Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease

Journal of the American College of Cardiology

Meta-analysis of 4 RCTs noted that in this population without moderate/severe mitral stenosis/mechanical heart valves, NOACs seem attractive alternatives to vitamin K antagonists because coexistence of valvular heart disease does not affect overall relative efficacy/safety.


Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes


Paper reports that long-term bleeding risk during dual antiplatelet therapy (DAPT) for patients with ACS can be reliably predicted with selected baseline characteristics using TRILOGY ACS bleeding risk models thus informing risk–benefit considerations regarding DAPT duration.


Stability of repackaged dabigatran etexilate capsules in dose administration aids

European Journal of Hospital Pharmacy

Study reports storage of capsules at ambient conditions for 14 and 28 days resulted in % drug remaining of 92.5% and 71.6%, respectively. In contrast, repackaged capsules stored in fridge for 28 days had drug content of 98.2% and dissolution was not significantly affected.



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Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies

European Heart Journal

Data from observational cohort studies suggest beneficial effect of statin on venous thromboembolism recurrence. In pooled analysis of 7 trials, relative risk (RR) was 0.73 (0.68–0.79) vs. no use. RRs for recurrent PE and DVT were 0.75(0.58–0.96) and 0.66 (0.60–0.71) respectively.


FDA fast track designation granted for recombinant ADAMTS13 for treatment of hereditary thrombotic thrombocytopenic purpura

Biospace Inc.

Recombinant ADAMTS13 is intended for treatment of acute episodes of hereditary thrombotic thrombocytopenic purpura in patients with a constitutional deficiency of the von Willebrand factor-cleaving protease ADAMTS13. Shire is initiating open-label, 2-period crossover RCT.


Should we screen extensively for cancer after unprovoked venous thrombosis?

British Medical Journal

Prevalence of occult cancer in patients with 1st unprovoked venous thromboembolism seems to be lower (~4%) than previously reported (10%). Review notes high quality data from recently completed trials suggest no additional value for extensive screening strategies.


Risk of myocardial infarction in patients with atrial fibrillation using vitamin K antagonists, aspirin or direct acting oral anticoagulants

British Journal of Clinical Pharmacology

Real-life cohort study (n=30146) suggests risk of acute myocardial infarction was doubled with direct oral anticoagulants or aspirin vs. vitamin k antagonists (HR 2.11; 95% CI 1.08 – 4.12 and 1.91; 1.45-2.51, respectively). Further research from is required.


Two Paradigms for Endovascular Thrombectomy After Intravenous Thrombolysis for Acute Ischemic Stroke

JAMA Neurology

French study of 159 patients ultimately treated by mechanical thrombectomy, of which 100 received IV thrombolysis before transport to a more fully equipped hospital, and 59 did not, found no difference in functional independence at 3 months after stroke between the 2 groups.


Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

New England Journal of Medicine

RCT of 3365 patients randomised after 6-12months anticoagulant therapy found symptomatic recurrent fatal/nonfatal venous thromboembolism occurred in 1.5% patients given 20 mg and 1.2% given 10 mg rivaroxaban, vs. 4.4% given aspirin (p<0.001 vs. aspirin for both).


Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study

British Medical Journal

This validation study (n= 2785) of the HERDOO2 clinical assessment tool found that women with 0 or 1 of the 4 criteria have a low risk of recurrent venous thromboembolism and can safely discontinue anticoagulants after completing short term treatment.


Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation

New England Journal of Medicine

The RE-CIRCUIT trial (n= 704) found that the incidence of major bleeding events after ablation was lower with dabigatran versus warfarin in patients with atrial fibrillation (1.6% vs 6.9%; absolute risk difference, −5.3%; 95% CI, −8.4 to −2.2; P<0.001).


Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial

The Lancet

RCT (n= 3,037) found that low-dose rivaroxaban with a P2Y12 inhibitor (clopidogrel or ticagrelor) had a similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes (5% both groups).


Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study

The Lancet

Registry data analysis found that leaflet thrombosis was less frequently observed in patients using warfarin or novel oral anticoagulants (eight [4%] of 224) than in those using dual antiplatelet or monoantiplatelet therapy (98 [15%] of 666; p<0•0001).



