Effect of Warfarin Treatment on Survival of Patients with Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL)

Circulation

Trial (n=187 on warfarin and 187 matched controls) found no significant survival advantage was observed in patients on warfarin. In patients with PAH linked to systemic sclerosis, long-term warfarin was associated with poorer survival than in patients not on warfarin.

Clinical outcomes in patients with ST-segment elevation myocardial infarction treated with everolimus-eluting stents versus bare-metal stents (EXAMINATION): 5-year results of a randomised trial

The Lancet

RCT (n=1498) found patient-oriented endpoint occurred in 159 (21%) patients in the everolimus-eluting stents group vs. 192 (26%) in the bare-metal stents group (HR 0.80, 95% CI 0.65–0.98; p=0.033). This difference was mainly driven by a reduced rate of all-cause mortality.

Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and a history of cryptogenic stroke or transient ischemic attack

Cochrane Database of Systematic Reviews

The combined data from recent RCTs have shown no statistically significant differences between these interventions in prevention of recurrent ischaemic stroke.

Treatment and Outcome of Thrombolysis-Related Hemorrhage: A Multicenter Retrospective Study

JAMA Neurology

This US study of 128 patients with symptomatic intracerebral haemorrhage following thrombolysis for ischaemic stroke reports a median time to diagnosis of 470 minutes and highlights a role for cryoprecipitate in reversing recombinant tissue plasminogen activator coagulopathy.

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

Revised SPC: Fibrogamin (blood coagulation factor XIII) 250/1250IU

electronic Medicines Compendium

Fibrogammin is now licensed for use in paediatric patients. The initial dose in congenital Factor XIII deficiency has been increased to 40 units per kg every 28 days, in both adult and paediatric patients.

Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study

British Medical Journal

This large retrospective study found patients taking PPIs in addition to NSAID plus antithrombotics after MI had a lower risk of GI bleeding vs NSAID plus antithrombotics without PPI (1.8 vs 2.1 events per 100 person years; HR 0.72 95% CI = 0.54 to 0.95).

FDA approves idarucizumab (Praxbind), the first reversal agent for the anticoagulant dabigatran (Pradaxa)

US Food and Drug Administration

In healthy volunteers (n=283) given idarucizumab there was an immediate reduction in the amount of unbound dabigatran plasma lasting at least 24 hours. In another trial (n=123) dabigatran was fully reversed in 89% of patients within four hours of receiving idarucizumab.

Acute coronary syndromes

British Medical Journal

This review provides a comprehensive account of the pathophysiology, clinical presentation, management, and outcomes of acute coronary syndrome.

Drug problems: Dangerous decision-making at the FDA

Project on Government Oversight

This independent report alleges that the US FDA lowered its standards to ease approval of dabigatran and then deflected questions about its safety that arose after the drug entered clinical practice.

US FDA approves first Factor X concentrate (Coagadex®) to treat patients with hereditary Factor X (10) deficiency

US Food and Drug Administration

Coagadex, which is derived from human plasma, is indicated for patients aged ≥12 years with hereditary Factor X deficiency for on-demand treatment and control of bleeding episodes, and for perioperative management of bleeding in patients with mild hereditary Factor X deficiency.

Left Atrial Appendage Occlusion Device and Novel Oral Anticoagulants Versus Warfarin for Stroke Prevention in Nonvalvular Atrial Fibrillation: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Circulation: Arrhythmia and Electrophysiology

Meta-analysis of 7 studies found stroke prevention with NOACs is superior to warfarin in patients with nonvalvular atrial fibrillation; and the Watchman left atrial appendage occlusion device was considered a reasonable noninferior alternative 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

Revised SPC: Eliquis (apixaban) film-coated tablets

electronic Medicines Compendium

Information regarding the use of alternative methods of administration of apixaban tablets (crushed tablets) has been added to sections 4.2 and 5.2. Recommendations on use of prothrombin complex concentrates to reverse its anticoagulant effect have been added to 4.9.

Riociguat (Adempas®) for chronic thromboembolic pulmonary hypertension

All Wales Medicines Strategy Group

Riociguat is recommended for use in NHS Wales for treatment of adults with WHO class II- III inoperable chronic thromboembolic pulmonary hypertension (CTEPH); or persistent or recurrent CTEPH after surgical treatment to improve exercise capacity providing PAS is utilised.

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

Efficacy and safety of ticagrelor for long-term secondary prevention of atherothrombotic events in relation to renal function: insights from the PEGASUS-TIMI 54 trial

European Heart Journal

Although the relative benefits of ticagrelor were similar in patients with reduced renal function (eGFR<60mL/min), absolute benefits were higher as their risk of major adverse CV events was higher. There was however an excess of minor bleeding events.

