Items filtered by date: May 2018

Periprocedural Outcomes of Direct Oral Anticoagulants vs. Warfarin in Non-Valvular Atrial Fibrillation: A Meta-analysis of Phase III Trials

Circulation

Meta-analysis of sub-analysis of RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF trials found in short-term, safety/efficacy of DOACs and warfarin (WF) periprocedurally are not different. DOACs were linked to 38% lower risk of major bleeding vs. WF with uninterrupted anticoagulation.

 

Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation

Cochrane Database of Systematic Reviews

Review of 13 RCTs (n=67,688), most of which involved apixaban, edoxaban, rivaroxaban, found treatment with factor Xa inhibitors significantly reduced number of strokes and systemic embolic events vs. warfarin with AF; the absolute effect vs. warfarin was, however, rather small.

 

US FDA accepts supplemental biologics license application for prophylactic and paediatric use of Coagadex® (Coagulation Factor X, Human) for treatment of hereditary factor X deficiency

Biospace Inc.

Application relates to use in children under 12 years of age and is based on data from phase 3 prospective TEN02 study in children with moderate to severe deficiency. Coagadex is currently only licensed in UK for use in children over age of 12 years.

 

Data from Haven III and Haven IV trials suggest efficacy of emicizumab in haemophilia patients without factor VIII inhibitors

PharmaTimes

A 96% and 97% reduction in treated bleed were found in these studies respectively vs no prophylaxis. Emicizumab is currently licensed for routine prophylaxis of bleeding episodes in patients with haemophilia A with factor VIII inhibitors.

 

US FDA approves avatrombopag (Doptelet) for treatment of thrombocytopenia in patients with chronic liver scheduled to undergo a medical or dental procedure

Biospace Inc.

This thrombopoietin receptor agonist has been evaluated in ADAPT-1 /ADAPT-2 trials (n=435) which reported higher proportion of patients had increased platelet (PL) counts and did not require PL transfusion/rescue therapy on day of -and up to 7 days after procedure vs. placebo.

 

Use of Venous Thromboembolism Prophylaxis in Hospitalized Patients

JAMA Internal Medicine

Analysis (n=44,775 in 52 Michigan hospitals) noted anticoagulant (AC) use among low-risk patients (18 584 [57.1%]) was most important contributor to excess use of VTE prophylaxis. Excess use of mechanical VTE prophylaxis was common among both low-and high risk patients.

 

Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Frail Patients With Nonvalvular Atrial Fibrillation

Journal of the American Heart Association

At 2 yrs, database study (n=19077) found no difference in stroke or systemic embolism (SE) with apixaban or dabigatran (HR=0.78 % 0.94) or major bleeding (0.72 & 0.87) vs warfarin. Rivaroxaban reduced stroke or SE (0.68) without altering major bleeding risk (1.07) vs warfarin.

 

Revised SPC: Brilique (ticagrelor) – all formulations

electronic Medicines compendium

SPC now states that delayed and decreased exposure to oral P2Y12 inhibitors, including ticagrelor (TG) and active metabolite, has been observed in patients with ACS on morphine (35% reduction in TG exposure). May apply to other opioids; clinical relevance unknown.

 

 

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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New product: Exembol (argatroban) 1 mg/mL Solution for Infusion - Ready to Use

electronic Medicines compendium

This is a new additional presentation of argatroban (other formulation is multidose 100 mg/ml concentrate that needs to be diluted), which is licensed for anticoagulation in adult patients with heparin-induced thrombocytopenia type II who require parenteral antithrombotic therapy.

 

Pharmacogenomic Approach to Selecting Antiplatelet Therapy in Patients With Acute Coronary Syndromes: The PHARMCLO Trial

Journal of the American College of Cardiology

Study (n=888) which was prematurely stopped, suggests personalised approach to selecting antiplatelet may reduce ischaemic and bleeding events [primary endpoint occurred in 71 (15.9%) in pharmacogenomic and 114 (25.9%) in standard-of-care arm; HR 0.58;95% CI; 0.43-0.78;p <0.001].

 

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study

The Lancet Neurology

Study (n=1447) found that in patients with AF anticoagulated after recent ischaemic stroke /TIA, cerebral microbleed presence is linked to symptomatic intracranial haemorrhage risk (HR 3.67,95% CI 1.27–10.60 vs.absence microbleeds) and could help inform anticoagulation decisions.

 

Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial

The Lancet Neurology

RCT (n=1534 from 3 Asian countries) reported cilostazol was non-inferior to aspirin for the prevention of cardiovascular events (HR 0.80, 95% CI 0.57–1.11; non-inferiority p=0.0077); but did not reduce the risk of haemorrhagic stroke(HR 0.51, 97.5% CI 0.20–1.27).

 

Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA

New England Journal of Medicine

RCT (n=4,881) found that clopidogrel plus aspirin was associated with a lower risk of major ischaemic events vs aspirin alone at 90 days (5% vs 6.5%, HR 0.75, p=0.02) but an increased risk of major haemorrhage (0.9% vs 0.4%, 2.32, p=0.02).

