Delay in Filling First Clopidogrel Prescription After Coronary Stenting Is Associated With an Increased Risk of Death and Myocardial Infarction

Journal of the American Heart Association
Study of 15 629 patients treated with coronary stents found delay >3 days in obtaining 1st script for clopidogrel is predictive of mortality and recurrent MI (DES: HR, 2.4; 95% CI, 1.7 to 3.4; and 2.0; 1.5 to 2.7, and BMS: 2.2; 1.9 to 2.6; and 1.8; 1.5 to 2.1, respectively).

 

Boehringer to settle lawsuits against dabigatran (Pradaxa) in US

Reuters
Boehringer Ingelheim is to pay about $650 million to settle U.S. lawsuits that claimed dabigatran had caused severe and fatal bleeding in patients. The claimants had accused the company of not issuing sufficient warnings of the risks associated with this drug.

 

Vitamin K Antagonists and Risk of Subdural Hematoma: Meta-Analysis of Randomized Clinical Trials

Stroke
This meta-analysis (19 RCTs; n=92,156) found the risk of subdural haematoma associated with vitamin K antagonists to be higher than the risk with antiplatelets (odds ratio 3.0; 95% CI 1.5–6.1), factor Xa inhibitors (2.9; 2.1–4.1) and direct thrombin inhibitors (1.8; 1.2–2.7).

 

 

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

 

 

Bivalirudin is superior to heparins alone with bailout GP IIb/IIIa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a pre-specified analysis from EUROMAX trial

European Heart Journal
Analysis (n=2198) found death and major bleeding occurred in 5.1% on bivalirudin, 7.6% on heparin plus routine GPI (HR 0.67; 95% CI 0.46–0.97, p=0.034), and 9.8% on heparins plus bailout GPI (0.52; 0.35–0.75, p=0.006). Rates of stent thrombosis were higher with bivalirudin.

 

Posterior circulation ischaemic stroke

British Medical Journal
This review aims to demonstrate the importance and challenges of recognising and treating posterior circulation stroke, which accounts for 20-25% of ischaemic strokes. It discusses causes, clinical symptoms and signs, and its diagnosis and management.

 

Management of Anticoagulation Around Pacemaker and Defibrillator Surgery

Circulation
This Clinician Update discusses the management of warfarin and the new oral anticoagulants (NOACs) around the time of surgery in patients having defibrillator and pacemaker surgery, illustrated with two case examples, for which recommendations on suggested management are given.

 

European Medicines Agency recommends approval of simoctogog alfa (Nuwiq®) for treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency)

European Medicines Agency
The European CHMP has recommended approval of simoctogog alfa (Nuwiq) for the treatment and prophylaxis of bleeding in paediatric and adult patients with haemophilia A (congenital factor VIII deficiency).

 

 

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

Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial

The Lancet Neurology
No benefit was seen in the use of simvastatin (40mg daily for upto 21 days) for long-term or short-term outcome in patients with aneurysmal subarachnoid haemorrhage (n=803). It is concluded these patients should not be treated routinely with simvastatin during acute stages.

 

Is there more to learn about cytochrome P450 enzymes?

Drug and Therapeutics Bulletin
This article provides a brief overview of cytochrome P450 (CYP) enzyme classification, drug interactions, P-glycoprotein and CYP3A4, pharmacogenomics and CYP P450; and alteration of CYP P450 activity by disease.

 

Pradaxa (dabigatran): Drug Safety Communication - Lower Risk for Stroke and Death, but Higher Risk for GI Bleeding Compared to Warfarin

US Food and Drug Administration
Results of an observational cohort study carried out by the FDA as part of its ongoing review of dabigatran have shown it to be associated with a lower risk of ischaemic stroke, ICH and death, and increased risk of major GI bleeding and a similar risk of MI compared to warfarin.

 

Revised SPC: Eliquis (apixaban) 2.5mg and 5mg film-coated tablets

electronic Medicines Compendium
A statement that patients can stay on apixaban while being cardioverted has been added to section 4.2 (Posology and method of administration).

