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

Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial

Annals of Internal Medicine

In this RCT of 190 APS patients, after 3years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76] prespecified noninferiority margin for RR was 1.40).

Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial

The Lancet

RCT of 9202 patients treated within 3hrs of injury reports lower risk of head injury-related death at 28days with tranexamic acid (18.5%) vs placebo (19.8%; RR 0.94 [95% CI 0.86–1.02]), and this was statistically significant in those with mild-moderate injury (RR 0.78, 0.64–0.95).

US FDA approves rivaroxaban (Xarelto) for the prevention of venous thromboembolism in acute medical patients

Biospace Inc.

Approval is based on data from the phase III MAGELLAN and MARINER trials. MAGELLAN met its co-primary endpoints, demonstrating non-inferiority to enoxaparin in short-term (10 days) and superiority in long-term (35 days) use, while MARINER demonstrated reduction in symptomatic VTE.

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: Short-term dual antiplatelet treatment may be best for most patients after receiving a drug-eluting stent

National Institute for Health Research

Expert commentary is provided on a network meta-analysis (17 RCTs, n= 46,864) which showed standard 12-month treatment increased the risk of any bleeding compared with 6 month short-term treatment (OR 1.39, 95% CI 1.01 to 1.92).

Adherence and persistence to direct oral anticoagulants in atrial fibrillation: a population-based study

Heart

Study (n=36,652) found adherence & persistence to direct oral anticoagulants are low at 1 yr with heterogeneity across drugs and over time at individual and system levels. Authors state better understanding of contributory factors will inform interventions to improve adherence.

Antithrombotic treatment after coronary artery bypass graft surgery: systematic review and network meta-analysis

British Medical Journal

Analysis (20 RCTs;n=4083) found moderate evidence to support dual antiplatelet use [aspirin(AS)+ticagrelor; OR 0.50,95% CI 0.31-0.79, NNT 10 or AS+clopidogrel; 0.60;0.42-0.86, 19] to reduce saphenous vein graft failure vs aspirin, with no significant differences in major bleeding.

Comparison of Events Across Bleeding Scales in the ENGAGE AF-TIMI 48 Trial

Circulation

In this study of edoxaban vs warfarin (n=21,105; and 10,311 total bleeding events), there was ~4-fold difference in frequency of most severe bleeding events across commonly used bleeding scales (ISTH, TIMI, GUSTO, and BARC) among patients with AF at risk for stroke.

Long-term Thromboembolic Risk in Patients With Postoperative Atrial Fibrillation After Left-Sided Heart Valve Surgery

JAMA Cardiology

Study found new-onset post op AF (POAF) was linked to a similar long-term risk of thromboembolism as nonvalvular AF (crude incidence rates 21.9 and 17.7 events/1000 person-years respectively), highlighting need for further studies addressing anticoagulation in POAF population.

Revised SPC: Plavix (clopidogrel) tablets

electronic Medicines compendium

SPC now details that co-administration of opioids has the potential to delay and reduce the absorption of clopidogrel due to delayed gastric emptying. The use of parenteral antiplatelet agent in ACS should be considered where opioid co-administration is required.

Direct oral anticoagulant for the prevention of thrombosis in ambulatory patients with cancer: A systematic review and meta-analysis

Journal of Thrombosis and Haemastasis

Review of 28 studies reports that low‐dose direct oral anticoagulant prophylaxis reduces the rate of overall venous thromboembolism in high‐risk cancer patients starting systemic chemotherapy but may increase the risk 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:

http://www.evidence.nhs.uk/about-evidence-services/content-and-sources/medicines-information/new-medicines-awareness-services