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

Antidepressant drug use and subdural hematoma risk

Journal of Thrombosis and Haemastasis

Study (10,885 subdural hematoma (SDH) cases & 435,379 matched controls) found SSRIs (adjusted OR 1.32 [1.25‐1.38]) and non‐SSRIs (aOR 1.19 [1.13‐1.26]) were associated with higher SDH risk vs. non‐use of antidepressants; but absolute risk is judged to be small.

 

Different strategies for pharmacological thromboprophylaxis for lower-limb immobilisation after injury: systematic review and economic evaluation

National Institute for Health Research

Meta-analysis (n=6857; 13 trials) found thromboprophylaxis (TP) in this setting is clinically (low-molecular-weight heparin reduced risk any VTE: OR 0.52, 95% CI, 0.37-0.71) and cost (£13,524 per QALY) effective vs. no TP. Estimates of risk of major bleeding were inconclusive.

 

Hospitalization as an opportunity to correct errors in anticoagulant treatment in patients with atrial fibrillation

British Journal of Clinical Pharmacology

Study (n=4427) found patients with treatment errors (ERs) hospitalised for AF/with stroke history more likely to have such ERs corrected but many ERs are still overlooked. After nontreatment, DOAC underdosing and vitamin K antagonists use instead of DOAC are most common ER types.

 

NHS Scotland approves reimbursement of Hemlibra (emicizumab) for treatment of patient with severe congenital haemophilia A without factor VIII inhibitors

PharmaTimes

In trials, Hemlibra dosed once-weekly or every two weeks led to statistically significant reduction in treated bleeds compared to on-demand treatment. In pooled data a high proportion of patients, both with and without inhibitors, achieved zero treated bleeds.

 

 

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

Improved utilisation of venous thromboembolism prophylaxis in renal-impaired patients following a clinical pharmacist intervention

European Journal of Hospital Pharmacy

Study suggests clinical pharmacist's intervention can improve rate of thrombosis prophylaxis prescription (pre-intervention 34.8% at high VTE risk received pharmacological prophylaxis [PP] vs 100% post intervention (use of PP in low risk VTE patients reduced from 22.2% to 3.3%).

 

Revised SPCs: Plavix (clopidogrel) 75 and 300 mg film-coated tablets

electronic Medicines compendium

SPC now warns that as with other oral P2Y12 inhibitors, co-administration of opioid agonists has potential to delay and reduce absorption of clopidogrel, presumably because of slowed gastric emptying. The clinical relevance is unknown.

 

NIHR Signal: Continuing an anticoagulant at home after abdominal surgery cuts thrombosis risk

NIHR Dissemination Centre

Expert commentary is provided of updated Cochrane review of 7 studies which found 13% patients on anticoagulant treatment only during hospital stay developed thrombosis vs. 5% who continued with treatment beyond discharge, and had no increased risk of bleeding complications.

 

Safety and Efficacy of Intra-arterial Urokinase After Failed, Unsuccessful, or Incomplete Mechanical Thrombectomy in Anterior Circulation Large-Vessel Occlusion Stroke

JAMA Neurology

Cohort study of 993 patients treated with mechanical thrombectomy, including 100 who received additional intra-arterial urokinase showed it was not linked to increased symptomatic intracranial haemorrhage (5.2 v 6.9%) and was associated with better 90-day functional independence.

 

 

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

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

Specialist Pharmacy Service

This updated Medicines Q & A reviews the evidence available and considers when prophylactic doses of low molecular weight heparins can be used in patients with renal impairment.

 

Impact of oral anticoagulation in patients with atrial fibrillation at very low thromboembolic risk

Heart

Study (n=2224) found 44% of low CHA2DS2-VASc patients received oral anticoagulation (OAC). Incidence of non-haemorrhagic stroke/systemic embolism were similar between OAC and not on OAC groups (0.32 vs 0.30 events per 100 person years, respectively; NS; p=0.92).

 

 

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

Ultrasound-accelerated catheter-directed thrombolysis versus anticoagulation for the prevention of post-thrombotic syndrome (CAVA): a single-blind, multicentre, randomised trial

The Lancet Haematology

RCT (184) showed additional ultrasound-accelerated catheter-directed thrombolysis (urokinase) does not change risk of post-thrombotic syndrome 1 year after acute ilio femoral DVT vs. standard therapy (anticoagulation, stockings, early ambulation) [29 vs. 35%; respectively,p=0.42].

 

Venous thromboembolic diseases: diagnosis, management and thrombophilia testing – DRAFT guidance consultation

National Institute for Health and Care Excellence

This DRAFT guideline aims to support quick diagnosis and effective treatment for people who develop DVT or PE. It also covers testing for conditions that can make a DVT or PE more likely, such as thrombophilia (a blood clotting disorder) and cancer.

 

Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation

JAMA Internal Medicine

Study (n=167 275) found that relative to new users of warfarin, new users of DOACs - particularly apixaban – were at lower risk of fractures requiring hospitalisation (hazard ratio for DOAC vs. warfarin 0.87; 95% CI, 0.79-0.96).

 

Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement

Heart

Swedish cohort study (n= 9539) reported that warfarin vs single antiplatelet exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incidence of bleeding events but with similar mortality.

