Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin

Gastroenterology

RCT (n=17,598 followed up for median 3.01 years, with 53,152 patient-years of follow-up) found no statistically significant difference between pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% placebo group; OR 1.33; 95% CI, 1.01–1.75).

 

Increasing number of patients prescribed risky anticoagulant drug combinations

Pharmaceutical Journal

Statistics from the Medication Safety Dashboard show that between Sept 18 and Nov 18, there were more than 14,000 patients in England prescribed an NSAID with an anticoagulant and more than 30,000 patients prescribed an antiplatelet and anticoagulant without gastro-protection.

 

 

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

Venous thromboembolism prophylaxis strategies for people undergoing elective total knee replacement: a systematic review and network meta-analysis

The Lancet Haematology

Review (25 RCTs) found that vs no prophylaxis, rivaroxaban was most effective for prevention of DVT (RR 0.12; 95% CI 0.06–0.22). LMWH, vs no prophylaxis was found to be more effective for pulmonary embolism and best for major bleeding but these findings are highly uncertain.

 

Emicizumab as prophylaxis in people with severe congenital haemophilia A without factor VIII inhibitors (all ages)

NHS England

NHS England will commission emicizumab as prophylaxis in adults and children with severe congenital haemophilia A (defined as factor VIII level <1 IU/dL, or <1% of normal) without current inhibitors to prevent bleeding episodes.

 

Catheter Ablation for Atrial Fibrillation in 2019

Journal of the American Medical Association

This article reviews management approaches to atrial fibrillation (AF), including assessment of the need for anticoagulation, and controversies over the need for rhythm control and the role of catheter ablation for maintaining sinus rhythm and reducing AF-associated symptoms.

 

Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps: A Randomized Controlled Trial

Annals of Internal Medicine

RCT (n=184) found patients on continuous anticoagulants +cold snare polypectomy (CSP;without electrocautery) did not have increased incidence of polypectomy-related major bleeding, and procedure time and hospitalisation were shorter vs. periprocedural heparin bridging plus hot SP.

 

Effect of Recombinant Activated Coagulation Factor VII on Hemorrhage Expansion Among Patients With Spot Sign–Positive Acute Intracerebral Hemorrhage: The SPOTLIGHT and STOP-IT Randomized Clinical Trials

JAMA Neurology

RCTs included 69 patients and found that recombinant activated coagulation factor VII did not significantly improve radiographic or clinical outcomes vs. placebo among patients with spot sign–positive intracerebral haemorrhage treated a median of ~3 hours from stroke onset.

 

Outcomes Associated With Clopidogrel-Aspirin Use in Minor Stroke or Transient Ischemic Attack: A Pooled Analysis of Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and

JAMA Neurology

Analysis of POINT and CHANCE trials (n=10,051) found clopidogrel-aspirin treatment reduced risk of major ischaemic events at 90 days vs. aspirin, that appeared to be confined to the first 21 days (5.2% vs 7.8%; HR 0.66; 95% CI, 0.56-0.77; p <0 .001), but not from day 22 to day 90.

 

Prevention of Stroke in Atrial Fibrillation After Coronary Stenting: Systematic Review and Network Meta-Analysis

Stroke

Review of 3 RCTs and 15 observational studies (total n=23,478) found that DOACs were associated with less major bleeding and major cardiovascular adverse effects, but vitamin K antagonists were associated with decreased mortality and stroke.

 

 

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

Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies

The Lancet Haematology

Study (93 children) found that bodyweight adjusted rivaroxaban appears to be safe in children (no major bleeds, 4% rate of non-major bleed and no recurrent VTEs). Doses for <20kg showed low exposure, so the dosages for this group will be adjusted for the phase 3 study.

 

A Meta-Analysis of Aspirin for the Primary Prevention of Cardiovascular Diseases in the Context of Contemporary Preventive Strategies

American Journal of Medicine

Analysis of 14 RCTs(n=164,751) found aspirin decreases MI risk at expense of increased risks for major bleeding (BD) and haemorrhagic stroke. With contemporary aggressive preventive strategies, effect on MI risk seems to be much attenuated whereas its harmful effects on BD remain.

 

NIHR Signal: On balance, antiplatelet drugs may be restarted for stroke survivors who have bled into the brain

National Institute for Health Research

Expert commentary is provided of UK trial of 537 adults (RESTART) on antiplatelets before intracerebral haemorrhage, which found no material difference in risk of further bleeding or occlusive vascular event if they restarted on the drugs when feasible.

 

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

 

NIHR Signal: Reminders to assess clotting risk increase the use of preventive measures

National Institute for Health Research

Expert commentary is provided for a review of 13 RCTs (n=35,997) which found that alert based interventions increased the proportion of patients who received mechanical or drug prophylaxis vs standard care. Unfortunately, trial data are lacking on multifaceted interventions.

