Revised SPCs: Pradaxa (dabigatran) 150mg, 110mg and 75mg hard capsules

Electronic Medicines Compendium
The SPCs have been extensively revised following addition of a new indication for use of dabigatran in the treatment of DVT and PE and prevention of recurrent DVT and PE in adults. Wording for the interaction with verapamil has been strengthened in view of bleeding risk.


Long-Acting clotting Factor VIIa-CTP receives positive opinion for three orphan drug designations in Europe

Biospace Inc.
This positive opinion recommends approval of orphan drug designation for long-acting version of clotting Factor VIIa (IV or SC route) for treatment of bleeding episodes in patients with haemophilia A or B with inhibitors to Factor VIII or IX and congenital Factor VII deficiency.


Antipsychotic drugs and risks of myocardial infarction: a self-controlled case series study

European Heart Journal
This study suggests an increased MI risk during the 30 days after first prescription of an antipsychotic. Although the small absolute risk is unlikely to alter risk/benefit balance in licensed conditions, it is likely to be less favourable for unlicensed uses (e.g. dementia).


Quadrivalent Human Papillomavirus Vaccine and the Risk of Venous Thromboembolism

Journal of the American Medical Association
This self-controlled case-series found no evidence for an increased risk of venous thromboembolism during the 42 days after quadrivalent HPV vaccination. The lack of association was apparent in subgroup analyses according to age, and after adjustment for oral contraceptive use.


Low molecular weight heparin versus unfractionated heparin for perioperative thromboprophylaxis in patients with cancer

Cochrane Database of Systematic Reviews
No evidence was found between perioperative thromboprophylaxis with LMWH versus UFH in their effects on mortality, thromboembolic outcomes, major or minor bleeding in patients with cancer. Further trials are needed to evaluate different heparin thromboprophylaxis strategies.


Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial

The Lancet
This pragmatic study in patients undergoing primary PCI found that the incidence of major cardiac adverse events (MACE) at 28 days was lower with heparin than with bivalirudin (5.7% vs. 8.7%, respectively; p=0.01), with no difference between groups in bleeding complications.



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Anticoagulation therapy versus placebo for pulmonary hypertension

Cochrane Database of Systematic Reviews
No randomised evidence is available. The results of other studies (non-RCTs) provide only poor quality evidence of effectiveness of this intervention, and the results should be interpreted with caution. This review therefore highlights need for appropriately designed RCTs.


Desmoteplase fails to meet primary endpoint in Phase III study of acute ischaemic stroke

Biospace Inc.

The first of two Phase III studies of desmoteplase in the treatment of acute stroke within 3-9 hours after onset (DIAS-3) has failed to meet its primary endpoint (proportion of patients with a favourable outcome at day 90 compared to placebo; 51.3% v 49.8%, respectively).


European CHMP recommends approval of apixaban for treatment of DVT and PE and prevention of recurrence

European Medicines Agency

The CHMP has recommended a license extension for apixaban (Eliquis®) to include its use for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of recurrent DVT and PE in adults.


Point-of-Care Testing of International Normalized Ratio for Patients on Oral Anticoagulant Therapy: Systematic Review and Economic Analysis

Canadian Agency for Drugs and Technologies in Health
Point of care (POC) INR technologies were found to be generally precise and accurate when INR values are in commonly targeted therapeutic range. There was no significant difference in risk of hemorrhagic/thromboembolic events between POC and standard laboratory testing methods.


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

The Lancet
RCT (n=1228) found preconception-initiated low-dose aspirin not significantly linked to livebirth or pregnancy loss (PL) in women with 1/2 previous losses vs. placebo, and is thus not recommended for prevention of PL. Increased vaginal bleeding with aspirin was not linked to PL.


CMC Biologics announces development plans for first-in-class factor Xa inhibitor antidote Andexanet Alfa

Biospace Inc.
CMC Biologics, Inc. has entered in to a commercial supply agreement with Portola Pharmaceuticals, for the development of andexanet alfa, a potential first-in class factor Xa inhibitor antidote, for use in patients with a major bleed/who require emergency surgery.


Supporting local implementation of NICE guidance on use of the non Vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation

National Institute for Health and Care Excellence
This consensus report was developed following a workshop meeting discussing barriers to use of non-Vitamin K antagonist oral anticoagulants for reducing stroke risk in non-valvular AF and how these barriers might be overcome locally to facilitate appropriate use of the drugs.