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Interruption to antiplatelet therapy early after acute ischaemic stroke: A nested case-control study

British Journal of Clinical Pharmacology

Study of 194 cases and 776 matched controls, of whom 10 and 58, respectively, stopped/interrupted antiplatelets found no significant link between interrupted/cessation of use and risk of CV events, though study had limited power and clinically important risk cannot be excluded.


2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines


Several RCTs have been published since 2014 guideline. Major areas of change include indications for transcatheter aortic valve replacement, surgical management of primary/secondary mitral regurgitation, and management of patients with valve prostheses.


Efficacy and safety of extended thromboprophylaxis for medically ill patients. A meta-analysis of randomised controlled trials

Thrombosis and Haemostasis

Review of 4 RCTs (n=28,105) found that extended thromboprophylaxis was associated with a lower risk of DVT though PE and VTE related mortality differences were not significant. The NNT for DVT prevention was 339, with a NNH for major bleed as 247.


Association of Preceding Antithrombotic Treatment With Acute Ischemic Stroke Severity and In-Hospital Outcomes Among Patients With Atrial Fibrillation

Journal of the American Medical Association

A study of 94,474 patients with acute ischemic stroke and AF found that 84% did not receive guideline-recommended therapeutic anticoagulation preceding the stroke. Therapeutic anticoagulation was associated with lesser stroke severity and lower odds of in-hospital mortality.


Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism

Cochrane Database of Systematic Reviews

Moderate-level data suggest that fixed dose LMWH reduced incidence of recurrent thrombotic complications and occurrence of major haemorrhage during initial treatment; and low-quality data suggest fixed dose LMWH reduced thrombus size vs UFH for the initial treatment of VTE.


Early non-persistence with dabigatran and rivaroxaban in patients with atrial fibrillation


Study (n=25,976) found at 6 months, 36.4 and 31.9% of patients were non-persistent to dabigatran and rivaroxaban, respectively. Stroke/TIA/death was higher with non-persistence vs. persistence (HR 1.76, 95% CI 1.60-1.94 and 1.89, 1.64-2.19; p<0.0001 for both, respectively).



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Subcutaneous unfractionated heparin for the initial treatment of venous thromboembolism

Cochrane Database of Systematic Reviews

This review of 16 RCTs (n=3593; general low quality) concludes that there is no evidence of a difference between subcutaneous unfractionated heparin (UFH) and intravenous UFH or subcutaneous low molecular weight heparin for preventing recurrent clots, mortality or major bleeding.


Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis

National Institute for Health Research

NOACs have advantages over warfarin in AF patients, but there was no strong evidence they should replace warfarin/low molecular weight heparin in primary prevention (PV), treatment or secondary PV of venous thromboembolism. Findings limited by lack of head to head NOAC studies.


Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials

The Lancet

This paper describes PRECISE-DAPT score, a simple 5-item risk score (age, creatinine clearance, haemoglobin, white-blood-cell count, previous spontaneous bleeding), which provides a standardised tool for prediction of out-of-hospital bleeding during dual antiplatelet therapy.


Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis

European Heart Journal

Review highlights that when compared with earlier systematic review, increased use of mechanical valves with lower thrombogenic potential has not necessarily resulted in lower risk of adverse outcomes, and optimal method of anticoagulation remains undetermined in this population.


Comparative effectiveness of venous thromboembolism prophylaxis options for the patient undergoing total hip and knee replacement: a network meta-analysis

Journal of Thrombosis and Haemastasis

Relative to low-molecular-weight heparin, direct oral Xa inhibitors had a more favorable profile of venous thromboembolism and haemorrhage risk, whereas vitamin K antagonists had a less favorable profile. The profile of other agents was not more or less favourable.


Pharmacokinetics and pharmacodynamics of single doses of rivaroxaban in obese patients prior to and after bariatric surgery

British Journal of Clinical Pharmacology

Analysis of 6 Roux-en-Y gastric bypass and 6 sleeve gastrectomy patients found bariatric surgery does not appear to alter pharmacokinetics of rivaroxaban in clinically relevant way. Effective prophylactic postbariatric anticoagulation is supported by changes in pharmacodynamics.



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Personalising the decision for prolonged dual antiplatelet therapy: development, validation and potential impact of prognostic models for cardiovascular events and bleeding in myocardial infarction survivors

European Heart Journal

This modelling study was developed from data taken from UK population-based electronic health records (n=12694 and 5613, respectively), and quantified the potential benefits and harms of prolonged dual antiplatelet therapy (DAPT) in MI survivors.