Cardiovascular Management in Pregnancy: Antithrombotic Agents and Antiplatelet Agents

Circulation

This article reviews the use of anticoagulants and antiplatelets during pregnancy and highlights their clinical utility in conditions including VTE, thrombophilias, mechanical heart valves, APLS, pre-eclampsia, intrauterine growth restriction, and placental abruption.

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

The Clots in Legs Or sTockings after Stroke (CLOTS) 3 trial: a randomised controlled trial to determine whether or not intermittent pneumatic compression reduces the risk of post-stroke deep vein thrombosis and to estimate its cost-effectiveness

National Institute for Health Research

In immobile patients with stroke, use of intermittent pneumatic compression (IPC) was associated with a reduced incidence of DVT within 30 days of randomisation (8.5% vs 12.1% with no IPC, absolute reduction in risk of 3.6%; estimated cost of £1,282 per event prevented).

Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians

Annals of Internal Medicine

This report presents an evidence-based and high-value diagnostic strategy for the diagnosis of pulmonary embolism, to help clinicians understand the potential hurdles to such an approach and outline performance improvement strategies to overcome them.

Sulodexide for the Prevention of Recurrent Venous Thromboembolism: The SURVET Study: A Multicenter, Randomized, Double-Blind, Placebo Controlled Trial

Circulation

In this study, the use of sulodexide following discontinuation of anticoagulant therapy in patients with a first unprovoked VTE reduced the incidence of VTE recurrence (15/307 versus 30/308 with placebo; HR 0.49, 95% CI 0.27-0.92; P=0.025); adverse events were similar.

Bivalirudin versus unfractionated heparin: a meta-analysis of patients receiving percutaneous coronary intervention for acute coronary syndromes

Open Heart

Meta-analysis of 19 trials (n=35,596) found that bivalirudin increases risk of acute stent thrombosis (ST) in STEMI, but may confer an advantage over unfractionated heparin in NSTE- acute coronary syndromes while undergoing PCI, reducing major bleeding without an increase in ST.

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

European CHMP recommends granting of marketing authorisation for idarucizuma (Praxbind) as antidote to dabigatran

European Medicines Agency

Idarucizuma is a specific reversal agent for dabigatran and is intended for use in adults when rapid reversal is required for emergency surgery/urgent procedures; or in life-threatening or uncontrolled bleeding. It is proposed that use be restricted to hospital only.

Edoxaban for preventing stroke and systemic embolism in people with non valvular atrial fibrillation – guidance (TA355)

National Institute for Health and Care Excellence

NICE recommends the use of edoxaban as an option for preventing stroke and systemic embolism in adults with non-valvular atrial fibrillation with one or more risk factors. The decision about whether to start treatment with edoxaban should be made after an informed discussion.

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

An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers, Editor’s Capsule Summary

Annals of Emergency Medicine

Study (n=243) found bleeding after ingestion of Xa inhibitor is uncommon. Prothrombin time, APTT, or INR may be elevated in minority of cases but appears unreliable to measure bleeding risk. Massive acute ingestion in suicides may result in significant anticoagulation.

Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis

Open Heart

Meta-analysis of 39 studies suggests that the controversial interaction between PPIs and clopidogrel seen in in-vitro studies has no clinical significance. Rather, patients on PPIs have higher burden of comorbidities and thus most likely have increased risk for adverse CV events.

FDA approves recombinant Factor VIII (Nuwiq®) for the treatment of Haemophilia A

Biospace Inc.

The FDA has approved Nuwiq® for the treatment of adults and children with Haemophilia A. This is the first B-domain deleted recombinant Factor VIII derived from a human cell-line, not chemically modified or fused with another protein, designed for the treatment of this population.

Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke

Cochrane Database of Systematic Reviews

Risk was only increased in women using COCs containing ≥ 50 µg of estrogen. When combined with results of studies on risk of venous thrombosis in COC users, it seems that the COC pill containing levonorgestrel and 30 µg of estrogen is safest oral form of hormonal contraception.

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

Diagnostic prediction models for suspected pulmonary embolism: systematic review and independent external validation in primary care

British Medical Journal

Five diagnostic prediction models to rule out PE were evaluated for transportability to primary care in a cohort of 598 patients. Although efficiency was similar (43-48%), the three Wells rules performed better than the revised Geneva models for safety (failure rate 1.2% v 3.1%).

The CHA2DS2-VASc score for stroke risk stratification in patients with atrial fibrillation: a brief history

European Heart Journal

The CHA2DS2-VASc score is now recommended in many guidelines for stroke risk stratification in AF. The article discusses the evolution of this scoring system.

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

Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials

European Heart Journal

In high-risk patients with prior MI, dual antiplatelet therapy (DAPT) for >1 year decreased the risk of major adverse cardiovascular events and CV death versus aspirin alone, with no difference in overall mortality. Major bleeding, but not fatal bleeding, was increased with DAPT.

Strategies for thromboprophylaxis in Fontan circulation: a meta-analysis

Heart

his meta-analysis of 10 studies (n=1,200) found aspirin or warfarin prophylaxis reduced the risk of thromboembolic events in patients who underwent the Fontan procedure; there was no significant difference between the two agents.

A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan

European Heart Journal

The Absorb bioresorbable vascular scaffold was deemed non-inferior to cobalt-chromium everolimus-eluting stents in terms of target lesion failure at 12 months (incidence of 4.2% vs 3.8%, respectively) in patients with one or two de novo lesions in different epicardial vessels.

Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes

New England Journal of Medicine

In patients with ACS for whom PCI was anticipated, bivalirudin was associated with a similar rate of major adverse CV events to unfractionated heparin (10.3% v 10.9%; RR 0.94; 95% CI 0.81 to 1.09; P=0.44). A post-PCI bivalirudin infusion did not appear to be of any benefit.

How to Monitor Patients Receiving Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation

Annals of Internal Medicine

This evidence-based practice tool, endorsed by Thrombosis Canada, the Canadian Stroke Consortium, the Canadian Cardiovascular Pharmacists Network and the Canadian Cardiovascular Society, aims to help healthcare professionals provide best-practice anticoagulant follow-up care.

XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation

European Heart Journal

This study investigating the safety and efficacy of rivaroxaban in routine clinical use reported that rates of stroke and major bleeding were low in patients receiving rivaroxaban in routine clinical practice (0.7 and 2.1 events per 100 patient-years respectively).

The Efficacy and Safety of Vorapaxar With and Without a Thienopyridine for Secondary Prevention in Patients with Prior Myocardial Infarction and no History of Stroke or TIA: Results from TRA 2 P-TIMI 50

Circulation

Pre-specified analysis (n=16,897) found vorapaxar (VX) significantly reduced composite of CV death, MI and stroke vs. placebo, regardless of planned thienopyridine (TP) therapy. Moderate/severe bleeding risk was increased with VX and was not significantly altered by planned TP.

Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study

European Heart Journal

Retrospective study (n=2244) found discontinuation of platelet inhibitor 3 days before surgery, as opposed to 5 days, did not increase the incidence of major bleeding complications in ticagrelor-treated patients, but increased the incidence in clopidogrel-treated patients.

Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation

Journal of the American Medical Association

Cohort study (n=42,987) found that among patients with incident heart failure with/without AF, CHA2DS2-VASc score was linked to risk of ischaemic stroke, thromboembolism, and death. However, predictive accuracy was modest and clinical utility of score remains to be determined.

Effect of clopidogrel with aspirin on functional outcome in TIA or minor stroke: CHANCE substudy

Neurology

This subgroup analysis suggests that clopidogrel plus aspirin vs. aspirin alone improves 90-day functional outcome (poor functional outcome occurred in 254 [9.9%] on combination vs 299 [11.6%] on aspirin alone; p=0.046) in patients with acute minor stroke or TIA.

Bispecific antibody ACE910 assigned ‘breakthrough’ designation in US for prophylactic treatment of haemophilia A patients who have developed factor VIII inhibitors

PharmaTimes

ACE910 is an investigational humanised bispecific monoclonal antibody engineered to mimic the function of blood coagulation factor VIII, and thus provide a new approach to treating the condition, regardless of whether patients have developed inhibitors.

Ticagrelor approved in US for long-term use in patients with acute coronary syndrome or a history of myocardial infarction

PharmaTimes

FDA approval of long term use is based on data from PEGASUS TIMI-54 study, which showed that in patients on aspirin with MI more than 1 year previously, treatment with ticagrelor significantly reduced risk of CV death, MI, or stroke (but increased risk of major 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

Edoxaban for treating and for preventing deep vein thrombosis and pulmonary embolism – guidance (TA354)

National Institute for Health and Care Excellence
NICE recommends edoxaban, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults.

Medication Initiation Burden Required to Comply with Heart Failure Guideline Recommendations and Hospital Quality Measures

Circulation

This US-based study (n=158,992; 271 hospitals) suggests 22% of patients admitted for HF require initiation of at least 1 medicine; research into benefits of mass initiation of medications prior to discharge v sequential initiation extending into the ambulatory setting is needed.

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