % who increased intake by ≥150 µd/day through specific food choices met criteria vs. 19% control [general dietary information] group; p=0.026.

A systematic review of patient‐reported outcomes associated with the use of direct‐acting oral anticoagulants

British Journal of Clinical Pharmacology

Review of 21 studies reports patients appear to prefer treatment with DOACs vs warfarin, as shown by the higher quality of life, satisfaction and adherence described in the studies. However, heterogeneity in the analysed studies does not allow firm conclusions.

A comprehensive analysis of the effects of rivaroxaban on stroke or transient ischaemic attack in patients with heart failure, coronary artery disease, and sinus rhythm: the COMMANDER HF trial

European Heart Journal

In this post hoc analysis (n=5022), rivaroxaban significantly reduced the primary neurological endpoint of all-cause stroke or TIA compared with placebo by 32% (2.4% vs. 3.5%; 1.29 events vs. 1.90 events per 100 patient-years; HR 0.68; P = 0.02).

Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI The STOPDAPT-2 Randomized Clinical Trial

Journal of the American Medical Association

This RCT (n=2974) reports 1-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT v 3.70% with 12-month DAPT (difference −1.34%; HR 0.64, meeting criteria for noninferiority (P<0.001) and superiority (P=0.04).

Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention The SMART-CHOICE Randomized Clinical Trial

Journal of the American Medical Association

In this RCT (n=2912) P2Y12 inhibitor monotherapy after 3-month duration of DAPT resulted in a noninferior rate of major cardiovascular events (all-cause death, MI, and stroke) vs prolonged DAPT at 12 months (2.9% vs 2.5%; difference 0.4%; P=0.007 for non-inferiority).

Revised SPC: Xarelto (rivaroxaban) film-coated tablets

electronic Medicines compendium

The SPC has been updated in line with PRAC recommendations to advise DOACs, including rivaroxaban, are not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome, in particular for patients that are triple positive.

Coagulation Testing in Patients Taking Direct Oral Anticoagulants: A Teachable Moment

JAMA Internal Medicine

This Teachable Moment examines the case of a man taking a direct oral anticoagulant (DOAC) who received a high INR test result during a visit to the emergency department, and highlights that INR is an unreliable measure of therapeutic anticoagulation in patients taking DOACs.

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

Direct-acting oral anticoagulants (DOACs): increased risk of recurrent thrombotic events in patients with antiphospholipid syndrome

Medicines and Healthcare products Regulatory Agency

MHRA advises that DOACs are not recommended in patients with antiphospholipid syndrome, particularly high-risk patients (those who test positive for all 3 antiphospholipid tests — lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2 glycoprotein I antibodies).

Safety and Efficacy of Antithrombotic Strategies in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Network Meta-analysis of Randomized Controlled Trials

JAMA Cardiology

Review of 4 RCTs (n = 10 026) found DOAC plus P2Y12 inhibitor was linked to less bleeding vs. vitamin K antagonists + dual antiplatelets; strategies omitting aspirin caused less bleeding without significant difference in major adverse CV event vs. strategies including aspirin.

Warfarin dose requirement in patients having severe thrombosis or thrombophilia

British Journal of Clinical Pharmacology

Study (n=50) found that currently the most used pharmacogenetics dosing algorithms (IWPC and Gage) underestimate the warfarin dose required for effective anticoagulation in thrombogenic young (age <50 years) patients, particularly those who are at the highest thrombotic risk.

Revised SPC: Brilique (ticagrelor) tablets

electronic Medicines compendium

Thrombotic thrombocytopenic purpura has been added as a potential adverse effect of treatment (frequency unknown).

Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial

Journal of the American College of Cardiology

Open-label RCT (n=3,799) found that ticagrelor did not significantly reduce the frequency of CV events vs clopidogrel when used after fibrinolytic therapy (combined outcome of CV mortality, MI or stroke = 6.7% vs 7.3% for ticagrelor vs clopidogrel, HR 0.93, 95% CI 0.73-1.18).