 

 

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

Optimizing heart failure management: anticoagulation, diuretic withdrawal, iron substitution, and novel inotropes

European Heart Journal

Review discusses management options for heart failure with reduced ejection fraction (HfrEF), whether anticoagulation would be protective in patients with ischaemic HfrEF, role of renin–angiotensin system, beta-blockers, mineralocorticoid receptor antagonists and diuretics.

 

Manufacturers report positive data from the TWILIGHT trial for ticagrelor

PharmaTimes

New data from AstraZeneca's TWILIGHT trial has found that Brilinta (ticagrelor) on its own reduced the risk of clinically relevant bleeding compared to dual antiplatelet therapy (DAPT) over 12 months in high-risk patients with non-ST elevation acute coronary syndromes (NSTE-ACS).

 

A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement

New England Journal of Medicine

In 1644 pts without an established indication for oral anticoagulation after transcatheter aortic-valve replacement, treatment with rivaroxaban was associated with a higher risk of death or thromboembolic complications and higher risk of bleeding vs an antiplatelet-based strategy.

 

Anticoagulant Reversal Strategies in the Emergency Department Setting: Recommendations of a Multidisciplinary Expert Panel

Annals of Emergency Medicine

This US-focused anticoagulant reversal and replacement guidance statement is supported by literature and consensus definitions to support evaluation and treatment of the bleeding and nonbleeding patient requiring emergency invasive 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

DTB Commentary: Intensive antiplatelet therapy with three agents does not reduce risk of another stroke

Drug and Therapeutics Bulletin

A commentary on the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) highlights that intensive antiplatelet therapy with three drugs should not be used in routine clinical practice to prevent recurrent events in patients with acute cerebral ischaemia.

 

Association of Testosterone Therapy With Risk of Venous Thromboembolism Among Men With and Without Hypogonadism

JAMA Internal Medicine

Study (n=39,622) found testosterone therapy was associated with an increase in short-term risk for VTE among men with (OR 2.32; 95% CI, 1.97-2.74) and without (2.02; 1.47-2.77) hypogonadism, with some evidence that the association was more pronounced among younger men.

 

Adjunctive Antithrombotic Therapy for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

JAMA Cardiology

Article notes adjunctive antithrombotic therapy used to mitigate thrombotic risks in this population must be balanced against bleeding complications. Evidence for its use remains scarce and no risk prediction models have been established to guide antithrombotic therapy.

 

Actelion withdraws regulatory filings to extend indication of macitentan in chronic thromboembolic pulmonary hypertension

Biospace Inc.

Feedback from regulatory authorities, and from recent study site inspections indicated that additional clinical data would be required for approval. As a result, Actelion has decided to withdraw ongoing worldwide submissions based on phase 2 MERIT-1 study.

 

 

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 compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial

The Lancet Haematology

RCT (n=500) reports fewer symptomatic recurrent venous thromboembolism rates with rivaroxaban: 1% of 335 children receiving weight-adjusted rivaroxaban vs 3% of 165 receiving standard anticoagulants (HR 0.40, 95% CI 0.11–1.41), with similar rates of bleeding in both groups.

 

 

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

Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery The FIBRES Randomized Clinical Trial

Journal of the American Medical Association

RCT of 735 adults who underwent CABG surgery and developed significant bleeding and hypofibrinogenemia post surgery showed similar number of blood components transfused within 24hrs with both fibrinogen concentrate group and cryoprecipitate group (p<0.01 for non-inferiority).

 

Management of Nonvariceal Upper Gastrointestinal Bleeding (UGIB): Guideline Recommendations From the International Consensus Group

Annals of Internal Medicine

Recommendations for patients receiving anticoagulation or antiplatelet therapy have been updated. PPI therapy is recommended to prevent UGIB in patients with previous ulcer bleeding who are receiving single- or dual-antiplatelet or anticoagulant therapy.

 

Prevalence and Knowledge of Potential Interactions Between Over‐the‐Counter Products and Apixaban

Journal of the American Geriatrics Society

Survey (n=791,California) found significant number of patients take OTC meds (particularly dietary supplements) with potentially serious interactions (SIs) with apixaban (33% took ≥1 and 6.7% multiple interacting OTC meds) and they appear to lack knowledge about potentially SIs.

 

Safety and efficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention

European Heart Journal

Review (4 RCTs; n= 10 234) reported lower major or clinically relevant non-major bleeding with double vs. triple antithrombotic therapy (RR 0.66, 95% CI 0.56–0.78; P < 0.0001; I2 = 69%) but at higher risk of stent thrombosis (RR 1.59, 95% CI 1.01–2.50; P = 0.04; I2 = 0%).

 

NIHR Signal: Significant risk of another thrombosis remains if anticoagulation is stopped

NIHR Dissemination Centre

This expert commentary of a meta-analysis (18 studies, n= 7,515) states clinical decisions to cease anticoagulation should remain tailored to each patient's circumstances and balanced against risk of bleeding.

 

Pharmacovigilance Risk Assessment Committee (PRAC) recommends Xeljanz (tofacitinib) be used with caution for all patients at high risk of blood clots

European Medicines Agency

PRAC has concluded that tofacitinib could increase risk of blood clots in the lungs and deep veins in patients who are already at high risk. Also, patients older than 65 years of age should be treated with tofacitinib only when there is no alternative treatment.

 

 

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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