 

 

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

 

Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction

European Heart Journal
This RCT (n=548 of 1240 planned patients) was unable to demonstrate significant differences in net clinical outcome between prasugrel + bivalirudin and clopidogrel + heparin at 30 days, though results must be interpreted with caution in view of premature termination of trial.

 

Antithrombotic treatment in patients with heart failure and associated atrial fibrillation and vascular disease: A nationwide cohort study

Journal of the American College of Cardiology
Study (n=37,464) found that in AF patients with co-existing HF and vascular disease, adding single antiplatelet on top of VKA therapy is not associated with additional benefit on thromboembolic or coronary risk, but notably increased bleeding risk (HR 1.31; 95% 1.09-1.57).

 

Edoxaban: a focused review of its clinical pharmacology

European Heart Journal
The review discusses effects on coagulation parameters and on bleeding in animal models, use of combination therapy in animal models, pharmacokinetics and link to bleeding, pharmacodynamics, metabolism, drug/food interactions; and reversal of anticoagulant effects.

 

Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-leg immobilization

Cochrane Database of Systematic Reviews
Review of 6 RCTs (n=1490) found use of LMWH in outpatients significantly reduces VTE when immobilisation of lower leg is required (OR 0.49; 95% CI, 0.34-0.72). Complications of major bleeding were extremely rare (0.3%) and there were no reports of heparin-induced thrombocytopenia.

 

FDA requests further information for investigational antiplatelet agent cangrelor

Biospace Inc.
The US FDA has issued a Complete Response Letter for the investigational intravenous antiplatelet agent cangrelor requesting further information for the PCI and BRIDGE indications. Cangrelor is also being reviewed by the European Medicines Agency.

 

 

 

 

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

Anticoagulant treatment for subsegmental pulmonary embolism

Cochrane Database of Systematic Reviews
There were no RCT evidence for the effectiveness and safety of anticoagulation therapy versus no intervention in patients with isolated or incidental subsegmental pulmonary embolism and therefore no conclusions can be drawn.

 

Perioperative management of patients on new oral anticoagulants

British Journal of Surgery
This review discusses monitoring of new oral anticoagulants, comparison with warfarin, discontinuation before and restarting after surgery, management of bleeding complications, and use for thromboprophylaxis after orthopaedic surgery.

 

Platelet transfusion infection: risk review

Department of Health
This report details the reasons why the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) does not currently recommend the introduction of pathogen inactivation of platelets for UK blood services.

 

European Medicines Agency recommends extension of dabigatran indications to include treatment of DVT and PE and prevention of recurrence

European Medicines Agency
The European CMHP has recommended the approval of dabigatran etexilate (Pradaxa®) for a new indication - the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.

 

 

 

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

 

Periprocedural Stroke and Bleeding Complications in Patients undergoing Catheter Ablation of Atrial Fibrillation with Different Anticoagulation Management: Results from the "COMPARE" Randomized Trial

Circulation
This open-label study (n=1584) found that performing catheter ablation for AF without stopping warfarin reduced the incidence of thromboembolic events 48 hours post-ablation, when compared to stopping warfarin and bridging with LMWH (0.25% v 4.9%, respectively; p<0.001).

 

Door-to-Needle Times for Tissue Plasminogen Activator Administration and Clinical Outcomes in Acute Ischemic Stroke Before and After a Quality Improvement Initiative

Journal of the American Medical Association
This US study found implementation of a national quality improvement initiative for acute ischaemic stroke improved door-to-needle times for tPA administration; this was associated with lower in-hospital mortality (9.93% v 8.25%) and ICH (5.68% v 4.68%; both P<0.001).

 

Effect of the Use of Ambulance-Based Thrombolysis on Time to Thrombolysis in Acute Ischemic Stroke: A Randomized Clinical Trial

Journal of the American Medical Association
Use of a specialised ambulance in which patients could have thrombolysis administered before transport to hospital where appropriate decreased time to treatment by 25 min, with no increase in adverse events. Further studies are needed to assess effects on clinical outcomes.

 

Thrombocytosis is associated with increased short and long term mortality after exacerbation of chronic obstructive pulmonary disease: a role for antiplatelet therapy?