Oral anticoagulants in atrial fibrillation with valvular heart disease and bioprosthetic heart valves

European Heart Journal

Network meta-analysis (n=13,574) found that NOACs are superior, vs warfarin, in reducing stroke or systemic embolisation, MI and intracranial haemorrhage in AF and valvular heart disease. Analysis of 280 patients with AF and bioprosthetic heart valve showed similar outcomes.

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 SPCs: Eliquis (apixaban) film-coated tablets- all strengths

electronic Medicines compendium

SPCs highlight DOACs are not recommended for patients with history of thrombosis diagnosed with antiphospholipid syndrome, in particular, triple positive patients, where use of DOACs could be associated with increased rates of recurrent thrombotic events vs. vitamin K antagonists.

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 With or Without Aspirin in Patients with Heart Failure and Chronic Coronary or Peripheral Artery Disease: The COMPASS Trial

Circulation

Analysis of data from the COMPASS RCT (n=27,395) found that in heart failure patients specifically (5,902 patients), rivaroxaban plus aspirin was similarly superior to aspirin alone as per the overall trial population.

Evaluation of the Incidence of New-Onset Atrial Fibrillation After Aortic Valve Replacement

JAMA Internal Medicine

This population-based study reports new-onset AF was present in 50% of hospitalisations for transcatheter aortic valve implantation and aortic valve replacement. It advises shared patient-doctor decision making regarding potential need for anticoagulation after these procedures.

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 of direct oral factor Xa inhibitors compared with warfarin in patients with morbid obesity: a single-centre, retrospective analysis of chart data

The Lancet Haematology

Retrospective analysis of data evaluating safety and efficacy of direct oral anticoagulants and warfarin in 795 morbidly obese patients (BMI>40kg/m2) suggests concludes similar efficacy and safety of apixaban and rivaroxaban, compared to warfarin in patients with AF and VTE.

Randomized trial of ticagrelor vs. aspirin in patients after coronary artery bypass grafting: the TiCAB trial

European Heart Journal

Study (n=1,859) showed no significant difference in major cardiovascular events occurring in 9.7% ticagrelor patients vs. 8.2% aspirin patients [HR 1.19; 95% CI 0.87–1.62; p= 0.28]), or in major bleeding. RCT was terminated early & underpowered however due to recruitment issues.

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

Treatment and Long-Term Clinical Outcomes of Incidental Pulmonary Embolism in Patients With Cancer: An International Prospective Cohort Study

Journal of Clinical Oncology

Observational study of 695 patients with cancer and incidental diagnosis of PE suggests despite anticoagulant therapy, recurrent VTE occurred in 6% of patients, strengthening current guideline advice to treat incidental PE as symptomatic PE for at least 3 to 6 months.

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

The Lancet

RCT (n=537) reports 4% of participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage vs 9% allocated to avoid antiplatelet therapy (HR 0.51, p=0.060), whilst 7% and 9% of patients respectively experienced major haemorrhagic events (HR 0.71, p=0.27).

Defining High Bleeding Risk in Patients Undergoing Percutaneous Coronary Intervention: A Consensus Document From the Academic Research Consortium for High Bleeding Risk

Circulation

The consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data

The Lancet

Review of 3 RCTs (n=414) found that more patients given alteplase achieved excellent functional outcomes at 3 months vs placebo (36% vs 29%, OR 1.86, p=0.011). Intracerebral haemorrhage was more common with alteplase (5% vs 1%, OR 9.7, p=0.031).

Revised SPC@ Pradaxa (dabigatran etexilate mesilate) hard capsules (all strengths)

electronic Medicines compendium

Section 4.4 has been updated to include a warning regarding thromboembolic risk in patients with antiphospholipid syndrome.