 

Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis

The Lancet Neurology

Scottish cohort study (n=300) found antithrombotic therapy linked to lower risk of subsequent intracranial haemorrhage (ICH) or focal neurological deficit. Meta-analysis of 6 cohort studies (n=1342) also noted lower ICH risk (3 vs. 14%; IRR 0.25; 95% CI,0.13–0.51;p<0.0001).

 

Meta-Analysis of Oral Anticoagulant Monotherapy as an Antithrombotic Strategy in Patients With Stable Coronary Artery Disease and Nonvalvular Atrial Fibrillation

American Journal of Cardiology

Analysis of 6 trials (n=8855) found no significant difference in major adverse CV event in patients on oral anticoagulant (OAC) plus single antiplatelet therapy (SAPT) vs. OAC monotherapy. OAC plus SAPT was linked to higher risk of major bleeding (HR 1.61; 95% CI 1.38-1.87).

 

Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant

JAMA Internal Medicine

Cohort study (n=3007) followed up post-operatively for 30 days suggests DOAC therapy interruption without heparin bridging or coagulation function testing before elective surgery were associated with low rates of major bleeding (<2%) and arterial thromboembolism.

 

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update

Journal of Clinical Oncology

This updated guideline now recommends thromboprophylaxis with apixaban, rivaroxaban, or low molecular weight heparin to selected high-risk outpatients with cancer, whilst rivaroxaban and edoxaban have been added as options for VTE treatment.

 

Thromboembolic events around the time of cardioversion for atrial fibrillation in patients receiving antiplatelet treatment in the ACTIVE trials

European Heart Journal

Study (n=962) found that thromboembolic risk increased in 30 days before cardioversion and persisted until 30 days post-cardioversion (0.47% and 0.96%, respectively; HR 2.2, 95% CI 0.7–7.1). Authors suggest that this increased risk may not be entirely causal.

 

 

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) tablets

electronic Medicines compendium

SPC now advises that rivaroxaban should not be used for thromboprophylaxis in patients having recently undergone transcatheter aortic valve replacement as the safety and efficacy have not been studied in this population.

 

Educational Risk Minimisation Materials to help reduce the risk associated with the use of combined hormonal contraceptives (CHCs)

Bayer

Bayer has published a checklist for prescribers, a Q&A on important information for women and a summary of important information about risk of blood clots with combined hormonal contraceptives, for all Bayer CHC products.

 

 

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

Clinical Effectiveness of Direct Oral Anticoagulants vs Warfarin in Older Patients With Atrial Fibrillation and Ischemic Stroke: Findings From the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study

JAMA Neurology

Data from 11,662 patients discharged after stroke shows those on DOACs (v warfarin) had fewer deaths (HR 0.88, P<0.001), all-cause readmissions (0.93; P=0.003), CV readmissions (0.92, P=0.02), haemorrhagic strokes (0.69, P=0.02), and hospitalisation with bleeding (0.89, P=0.009).

 

Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis

British Medical Journal

Review (18 studies;n=7515) found in patients with 1st episode unprovoked VTE who completed ≥3 months anticoagulation, risk of recurrent VTE was 10% in 1st year after treatment, 16% at 2 years, 25% at 5 years, and 36% at 10 years, with 4% of recurrent VTE events resulting in death.

 

 

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

 

Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps: A Randomized Controlled Trial

Annals of Internal Medicine

This RCT (n=184) suggests small colorectal polyps may be resected safely with cold-snare polypectomy while oral anticoagulation continues, compared to heparin bridging with hot-snare polypectomy, and was associated with a lower incidence of major bleeding.

 

Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis

Annals of Internal Medicine

Review of 45 RCTs (n=34,082) concludes in early-stage CKD, non–vitamin K oral anticoagulants (NOACs) had benefit–risk profile superior to that of vitamin K antagonists (VKAs). For advanced CKD or ESKD, there was insufficient evidence to establish benefits or harms of VKAs v NOACs.

 

Rivaroxaban (Xarelto▼): reminder that 15 mg and 20 mg tablets should be taken with food

Medicines and Healthcare products Regulatory Agency

MHRA has received a small number of reports suggesting lack of efficacy (thromboembolic events) in patients taking 15 mg or 20 mg rivaroxaban on an empty stomach. Healthcare professional are advised to remind patients to take 15 mg or 20 mg rivaroxaban tablets with food.

 

Direct Acting Oral Anticoagulants (DOACs) in Renal Impairment: Practice Guide to Dosing Issues

Specialist Pharmacy Service

This paper explains the background to dosing decisions for DOACs in patients with impaired renal function and focusses on the use of DOACs in patients with AF. It provides case study examples from current clinical practice and is intended as a practice aid.

 

 

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

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

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