Thorax
Thrombocytosis was associated with 1-year mortality (OR 1.53 (95% CI 1.03 to 2.29, p=0.030) but treatment with an antiplatelet drug (aspirin or clopidogrel) reduced this mortality rate (OR 0.63 (95% CI 0.47 to 0.85, p=0.003) in 1343 patients with acute exacerbations of COPD.

 

Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery

European Heart Journal
This review specifically addresses; risk stratification for bleeding and recurrent ischaemic events, temporary interruption of antiplatelet therapy, bridging strategies, use of platelet function monitoring, and blood sparing management 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

Antiplatelet Therapy for Stable Coronary Artery Disease in Atrial Fibrillation Patients Taking an Oral Anticoagulant: A Nationwide Cohort Study

Circulation
This study in 8700 AF pts with stable CHD found addition of antiplatelet to vitamin K antagonist not linked to reduced risk of recurrent coronary events/thromboembolism, whereas bleeding risk increased significantly: HR aspirin 1.50; 95% CI, 1.23–1.82; clopidogrel 1.84; 1.11–3.06

 

Venous thromboembolic diseases: Evidence Update April 2014

National Institute for Health and Care Excellence 
A summary of selected new evidence published since the NICE guidance on venous thromboembolic diseases (CG 144; 2012) notes that rivaroxaban, apixaban, dabigatran and edoxaban have since been approved and have been or are currently being reviewed by NICE.

 

Bleeding Risk of Patients With Acute Venous Thromboembolism Taking Nonsteroidal Anti-Inflammatory Drugs or Aspirin

JAMA Internal Medicine
This analysis of observational data from the EINSTEIN clinical trials (n=8246) found that use of aspirin or NSAIDs concomitantly with anticoagulation increased the risk of clinically relevant or major bleeding in patients with venous thromboembolism.

 

Anticoagulation in atrial fibrillation

British Medical Journal
This review discusses the rationale for anticoagulation in patients with atrial fibrillation; risk stratification for treatment; available agents; the appropriate implementation of these agents; and additional, specific clinical considerations for treatment.

 

Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism

New England Journal of Medicine
This study (n=1,006) of normotensive patients with intermediate-risk PE found that use of tenecteplase reduced the risk of death or haemodynamic decompensation (2.6% v 5.6% heparin alone) but increased the risk of major bleeding (11.5% v 2.4%) and stroke (2.4% v 0.2%).

 

 

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-Dose Aspirin for Prevention of Morbidity and Mortality From Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Services Task Force

Annals of Internal Medicine

This review found low-dose aspirin was associated with absolute risk reductions of 2-5% for preeclampsia (RR 0.76; 95% CI 0.62 to 0.95), 1-5% for intrauterine growth restriction (0.80; 0.65 to 0.99), and 2-4% for preterm birth (0.86; 0.76 to 0.98), depending on baseline risk.

 

Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in people with non-valvular atrial fibrillation

Cochrane Database of Systematic Reviews
DTIs found to be as efficacious as VKAs for composite outcome of vascular death and ischaemic events; only dabigatran dose 150mg BD found superior to warfarin. DTIs linked to fewer major haemorrhagic events. ADRs leading to treatment discontinuation occurred more often with DTIs.

 

FDA approves dabigatran (Pradaxa®) for treatment and reduction in the risk of recurrent deep vein thrombosis and pulmonary embolism

Biospace Inc.
The US FDA has approved dabigatran etexilate mesylate (Pradaxa®) for the treatment of DVT and PE in patients who have been treated with a parenteral anticoagulant for 5-10 days, and to reduce the risk of recurrent DVT and PE in patients who have been previously treated.

 

Low molecular weight heparin for prevention of central venous catheterization-related thrombosis in children

Cochrane Database of Systematic Reviews
A single study reported imprecise effects for the risk of CVC-related thrombosis in children on a CVC anticoagulant prophylaxis regimen. The quality of the evidence was low due to the fact that the included study was clearly underpowered, hampering any conclusions.