 

MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset

New England Journal of Medicine

RCT was stopped early owing to cessation of funding (n=503 from 800 anticipated). Favourable outcome (score of 0 or 1 on the modified Rankin scale of neurologic disability) was reported in 53.3% given altepase vs 41.8% for placebo (adjusted OR 1.61, p=0.02).

 

Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source

New England Journal of Medicine

RCT (n=7,213) was terminated early due to lack of benefit in stroke risk and worse bleeding outcomes for rivaroxaban vs aspirin (annualised major bleeding with rivaroxaban was 1.8% vs 0.7% for aspirin, HR 2.72, p<0.001).

 

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial

The Lancet

RCT (n=2.325) found no difference in functional status at day 90 (primary outcome) for tranexamic acid vs placebo (adjusted OR 0.88, 95% CI 0.76 to 1.03), although there were fewer deaths by day 7 with tranexamic acid (9% vs 11% 0.73, 0.53 to 0.99).

 

Management of Bleeding in Patients Taking Oral Anticoagulants

Journal of the American Medical Association

This US decision pathway from the American College of Cardiology details management of patients who experience either life-threatening bleeding or major bleeding at a critical site. Ceasing the anticoagulant, supportive measures and reversal agents are the major strategies.

 

 

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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Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D)

Journal of Clinical Oncology

RCT (n=203) found that rivaroxaban was associated with relatively low venous thromboembolism VTE recurrence vs dalteparin (6 month recurrence rate 11% vs 4%; HR 0.43; 95% CI, 0.19 to 0.99). Corresponding 6 months rates of clinically relevant non-major bleeding were 4% vs 13%.

 

Appropriateness of oral anticoagulant therapy prescription and its associated factors in hospitalized older people with atrial fibrillation

British Journal of Clinical Pharmacology

Of 328 Italian patients, 143 were inappropriately prescribed with oral anticoagulants (OACs), 88 of which were under prescribed or prescribed with an inappropriate drug. Among 55 of 221 patients prescribed OACs, dosing errors were the most frequent cause of inappropriate use.

 

Hospital admissions for bleeding events associated with treatment with apixaban, dabigatran and rivaroxaban

European Journal of Hospital Pharmacy

This retrospective observational study identified 37 hospitalisation episodes for DOAC-induced bleeding in 32 patients (15 rivaroxaban, 9 apixaban and 8 dabigatran; incidence rate 3.44 [95% CI 2.35 to 4.86] per 100 person-years), most commonly gastrointestinal (27 cases, 73.0%).

 

Stability of repackaged dabigatran etexilate capsules in dose administration aids

European Journal of Hospital Pharmacy

Repackaged capsules stored in the refrigerator for 28 days had a drug content of 98.2% and dissolution was not significantly affected (p=0.132). If repackaging of Pradaxa capsules is required, storage under refrigerated conditions ensures quality for 28 days.

 

Periprocedural management of patients receiving novel oral anticoagulants

European Journal of Hospital Pharmacy

This review of guidelines and evidence for the use of non-vitamin K oral antagonists highlights discrepancies between US and European guidelines. However, consensus about postoperative resumption is clear: 24 and 48–72hours, after low- and high-risk bleeding surgery, respectively.

 

 

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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Calciphylaxis

New England Journal of Medicine

Calciphylaxis is a life-threatening syndrome of vascular calcification characterised by occlusion of microvessels in the subcutaneous adipose tissue and dermis. This review presents current understanding of the condition and provides a framework for interdisciplinary management.

 

Antifibrinolytic drugs for treating primary postpartum haemorrhage

Cochrane Database of Systematic Reviews

Review of data from 3 RCTs (n=20,412) concludes tranexamic acid, when administered intravenously, reduces mortality due to bleeding in women with primary postpartum haemorrhage, irrespective of mode of birth, and without increasing the risk of thromboembolic events.

 

Treatment for superficial thrombophlebitis of the leg

Cochrane Database of Systematic Reviews

Review of 33 RCTs (n=7296) concludes prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for superficial thrombophlebitis of the legs for most people. Evidence on topical treatment/surgery is too limited and cannot inform clinical practice.

 

Fostamatinib for the Treatment of Adult Persistent and Chronic Immune Thrombocytopenia: Results of Two Phase 3, Randomized, Placebo-Controlled Trials

American Journal of Hematology

Results from these RCTs (n=150) show that stable responses (defined as platelets ≥50,000/μL at ≥4 of 6 biweekly visits) occurred in 18% of patients on fostamatinib vs. 2% on placebo (P=0.0003). Median time to response was 15 days (on 100mg bd).

 

Genotype‐guided warfarin dosing versus conventional dosing strategies: a systematic review and meta‐analysis of randomized controlled trials

British Journal of Clinical Pharmacology

Genotype‐guided dosing (GGD; n=5230) reduced time‐to‐first therapeutic INR (mean 2.6 days; P<0.0001; I2 0%) and time‐to‐first stable INR (5.9 days; P<0.01; I2 94%) vs conventional dosing. GGD also increased time in therapeutic range and reduced risks of INR ≥ 4 and 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

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