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:

Prophylaxis against Venous Thromboembolism in Ambulatory Patients with Cancer

New England Journal of Medicine
This article outlines the risks and rates of VTE from trial data, discusses US guidance which overall does not endorse routine prophylaxis, and concludes that further studies on morbidity, mortality, and cost for this patient population are required.


NICE issues Final Appraisal Determination on prasugrel with PCI for treating ACS

National Institute for Health and Care Excellence
NICE has issued DRAFT guidance (FAD) recommending the use of prasugrel 10mg in combination with aspirin as an option for preventing atherothrombotic events in adults with acute coronary syndrome having primary or delayed percutaneous coronary intervention.


Boehringer Ingelheim announces new study to evaluate dabigatran for patients with AF undergoing ablation

Biospace Inc.
A new study (RE-CIRCUIT™) will investigate the safety and efficacy of uninterrupted anticoagulant treatment with dabigatran (Pradaxa®) in patients with atrial fibrillation who undergo ablation. Results of the study are expected in 2016.



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:



Atrial fibrillation (update) (CG180)

National Institute for Health and Care Excellence
New recommendations in this updated guideline include a personalised package of care and information, referral for specialised management, stroke prevention, rate and rhythm control and the management of acute atrial fibrillation.


Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage: A Meta-analysis

Journal of the American Medical Association
Thrombolysis is associated with lower mortality (2.17% vs 3.89%; NNT 59) and recurrent PE (1.17% vs 3.04%; NNT 54) but higher risk of major bleeding (9.24% vs 3.42%; NNH 18) and intracranial haemorrhage (1.46% vs 0.19%; NNH 78), compared with anticoagulation in patients with PE.


Genotype-Guided vs Clinical Dosing of Warfarin and Its Analogues: Meta-analysis of Randomized Clinical Trials

JAMA Internal Medicine
This meta-analysis of 9 randomised studies (n=2,812) found that genotype-guided warfarin dosing was no better than clinical dosing protocols in terms of time within INR therapeutic range, number of patients with an INR>4, or incidence of major bleeding or thromboembolic events.


Vitamin K for improved anticoagulation control in patients receiving warfarin

Cochrane Database of Systematic Reviews
Two studies compared whether low dose (150 to 175 mcg) vitamin K given to patients with a high-variability response to warfarin improved INR control. One study showed significant improvement, while another smaller study suggested no overall benefit.


Phase III data for eltrombopag in paediatric patients with chronic immune thrombocytopenia

Biospace Inc.
In a Phase III study of paediatric patients with previously treated chronic immune (idiopathic) thrombocytopenic purpura (PETIT2; n=93), a consistent platelet response for 6 of 8 weeks was achieved in 39.7% of patients treated with eltrombopag (vs. 3.4% with placebo; p<0.001).



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:




Reducing Postoperative Venous Thromboembolism Complications with a Standardized Risk-Stratified Prophylaxis Protocol and Mobilization Program

Journal of the American College of Surgeons
A patient care program focusing on early postoperative mobilisation, mandatory VTE risk stratification and electronic prophylaxis recommendations, significantly reduced likelihood of VTE complications from 1.9% to 0.3% (p < 0.01) and PE from 1.1% to 0.5% (p < 0.01).


Revised SPC: Nuvaring (ethinylestradiol/etonogestrel)

electronic Medicines Compendium
Further information on risk of venous thromboembolism has been added to a number of sections. Section 4.8 now lists arterial thromboembolism (rare) and chloasma (incidence unknown) as potential side-effects.


FDA approves Eloctate™ (antihaemophilic Factor (recombinant), Fc Fusion Protein) for haemophilia A

Biospace Inc.
The US FDA has approved Eloctate™ [Antihaemophilic Factor (Recombinant), Fc Fusion Protein] for the control and prevention of bleeding episodes, perioperative management and routine prophylaxis in adults and children with haemophilia A.



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:

Time to treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice: retrospective analysis of hospital quality assurance data with comparison with results from randomised clinical trials

British Medical Journal
In this study (n=84,439), the effectiveness of thrombolytic therapy in clinical practice was comparable with that shown in clinical trials, with a clear association between time to treatment and functional outcome. Therapy >4.5 hrs was associated with an increase in mortality.


Chronic thromboembolic pulmonary hypertension

The Lancet Respiratory Medicine
This review looks at the diagnosis and treatment of chronic thromboembolic pulmonary hypertension, a debilitating and life-threatening complication of acute pulmonary embolism that results from persistent obstruction of pulmonary arteries and progressive vascular remodelling.



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:

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

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

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:



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

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:

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:


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: