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Venous thromboembolic diseases: diagnosis, management and thrombophilia testing – DRAFT guidance consultation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

Association of General Anesthesia vs Procedural Sedation With Functional Outcome Among Patients With Acute Ischemic Stroke Undergoing Thrombectomy: A Systematic Review and Meta-analysis

Journal of the American Medical Association

Review of 3 RCTs (n=368) found that protocol-based general anaesthesia was associated with less disability at 3 months vs procedural sedation (difference = +0.43 on modified Rankin Scale score, OR 1.58, 95% CI 1.09-2.29).

Compression stockings to prevent post-thrombotic syndrome in adults, a Bayesian meta-analysis

Thrombosis Reasearch

Review of 4 studies found that compression stockings reduced post thrombotic syndrome (PTS) vs. control in acute DVT, but that the difference was not statistically significant (OR = 0.57, 95% CI: 0.21-1.20).

Very Short Dual Antiplatelet Therapy after Drug-eluting Stent Implantation in Patients with High Bleeding Risk: Insight from the STOPDAPT-2 Trial

Circulation

Japanese RCT (n=3,009) found 1-month therapy reduced major bleeding vs. 12-months (0.41% vs. 2.71%, HR 0.15, 95% CI 0.03-0.65, p=0.01); without any increase in CV events (3.48% vs. 5.98%, absolute difference -2.50%, 95% CI -5.06% to 0.06%, HR 0.57, 95% CI 0.32-1.03, p=0.06).

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

Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Asians With Atrial Fibrillation

Stroke

Review, based on subanalyses of 5 RCTs and 21 observational cohorts, found use of NOACs is noninferior vs warfarin with respect to risk of stroke or systemic embolism, all-cause mortality, major bleeding and intracranial bleeding, irrespective of the NOAC type and dose.

Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK

BMJ Open

Database study (n=30 467; 2011-2016) reported 76.9% of patients starting NOACs were prescribed an appropriate dose. Underdosing more frequent in apixaban vs dabigatran and rivaroxaban cohorts. Overdosing more frequent in dabigatran vs rivaroxaban or apixaban cohorts.

Rivaroxaban versus warfarin treatment among morbidly obese patients with venous thromboembolism: Comparative effectiveness, safety, and costs

Thrombosis Reasearch

Retrospective US study of 2890 matched pairs of morbidly obese VTE patients reported similar recurrent VTE risk (OR: 0.99; 95% CI: 0.85–1.14) and major bleeding (0.75: 0.47–1.19) with rivaroxaban vs warfarin. Hospitalizations and outpatient visits were lower with rivaroxaban.

Oral Anticoagulation in patients with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1

European Heart Journal

This report outlines the currently available evidence in this field and provides a risk stratification of the individual thromboembolic risk in patients with AF and a CHA2DS2-VASc score of 1 to guide clinicians on whether to anticoagulate or not.

Revised SPC: Brilique (ticagrelor) film coated tablets – all strengths

electronic Medicines compendium

The SPC has been updated to warn of potential for ticagrelor to interfere with platelet function tests to diagnose heparin induced thrombocytopenia (HIT).

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

Cochrane Database of Systematic Reviews

Updated review of 7 RCTs (n=1728) concludes prolonged thromboprophylaxis (14 days) with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality.

Medical Management vs Mechanical Thrombectomy for Mild Strokes An International Multicenter Study and Systematic Review and Meta-analysis

JAMA Neurology

Pooled analysis of data from 251 patients with mild-deficit emergency large-vessel occlusion stroke concludes mechanical thrombectomy has a similar efficacy and safety profile vs best medical management, and a separate systematic review confirms this finding.

Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or with Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights from the AUGUSTUS Trial

Circulation

Study (n=4,614) shows regimen of apixaban + P2Y12 inhibitor without aspirin provides superior safety & similar efficacy in atrial fibrillation patients who have ACS (managed medically or with PCI), or those undergoing elective PCI; vs. regimens with VKAs, aspirin, or both.

Female sex as a risk factor for ischaemic stroke varies with age in patients with atrial fibrillation

Heart

Study (n=159,222) found the female/male ischaemic stroke risk ratio varied with age. Only women aged >75 years had a higher risk, whereas women aged <65 years had a lower risk vs. men. Authors state findings challenge the 'sex category' of the CHA2DS2-VASc score.

Ticagrelor with or without Aspirin in High-Risk Patients after PCI

New England Journal of Medicine

RCT (n=7,119) found ticagrelor monotherapy was associated with lower incidence of clinically relevant bleeding vs. ticagrelor + aspirin (1.0% vs. 2.0%; HR 0.49; 95% CI, 0.33 to 0.74), with no higher risk of death, myocardial infarction, or 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