Duration of dual antiplatelet therapy in acute coronary syndrome


Review notes it has been 15 years since CURE trial showed benefit of dual antiplatelet therapy following ACS and yet optimal duration remains uncertain. It highlights need for broad inclusive safety trial of shorter durations of therapy in real world populations of ACS patients.


Association of Antithrombotic Drug Use With Subdural Hematoma Risk

Journal of the American Medical Association

Study (10,010 patients, 400,380 controls) found antithrombotic use increased risk of subdural haematoma. Highest odds were associated with combined use of vitamin K antagonist+antiplatelet (aspirin or clopidogrel, OR 4.00, 95%CI 3.40-4.70, and 7.93, 4.49-14.02, respectively).



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Myocardial Infarction Risk after Discontinuation of Thienopyridine Therapy in the Randomized DAPT Study


Among 11,648 randomised patients, monthly cumulative incidence of MI was lower with continued thienopyridine vs. placebo at 12-15 months (0.12% vs. 0.37%, p<0.001) and higher at 30-33 months (0.30% vs. 0.15%, p=0.013). Majority of MIs were not related to stent thrombosis.


Real-life treatment of venous thromboembolism with direct oral anticoagulants: The influence of recommended dosing and regimens

Thrombosis and Haemostasis

Spanish registry study (n=1725) noted patients on DOACs at non-recommended doses and/or regimens experienced higher rate of venous thromboembolism recurrences (HR:10.5;95 %CI:1.28–85.9) and similar rate of major bleeding/death vs. those on recommended doses and regimens.


Effect of Fibrinogen Concentrate on Intraoperative Blood Loss Among Patients With Intraoperative Bleeding During High-Risk Cardiac Surgery: A Randomized Clinical Trial

Journal of the American Medical Association

RCT (n=120) found among patients with intraoperative bleeding during high-risk cardiac surgery, administration of IV single dose fibrinogen concentrate, vs.
placebo, resulted in no significant difference in the amount of intraoperative blood loss (50 vs. 70mL, respectively).


New product: FibCLOT 1.5 g. powder and solvent for solution for injection/infusion (human fibrinogen)

electronic Medicines Compendium

FibCLOT is licensed for the treatment and perioperative prophylaxis of bleeding in patients with congenital hypo- or afibrinogenaemia with bleeding tendency.


Outcomes Associated With Resuming Warfarin Treatment After Hemorrhagic Stroke or Traumatic Intracranial Hemorrhage in Patients With Atrial Fibrillation

JAMA Internal Medicine

Study of 2415 patients who experienced a traumatic intracranial haemorrhage (ICH) or haemorrhagic stroke (HS) showed resuming warfarin therapy was associated with lower rate of ischaemic stroke or systemic embolism. However, in those with HS, a high rate of ICH was observed.


Effects of dabigatran according to age in atrial fibrillation


Analysis (n=10855) found effects of dabigatran vs. warfarin on stroke prevention/intracranial bleeding were consistent across all ages. Effects of dabigatran on extracranial major bleeding were age dependent, supporting use of 110 mg BD dose for elderly patients (≥80 years).


Drug-induced liver injury (DILI) with oral anticoagulants: a threat or not?


This editorial discusses the background of DILI, highlighting that it can develop with the use of nearly any drug. It then goes on to discuss the current
evidence base for DILI with oral anticoagulants, reviewing the use of the newer drugs in liver impairment vs. warfarin.

Risk of major bleeding and stroke associated with the use of VKAs, NOACs and aspirin in patients with atrial fibrillation: a cohort study

British Journal of Clinical Pharmacology

Retrospective cohort study (n=31,497) found NOACs and vitamin K antagonists equally effective in preventing stroke but NOACs were linked to higher risk of GI bleeding (HR 2.63, 95% CI 1.50-4.62), particularly in women. Aspirin was not effective in prevention of stroke in AF.


Edoxaban for the Prevention of Thromboembolism in Patients with Atrial Fibrillation and Bioprosthetic Valves


191 patients in ENGAGE AF-TIMI 48 trial had bioprosthetic valves, of which those on higher-dose edoxaban (HDED) had similar rates of stroke/ systemic embolic events (S/SEE) and major bleeding (MB) vs warfarin. Patients on lower DED had similar rates of S/SEE but lower rates of MB.


Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European society of cardiology working groups of aorta and peripheral circulation and pulmonary circulation and right ventricular function

European Heart Journal

This covers diagnosis, initial (first 5–21 days) and long-term (first 3–6 months) phase management, extended phase management (beyond first 3–6 months), and special situations.


Postapproval Observational Studies of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation

Journal of the American Medical Association

Review notes that despite limitations of observational data about NOAC use for stroke prevention in AF, they do broadly confirm results of the pivotal NOAC
RCTs and show that these agents are viable alternatives to warfarin in routine clinical practice.


Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial

The Lancet Haematology

Study (n=435) reports primary outcome (composite of symptomatic DVT or PE, progression or recurrence of superficial vein-thrombosis, and all-cause
mortality at 45 days) occurred in 3% of those on rivaroxaban v 2% of those on fondaparinux (HR 1.9, p=0·0025 for non-inferiority).



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Management of Patients on Non–Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association


This statement reviews the literature and offers practical suggestions for providers who manage patients who are actively bleeding and who are at risk
for bleeding in the acute care and periprocedural setting.


Peri-Operative Management of Anticoagulation and Antiplatelet Therapy

British Society for Haematology

This guideline will consider whether and when anticoagulants and antiplatelet agents should be stopped before elective surgery and invasive procedures,
when agents can be restarted and how to manage patients on these drugs who require emergency surgery.


Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study

British Medical Journal

Study (n=55,644) found no significant difference (SD) vs. warfarin (WF) in ischaemic stroke/systemic embolism rates with apixaban (AP) 2.5mg or in
thromboembolic rates with dabigatran (DB) 110mg and rivaroxaban (RV) 15mg. There was no SD in bleeding rates between AP and RV vs. WF



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Use of Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) Before Stroke

European Heart Journal

Analysis of registry data on 42,887 ischaemic stroke patients (251 on NOACs; 1500 on warfarin before stroke) treated with intravenous rt-PA within 4.5 hours found no significant difference in symptomatic intracranial haemorrhage in anticoagulated(AC'd) vs. non-AC'd patients.


Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin


RCT (n=270) found lower proportion of patients on PPI developed recurrent upper GI bleeding (0.7 v 3.1%) and reached composite end point of recurrent
bleeding/endoscopic ulcers at month 12 (7.9 vs. 12.4%) vs. H2 antagonist group, but difference was not statistically significant.


Individualized venous thromboembolism risk using the 2005 Caprini score to identify the benefits and harms of chemoprophylaxis in surgical patients: a meta-analysis

Annals of Surgery

This analysis of 13 studies (n=14,776) concludes benefit of peri-operative VTE chemoprophylaxis was only found among surgical patients with Caprini scores
≥7. Patients with scores ≤6 comprised 75% of overall population and did not show a VTE risk reduction with chemoprophylaxis.


Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy

Cochrane Database of Systematic Reviews

This updated review confirms that primary thromboprophylaxis with low molecular weight heparins significantly reduces the incidence of symptomatic venous
thromboembolism in ambulatory cancer patients treated with chemotherapy.



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Revised SPC: Dipyridamole 50mg/5ml Oral Suspension

electronic Medicines Compendium

Angina pectoris, post procedural haemorrhage and operative haemorrhage have been added as adverse reactions of dipyridamole.


Revised SPC: Nebido (testosterone undecanoate) 1000mg/4ml, solution for injection

electronic Medicines Compendium

Section 4.4 of SPC now includes warning that testosterone should be used with caution in patients with thrombophilia, as there have been post-marketing studies and reports of thrombotic events in these patients during testosterone therapy.


Direct-acting antivirals to treat chronic hepatitis C: risk of interaction with vitamin K antagonists and changes in INR

Medicines and Healthcare products Regulatory Agency

It is advised that INR should be monitored closely during treatment of chronic hepatitis C with direct-acting antivirals in patients also receiving vitamin
K antagonists (e.g. warfarin), because of possible changes in liver function during treatment.


Incidence of venous thromboembolism in care homes: a prospective cohort study

British Journal of General Practice

During a mean follow-up period of 312 days, this observational cohort study (n=1011) reports an increased incidence of venous thromboembolism in care homes compared to the community setting in people aged over 70 years.


Valvular heart disease and pregnancy part II: management of prosthetic valves


This is a review of pregnancy risks in women with prosthetic heart valves, strategies for anticoagulation in women with mechanical heart valves, and the management of complications.



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