 

Balancing stroke and bleeding risks in patients with atrial fibrillation and renal failure: the Swedish Atrial Fibrillation Cohort study

European Heart Journal
This Swedish registry based study (n=307,351) concluded that patients with both AF and renal failure will benefit most from having the same treatment as recommended for other patients with AF, without setting a higher or lower threshold for treatment.

 

New SPCs: Voncento (factor VIII, von willebrand factor) 500 IU / 1200 IU and 1000 IU / 2400 IU powder and solvent for solution for injection/infusion

electronic Medicines Compendium
Two SPCs are now available for a new product - Voncento® (factor VIII, von willebrand factor).

 

Point-of-care coagulometers (the CoaguChek XS system and the INRatio2 PT/INR monitor): diagnostics consultation

National Institute for Health and Care Excellence
DRAFT NICE guidance recommends the CoaguChek XS system for self-monitoring coagulation status in people on long-term vitamin K antagonist therapy who have AF or heart valve disease if certain caveats are met. The INRatio2 PT/INR monitor is only recommended for use in research.

 

 

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

 

Recent Advances in Antidotes for Direct Oral Anticoagulants: Their Arrival Is Imminent

Canadian Journal of Cardiology

Several antidotes for direct oral anticoagulants are being developed and recently presented data have raised hopes that their introduction into clinical practice is imminent. In this article, the authors review the latest advances in their development.

 

FDA approves first long-acting recombinant coagulation Factor IX concentrate (Alprolix) for patients with haemophilia B

Biospace Inc.

This has been approved in US for control and prevention of bleeding episodes, perioperative management and routine prophylaxis, in patients with haemophilia B. It was developed using Fc fusion and thus has a more prolonged circulation in body which extends time between infusions.

 

Lack of Concordance between Empirical Scores and Physician Assessments of Stroke and Bleeding Risk in Atrial Fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry

Circulation

This analysis of 10,094 AF patients found little agreement between provider-assessed risk and empirical stroke and bleeding risk scores in AF. These differences may partly explain current divergence of anticoagulation treatment decisions from guideline recommendations.

 

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation

Circulation

These US guidelines for management of atrial fibrillation cover: • Pathophysiology • Clinical evaluation: • Prevention of thromboembolism • Rate control • Rhythm control • Specific patient groups • Evidence gaps and future research directions

 

Combined oral contraceptives: venous thrombosis

Cochrane Database of Systematic Reviews

All COCs investigated in this analysis were linked to increased risk of VTE. The effect size depended both on progestogen used and dose of ethinylestradiol (EE). Thus COCs with lowest possible dose of EE and good compliance should be prescribed, i.e. 30 μg EE with levonorgestrel.

 

Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial

The Lancet

In women with 1 or 2 losses, there was no difference in live birth rate (309/535 for aspirin vs 286/543 for placebo; p=0•0984). However, in women with 1 loss at less than 20 weeks gestation, there was a significant difference (151/242 for aspirin vs 133/250 for placebo; p=0•0446)

 

Vibropulse for cellulitis or venous leg ulcers

Midlands Medicines

This is an evidence based summary of Vibropulse™, a device that utilises cycloidal vibration therapy and is prescribable on an FP10 for cellulitis or venous leg ulcers. The review concludes that there are currently insufficient data in this area to recommend its use.

 

 

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

 

 

 

 

 

 

 

Five-Year Survival in Patients with ST-Segment Elevation Myocardial Infarction According to Modalities of Reperfusion Therapy: The French Registry on Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) 2005 Cohort

 

Circulation

 

This analysis of registry data reports 5-year survival following STEMI of 88% for patients receiving fibrinolysis, 83% for PCI and 59% for no reperfusion. The authors suggest a pharmaco-invasive strategy constitutes a valid alternative to PCI on a nationwide scale.

 

 

Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial

 

European Heart Journal

 

This analysis of data from 779 pts experiencing major bleeding during ROCKET AF found administration of fresh frozen plasma and prothrombin complex concentrates was less frequent in the rivaroxaban arm. Use of transfused packed RBC and outcomes were however similar to warfarin.

 

 

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