Tofacitinib (Xeljanz▼): restriction of 10 mg twice-daily dose in patients at high risk of pulmonary embolism while safety review is ongoing

Medicines and Healthcare products Regulatory Agency

Following an increased risk of pulmonary embolism and overall mortality with tofacitinib 10 mg twice-daily in the study A3921133 rheumatoid arthritis study, a safety review has started and this dose (authorised for ulcerative colitis) is contraindicated in patients at high risk of VTE.

Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial

European Heart Journal

Study suggests that early discharge with continuation of rivaroxaban at home is safe and effective in certain low-risk patients with acute PE. Rate of symptomatic recurrent VTE or PE-related death within 3 months (primary outcome) occurred in 3 of 525 patients (0.6%; P <0.0001).

The rise and fall of aspirin in the primary prevention of cardiovascular disease

The Lancet

This narrative review discusses the role of aspirin in primary prevention of cardiovascular disease, contextualising data from historical and contemporary trials.

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

Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source

New England Journal of Medicine

RCT (n=5390) found that dabigatran was not superior to aspirin in preventing recurrent stroke, which occurred in 6.6% (4.1%/year) and 7.7% (4.8%/year), of patients, respectively. Incidence of major bleeding was not significantly greater in dabigatran group (1.7 vs. 1.4%).

Frequency of Intracranial Hemorrhage With Low-Dose Aspirin in Individuals Without Symptomatic Cardiovascular Disease: A Systematic Review and Meta-analysis

JAMA Neurology

Review of 13 RCTs (n=134,446) reports low-dose aspirin use among individuals without symptomatic cardiovascular disease (primary prevention) was associated with an increased risk of any intracranial bleeding especially in Asians, or people with a low body mass index.

Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions

Cochrane Database of Systematic Reviews

Review found 2 RCTs of 59 haemophiliacs only and reports beneficial effect of systemically administered tranexamic acid & epsilon aminocaproic acid in preventing postoperative bleeding. Definite efficacy in oral or dental procedures however is uncertain, due to limited evidence.

Less dementia and stroke in low-risk patients with atrial fibrillation taking oral anticoagulation

European Heart Journal

Study (n=91,254 with baseline CHA2DS2-VASc score ≤ 1) reports treatment with oral anticoagulation was associated with lower risk of dementia (subhazard ratio 0.6, 95% CI 0.48–0.81) in people aged >65 years; but the risk: benefit profile in <60 years is not so favourable.

Fragmin (dalteparin sodium) approved by FDA as first anticoagulant for children

PharmaTimes

The FDA has approved use in paediatric patients' ≥ 1 month of age to reduce recurrence of symptomatic venous thromboembolism. Approval was based on a single trial of 38 children with symptomatic deep vein thrombosis and pulmonary embolism treated with Fragmin for up to 3 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

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

Spontaneous haemorrhage on apixaban masquerading as obstructive cholangitis after heart surgery

European Heart Journal

This case was a 73-year-old with a presentation of obstructive cholangitis, likely secondary to migration of blood into the common bile duct as a complication of apixaban (2.5 mg 2×/day) 16 days post coronary artery bypass grafting.

Meta-Analysis of Direct-Acting Oral Anticoagulants Compared With Warfarin in Patients >75 Years of Age

American Journal of Cardiology

Review (5 studies, n=28,135) reports DOACs have superior efficacy compared to warfarin in reducing stroke or systemic embolisation (HR 0.76, 95% CI 0.67 to 0.86, p <0.01). Apixaban appeared to have the best benefit vs risk profile in this population.

Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke

New England Journal of Medicine

RCT (n=225) found use of alteplase between 4.5 and 9.0 hours after stroke onset resulted in higher proportion of patients with no/minor neurologic deficits vs placebo (35.4 vs.29.5%;risk ratio, 1.44; 95% CI, 1.01 to 2.06; p=0.04) but more cases of symptomatic cerebral haemorrhage.

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